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

Tracking Information

• First Submitted Date: October 17, 2017
• First Posted Date: November 13, 2017
• Results First Submitted Date: March 11, 2018
• Results First Posted Date: June 17, 2019
• Last Update Posted Date: September 16, 2019
• Actual Study Start Date: April 7, 2015
• Actual Primary Completion Date: March 14, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2019)

Insomnia Severity Index [ 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) ]

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).

Original Primary Outcome Measures (submitted: November 9, 2017)

• Change of Insomnia Severity Index after BBT-I [ 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) ]
  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).
• Change of Insomnia Severity Index after zopiclone [ Time Frame: For zopiclone-first group: on the initial examination (Day 1/Week 1/Month 1), after first treatment course (Day 14/Week 2/Month 1); For BBT-I-first group after washout period (Day 28/Week 4/Month 1), after second treatment course (Day 42/Week 6/Month 2) ]
  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).

Current Secondary Outcome Measures (submitted: March 18, 2019)

• Beck Depression Inventory [ 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) ]
  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
• State Anxiety Subscale (STAI) [ 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) ]
  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
• Dysfunctional Beliefs About Sleep Scale [ 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) ]
  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
• Sleep Hygiene Index [ 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) ]
  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
• Pittsburgh Sleep Quality Index [ 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) ]
  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.
• Trait Anxiety Subscale (STAI) [ 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) ]
  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

Original Secondary Outcome Measures (submitted: November 9, 2017)

• Beck Depression Inventory [ 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) ]
  21-item questionnaire assessing (on 4-point Likert scales) the intensity of depressive symptoms in the past week
• State-trait anxiety inventory [ 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) ]
  2-part questionnaire assessing state (situational) and trait anxiety. Both situational and trait parts comprise 20 items rated on a 4-point Likert scale.
• Dysfunctional beliefs about sleep scale [ 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) ]
  questionnaire assessing sleep related cognitions in 16 item rated on a 10-point Likert scale.
• Sleep hygiene index [ 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) ]
  questionnaire assessing sleep related behavior in 13 item rated on a 5-point Likert scale.
• Pittsburgh Sleep Quality Index [ 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) ]
  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.
• Big Five Questionnaire [ Time Frame: once at baseline assessment ]
  questionnaire assessing personal traits in 134 item rated on a 5-point Likert scale.
• Objective sleep latency [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• Objective total sleep time [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• Objective sleep efficiency [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• Objective wake after sleep onset [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• Objective number of awakenings [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• Objective sleep stages proportion [ Time Frame: once at baseline assessment ]
  evaluated by polysomnography
• β-adrenoreactivity test [ 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) ]
  laboratory peripheral blood sample analysis for evaluation of sympathetic activity
• Toronto Alexithymia Scale - short version (TAS-20) [ Time Frame: once at baseline assessment ]
  questionnaire assessing alexithymia in 20 item rated on a 5-point Likert scale.
• Insomnia severity index [ 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) ]
  self reported insomnia symptoms severity . 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).

Current Other Pre-specified Outcome Measures (submitted: September 13, 2019)

• Toronto Alexithymia Scale (TAS-20) [ Time Frame: once at baseline assessment ]
  Degree of alexithymia evaluated by Toronto Alexithymia scale (20 questions) Measure Description: 0-100 scores. higher values represent worse outcome
• Sleep Latency [ Time Frame: once at baseline assessment ]
  time period from bedding to sleep onset
• Total Sleep Time [ Time Frame: once at baseline assessment ]
  total sleep episode minus wake time
• Sleep Efficiency [ Time Frame: once at baseline assessment ]
  Prercentage of Total Bed Time
• Wake After Sleep Onset [ Time Frame: once at baseline assessment ]
  total duration of all periods of wakefulness between sleep onset and final awakening in the morning
• Amount of Awakenings [ Time Frame: once at baseline assessment ]
  Number of awakenings between sleep onset and final morning awakening
• N1 NREM Sleep Percentage [ Time Frame: once at baseline assessment ]
  Percentage of Total Sleep Time
• N2 NREM Sleep Percentage [ Time Frame: once at baseline assessment ]
  Percentage of Total Sleep Time
• N3 NREM Sleep Percentage [ Time Frame: once at baseline assessment ]
  Percentage of Total Sleep Time
• REM Sleep Percentage [ Time Frame: once at baseline assessment ]
  Percentage of Total Sleep Time

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effectiveness of BBT-I and Zopiclone for Chronic Insomnia
• Official Title: Effectiveness of Nonspecific Methods of Treatment and Zopiclone for Chronic Insomnia

Brief Summary

Background: Importance of chronic insomnia (CI) problem is determined by its high prevalence rate, comorbidity and resistance to the treatment. Although cognitive behavior treatment of insomnia (CBT-I) remains the recommended treatment for CI it has disadvantages of time consuming and low treatment response. Hence shortened and simplified behavioral approaches such as Brief Behavioral therapy of insomnia (BBT-I) are developed. The aim of the present study is to test the effectiveness of BBT-I program for chronic insomnia in comparison with zopiclone in Russian population. The anthropometric, psychological and polysomnographic characteristics of patients were measured to find predictors of effectiveness of each method.

