Effectiveness of BBT-I and Zopiclone for Chronic Insomnia

• ClinicalTrials.gov Identifier: NCT03339583
• Recruitment Status: Completed
• First Posted: November 13, 2017
• Results First Posted: June 17, 2019
• Last Update Posted: September 16, 2019
• Sponsor: I.M. Sechenov First Moscow State Medical University
• Information provided by (Responsible Party): Polina Pchelina, I.M. Sechenov First Moscow State Medical University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Insomnia Chronic
• Interventions: Behavioral: Brief behavioral therapy; Drug: Zopiclone
• Enrollment: 42

Participant Flow

Recruitment Details
Pre-assignment Details	The decision to recruit more patients than it was stated in protocol was made because of dropout of 3 patients and in order to get enough experimental data to provide statistical power

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Period Title: First Intervention (14 Days)
Started	19	23
Completed	18	23
Not Completed	1	0
Reason Not Completed
Adverse Event	1	0
Period Title: Washout (14 Days)
Started	18	23
Completed	18	23
Not Completed	0	0
Period Title: Second Intervention (14 Days)
Started	18	23
Completed	18	21
Not Completed	0	2
Reason Not Completed
unrelated acute exacerbation	0	1
Adverse Event	0	1
Period Title: Follow-up (14 Days)
Started	18	21
Completed	12	18
Not Completed	6	3
Reason Not Completed
Physician Decision	6	3

Baseline Characteristics

Arm/Group Title		Zopiclone First Group	BBT-I First Group	Total
Arm/Group Description		underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	Total of all reporting groups
Overall Number of Baseline Participants		19	23	42
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	23 participants	42 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	13 68.4%	20 87.0%	33 78.6%
	>=65 years	6 31.6%	3 13.0%	9 21.4%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	19 participants	23 participants	42 participants
		55.0 (14.8)	47.5 (14.1)	50.7 (14.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	19 participants	23 participants	42 participants
	Female	11 57.9%	16 69.6%	27 64.3%
	Male	8 42.1%	7 30.4%	15 35.7%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants	0 participants	0 participants
				0
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
Russia	Number Analyzed	19 participants	23 participants	42 participants
		19 100.0%	23 100.0%	42 100.0%
Beck depression inventory [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		10.8 (5.0)	12.8 (7.2)	12.1 (6.1)
		[1] Measure Description: 0-63 scores. higher values represent worse outcome
State anxiety inventory [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		43.5 (8.7)	46.9 (6.9)	45.3 (8.1)
		[1] Measure Description: 0-80 scores. higher values represent worse outcome
trait anxiety inventory [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		49.6 (8.3)	49.1 (7.2)	49.3 (7.5)
		[1] Measure Description: 0-80 scores. higher values represent worse outcome
Dysfunctional beliefs about sleep scale [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		105.3 (28.7)	104.9 (30.2)	105.1 (27.2)
		[1] Measure Description: Measure Description: 0-160 scores. higher values represent worse outcome
Sleep hygiene index [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		26.7 (6.3)	28.7 (7.3)	27.9 (6.1)
		[1] Measure Description: Measure Description: 0-65 scores. higher values represent worse outcome
Insomnia severity index [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		18.7 (4.1)	17.5 (5.4)	18.6 (4.6)
		[1] Measure Description: 0-28 scores. higher values represent worse outcome
Pittsburgh sleep quality index [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		13.3 (3.5)	14.5 (2.7)	14.0 (3.1)
		[1] Measure Description: Measure Description: 0-24 scores. higher values represent worse outcome
Toronto Alexithymia scale-20 [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	19 participants	23 participants	42 participants
		49.8 (15.9)	49.3 (10.0)	49.5 (12.9)
		[1] Measure Description: Measure Description: 0-100 scores. higher values represent worse outcome
Sleep efficiency [1]; Mean (Standard Deviation); Unit of measure: Percentage of polysomnogram time
	Number Analyzed	19 participants	23 participants	42 participants
		64.68 (17.9)	63.3 (18.0)	63.9 (17.7)
		[1] Measure Description: derived from 1-night polysomnography at baseline
sleep latency [1]; Mean (Standard Deviation); Unit of measure: Minutes
	Number Analyzed	19 participants	23 participants	42 participants
		38.5 (21.7)	54.5 (51.0)	47.0 (40.2)
		[1] Measure Description: derived from 1-night polysomnography
Wake after sleep onset [1]; Mean (Standard Deviation); Unit of measure: Minutes
	Number Analyzed	19 participants	23 participants	42 participants
		102.4 (69.0)	104.8 (76.1)	103.6 (71.9)
		[1] Measure Description: derived from 1-night polysomnography
Awakenings [1]; Mean (Standard Deviation); Unit of measure: Awakenings
	Number Analyzed	19 participants	23 participants	42 participants
		13.8 (6.1)	13.3 (6.9)	13.5 (6.5)
		[1] Measure Description: derived from 1-night polysomnography
N1 NREM sleep percentage [1]; Mean (Standard Deviation); Unit of measure: Percentage of time
	Number Analyzed	19 participants	23 participants	42 participants
		4.2 (3.1)	3.7 (3.3)	3.9 (3.2)
		[1] Measure Description: derived from 1-night polysomnography
N2 NREM sleep percentage [1]; Mean (Standard Deviation); Unit of measure: Percentage of time
	Number Analyzed	19 participants	23 participants	42 participants
		64.2 (10.2)	62.6 (8.4)	63.3 (9.2)
		[1] Measure Description: derived from 1-night polysomnography
N3 NREM sleep percentage [1]; Mean (Standard Deviation); Unit of measure: Percentage of time
	Number Analyzed	19 participants	23 participants	42 participants
		17.5 (8.8)	16.4 (7.0)	16.9 (7.8)
		[1] Measure Description: derived from 1-night polysomnography
REM sleep percentage [1]; Mean (Standard Deviation); Unit of measure: Percentage of time
	Number Analyzed	19 participants	23 participants	42 participants
		14.1 (5.5)	17.0 (7.7)	15.6 (6.8)
		[1] Measure Description: derived from 1-night polysomnography
Total sleep time [1]; Mean (Standard Deviation); Unit of measure: Hours
	Number Analyzed	19 participants	23 participants	42 participants
		5.7 (1.6)	5.5 (1.6)	5.6 (1.6)
		[1] Measure Description: derived from 1-night polysomnography

Outcome Measures

1. Primary Outcome

Title	Insomnia Severity Index
Description	self reported insomnia symptoms severity by Insomnia severity index . Each item is scored 0 (no problem) - 4 (very big problem) with total between 0-28 (absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).
Time Frame	For BBT-I-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For zopiclone-first group: after washout period (Day 28/Week 4/Month 1) after second treatment course (Day 42/Week 6/Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		18.6 (5.2)	18.9 (3.9)
First treatment course	Number Analyzed	23 participants	19 participants
		13.1 (5.2)	14.0 (5.7)
After washout	Number Analyzed	23 participants	18 participants
		14.3 (6.3)	16.1 (4.7)
Second treatment course	Number Analyzed	21 participants	18 participants
		12.1 (6.1)	12.8 (5.4)
After follow-up	Number Analyzed	18 participants	12 participants
		13.1 (4.7)	12.7 (5.9)

2. Secondary Outcome

Title	Beck Depression Inventory
Description	21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week. Minimum score 0, maximum score 63 points. Higher total score represents more severe depressive symptoms
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		11.5 (6.8)	9.3 (7.3)
first treatment course	Number Analyzed	23 participants	19 participants
		8.4 (6.8)	9.4 (8.2)
After washout	Number Analyzed	23 participants	18 participants
		8.4 (8.2)	9.8 (5.1)
Second treatment course	Number Analyzed	23 participants	18 participants
		9.2 (9.0)	8.5 (6.2)
After follow-up	Number Analyzed	18 participants	12 participants
		9.0 (8.1)	7.4 (6.2)

3. Secondary Outcome

Title	State Anxiety Subscale (STAI)
Description	State trait anxiety scale is a 2-part questionnaire assessing state (situational) and trait anxiety. State anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		45.1 (8.8)	43.2 (8.5)
First treatment course	Number Analyzed	23 participants	19 participants
		43.8 (8.6)	44.3 (9.1)
After washout	Number Analyzed	23 participants	18 participants
		45.5 (9.0)	44.5 (9.8)
Second treatment course	Number Analyzed	23 participants	18 participants
		45.1 (9.1)	44.0 (9.6)
After follow-up	Number Analyzed	18 participants	12 participants
		46.9 (6.5)	44.2 (10.4)

4. Secondary Outcome

Title	Dysfunctional Beliefs About Sleep Scale
Description	questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale. Minimum score is 0, maximum score is 160 points. Higher total score represents more intensive disfunctional beliefs
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		105.2 (29.0)	93.2 (35.0)
First treatment course	Number Analyzed	23 participants	19 participants
		83.8 (34.8)	96.4 (36.4)
After washout	Number Analyzed	23 participants	18 participants
		84.76 (36.9)	103.6 (32.2)
Second treatment course	Number Analyzed	23 participants	18 participants
		84.5 (39.8)	89.2 (35.4)
After follow-up	Number Analyzed	18 participants	12 participants
		62.8 (34.5)	92.0 (34.5)

5. Secondary Outcome

Title	Sleep Hygiene Index
Description	questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.Minimum score 13 points and maximum score 65 points. Higher total score represents worse sleep hygiene
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		26.8 (7.4)	25.2 (5.9)
First treatment course	Number Analyzed	23 participants	19 participants
		24.0 (5.6)	25.0 (6.9)
After washout	Number Analyzed	23 participants	18 participants
		24.7 (6.0)	25.5 (7.4)
Second treatment course	Number Analyzed	23 participants	18 participants
		24.7 (6.6)	24.3 (6.6)
After follow-up	Number Analyzed	18 participants	12 participants
		23.8 (6.5)	25.2 (7.6)

6. Secondary Outcome

Title	Pittsburgh Sleep Quality Index
Description	19-item questionnaire evaluating sleep quality over the past month. The first 4 items are open questions, items 5 to 19 are rated on a 4-point Likert scale. A total score range from 0 to 21. A score > 5 suggests poor sleep quality.
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		13.4 (3.6)	11.9 (4.1)
First treatment course	Number Analyzed	23 participants	19 participants
		10.5 (4.5)	11.3 (4.1)
After washout	Number Analyzed	23 participants	18 participants
		11.3 (4.4)	12.7 (3.8)
Second treatment course	Number Analyzed	23 participants	18 participants
		10.8 (4.4)	11.7 (4.8)
After follow-up	Number Analyzed	18 participants	12 participants
		11.2 (4.9)	11.1 (4.7)

7. Secondary Outcome

Title	Trait Anxiety Subscale (STAI)
Description	STAI is a 2-part questionnaire assessing state (situational) and trait anxiety. Trait anxiety subscale comprise 20 items rated on a 4-point Likert scale. Minimum score for each subscale is 20 and maximum score is 80 points. Higher total score indicates more severe anxiety symptoms
Time Frame	on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/ Month 1), after washout period (Day 28/ Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 8), after second washout (Day 56/Week 8/ Month 2)

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title		BBT-I First Group	Zopiclone First Group
Arm/Group Description:		received two-week brief behavioral therapy followed by medication therapy (zopiclone). Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks	underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off. Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
Overall Number of Participants Analyzed		23	19
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline/initial examination	Number Analyzed	23 participants	19 participants
		48.7 (6.9)	48.3 (8.1)
First treatment course	Number Analyzed	23 participants	19 participants
		48.3 (8.1)	48.3 (8.6)
After washout	Number Analyzed	23 participants	18 participants
		48.6 (7.6)	49.3 (7.0)
Second treatment course	Number Analyzed	23 participants	18 participants
		46.3 (9.5)	48.5 (8.3)
After follow-up	Number Analyzed	18 participants	13 participants
		46.3 (8.6)	48.8 (10.7)

8. Other Pre-specified Outcome

Title	Toronto Alexithymia Scale (TAS-20)
Description	Degree of alexithymia evaluated by Toronto Alexithymia scale (20 questions) Measure Description: 0-100 scores. higher values represent worse outcome
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: scores on a scale
	49.83 (15.9)	49.33 (10.0)

9. Other Pre-specified Outcome

Title	Sleep Latency
Description	time period from bedding to sleep onset
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

Participants dropped out during the first treatment course and therefore not completed the second treatment course were included only in the analysis for first treatment course and were not analyzed for treatment sequence effect

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: minutes
	38.53 (21.7)	54.5 (51.0)

10. Other Pre-specified Outcome

Title	Total Sleep Time
Description	total sleep episode minus wake time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

Analysis included all randomized participants

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: hours
	5.72 (1.6)	5.51 (1.6)

11. Other Pre-specified Outcome

Title	Sleep Efficiency
Description	Prercentage of Total Bed Time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

Analysis included all participants who were randomized and filled set of questionnaires at baseline assessment

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: percentage of polysomnogram time
	64.68 (17.9)	63.29 (18.0)

12. Other Pre-specified Outcome

Title	Wake After Sleep Onset
Description	total duration of all periods of wakefulness between sleep onset and final awakening in the morning
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: minutes
	102.39 (69.0)	104.75 (76.1)

13. Other Pre-specified Outcome

Title	Amount of Awakenings
Description	Number of awakenings between sleep onset and final morning awakening
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: awakenings
	13.78 (6.1)	13.25 (6.9)

14. Other Pre-specified Outcome

Title	N1 NREM Sleep Percentage
Description	Percentage of Total Sleep Time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: percentage of total sleep time
	4.16 (3.1)	3.70 (3.3)

15. Other Pre-specified Outcome

Title	N2 NREM Sleep Percentage
Description	Percentage of Total Sleep Time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: percentage of time
	64.19 (10.2)	62.58 (8.4)

16. Other Pre-specified Outcome

Title	N3 NREM Sleep Percentage
Description	Percentage of Total Sleep Time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: percentage of total sleep time
	17.52 (8.8)	16.39 (7.0)

17. Other Pre-specified Outcome

Title	REM Sleep Percentage
Description	Percentage of Total Sleep Time
Time Frame	once at baseline assessment

Outcome Measure Data

Analysis Population Description

All randomised participants who filled baseline set of questionnaires

Arm/Group Title	Zopiclone First, Then BBT-I	BBT-I First, Then Zopiclone
Arm/Group Description:	Participants first received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. After a washout of two weeks they then received Brief behavioral therapy program for two weeks in two weekly individual sessions. Then they completed follow-up for two weeks	Participants first received Brief behavioral therapy program for two weeks in two weekly individual sessions. After a washout of two weeks they then received zopiclone in a dose of 7.5 mg 30 minutes before bedtime for two weeks. Then they completed follow-up for two weeks
Overall Number of Participants Analyzed	19	23
Mean (Standard Deviation); Unit of Measure: percentage of total sleep time
	14.1 (5.5)	17.0 (7.7)

Adverse Events

Time Frame	2 months
Adverse Event Reporting Description	Adverse effects were evaluated systematically during biweekly visits
Arm/Group Title	BBT-I		Zopiclone
Arm/Group Description	Brief behavioral therapy: program included a question-and-answer part; a didactic presentation of sleep regulation mechanisms; the review of causes of onset and chronification of illness; an examination of patient's sleep log; explanation of sleep restriction method and prescription of individual regimen of sleep; explanation of stimulus control method; sleep hygiene education; discussion of relaxation techniques. Participants were supplied with 32 minute audio recording "Relaxation and refreshment session for insomnia" created for this study by Dr. A.Tabidze with verbal relaxing instructions with quiet musical composition behind it. Participants were instructed to listen to this recording in headphones each day for 2-week BBT-I period after laying into bed and turning the light off.		Zopiclone: zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
All-Cause Mortality
	BBT-I		Zopiclone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/42 (0.00%)		0/41 (0.00%)
Serious Adverse Events
	BBT-I		Zopiclone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0.00%)		0/41 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	BBT-I		Zopiclone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/42 (0.00%)		2/41 (4.88%)
Hepatobiliary disorders
bitter taste *	0/42 (0.00%)	0	1/41 (2.44%)	2
Skin and subcutaneous tissue disorders
rash hypersensitivity reaction to zopiclone *	0/42 (0.00%)	0	1/41 (2.44%)	2
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Polina Pchelina
• Organization: I.M. Sechenov First Moscow State Medical University
• Phone: +79036701725
• EMail: polbox@mail.ru

Publications of Results:

Pchelina PV, Tabidze AA, Poluektov MG. [Comparative study of effectiveness of cognitive-behavior therapy and zopiclone for chronic insomnia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2017;117(4. Vyp. 2):48-55. doi: 10.17116/jnevro20171174248-55. Russian.

• Responsible Party: Polina Pchelina, I.M. Sechenov First Moscow State Medical University
• ClinicalTrials.gov Identifier: NCT03339583
• Other Study ID Numbers: 1
• First Submitted: October 17, 2017
• First Posted: November 13, 2017
• Results First Submitted: March 11, 2018
• Results First Posted: June 17, 2019
• Last Update Posted: September 16, 2019