Participants: 42 adults (14 males, 28 females, mean age 54 years) meeting the criteria for CI according International classification of sleep disorders-3 Methods: Participants were randomized into two groups. Each group passed 2-week courses of treatment by brief behavior treatment of insomnia (BBT-I) and zopiclone in different orders with 2-week washout period between the courses. Participants underwent in-lab polysomnography prior to the treatment and completed questionnaires (Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Beck Depression Inventory (BDI) and others) in the beginning and the end of each course

Detailed Description

The study had a crossover design implying that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions.

Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect.

Before and after each treatment course and after each washout period subjects completed set of questionnaires.

The total duration of the study was 8 weeks in which 6 visits including 1 night polysomnography (PSG), 2 face-to-face structured educational program sessions and 5 diagnostic interviews have been performed.

Participants A sample of 42 adults (14 males, 28 females, mean age 54 years from 29 to 80 years) meeting the criteria for chronic insomnia according ICSD-3 was recruited from outpatient care of Department of sleep medicine of University Hospital №3 of I.M. Sechenov First Moscow State Medical University. All participants were informed about the nature, purpose, risks, and discomforts that could arise from their participation, and about their right to withdraw at any time. Subjects documented their willingness to participate by signing the informed consent form, approved by local Ethic Committee.

Treatment methods. BBT-I program includes two weekly one hour individual sessions; Hypnotic (zopiclone) in a dose of 7,5 mg has to be taken 30 minutes before bedtime for two weeks

Measures Questionnaires. During the first visit patients underwent structured clinical interview and filled in self-report questionnaires: Beck Depression Inventory (BDI), State-trait anxiety inventory (STAI), Toronto Alexithymia Scale - short version (TAS-20) , Big Five Questionnaire (BFQ-2R), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Dysfunctional beliefs about sleep scale (DBAS), Sleep hygiene index (SHI).

During the next 4 visits participants repeatedly underwent diagnostic tests included BDI, STAI, PSQI, ISI, DBAS, SHI.

Participants kept daily sleep diaries where they recorded bedtime and morning rise time, sleep onset latency (SOL), number of night awakenings and time of wakefulness after sleep onset before waking up (WASO) for the whole study period.

On the last visit participants completed questionnaire for assessment of effectiveness of treatment along with diagnostic routine. Patients were asked to rank the effectiveness of proposed methods of treatment (didactic presentation, stimulus control, sleep restriction, relaxing recording and zopiclone) in ascending order from 1 to 5 points (5 seems most effective).

Polysomnography. Participants underwent in-lab PSG (1 night without adaptation night) prior to the treatment in order to exclude other disorders producing subjective sleep complaints (sleep apnea, periodic limb movements disorder). Standard polysomnography montage including 6 monopolar electroencephalography (EEG) channels; 1 submental electromyogram (EMG) channel; 2 electrooculogram (EOG) channels; 2 EMG channels of the right and left tibialis anterior muscles; 1 electrocardiogram channel; oronasal airflow pressure; thoracic and abdominal efforts; respiratory sound; oxygen saturation; body position with videomonitoring was performed. The objective sleep measures included total sleep time (TST), sleep-onset latency, wake time after sleep onset (WASO), number of awakenings, sleep efficiency (the ratio of TST to time spent in bed multiplied on 100%, SE), percentage of sleep stages. PSG data were analysed according the 2007 American Academy of Sleep Medicine criteria including its revision in 2012.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

Study design implied that every patient underwent two different treatment courses in random sequence: hypnotic or structured educational program (BBT-I) delivered in two sessions.

Subjects were randomly assigned to one of treatment sequences by card sorting method. Patients of the zopiclone-first group underwent the medication therapy for the first two weeks followed by educational program. Patients of the BBT-I-first group received two-week educational program followed by medication therapy.

Each treatment course was separated by 2-weeks washout period that provided the opportunity to evaluate the sustainability of treatment effect.

Before and after each treatment course and after each washout period subjects completed set of questionnaires.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Insomnia Chronic

Intervention

• Behavioral: 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.
  Other Name: BBT-I
• Drug: Zopiclone
  zopiclone intake in a dose of 7,5 mg 30 minutes before bedtime for two weeks
  Other Name: hypnotic

Study Arms

• Experimental: zopiclone first group
  underwent the medication therapy (zopiclone) for the first two weeks followed by brief behavioral therapy
  Interventions:

  • Behavioral: Brief behavioral therapy
  • Drug: Zopiclone
• Experimental: BBT-I first group
  received two-week brief behavioral therapy followed by medication therapy (zopiclone).
  Interventions:

  • Behavioral: Brief behavioral therapy
  • Drug: Zopiclone

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2017): 42
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: March 14, 2017
• Actual Primary Completion Date: March 14, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

meeting the criteria for chronic insomnia according ICSD-3 willingness to take part in the study and signed informed consent form

Exclusion Criteria:

1. unability to stop taking medications that have a proven impact on sleep at least one week before and during the study;
2. history of alcohol or drug abuse;
3. major depressive disorder or other severe mental disorder identified by a clinical assessment and medical history;
4. dementia;
5. pregnancy or lactation;
6. shift or night work;
7. medical problems that would be a direct cause of sleep complaints: moderate/severe sleep apnea, defined as an apnea-hypopnea index of ≥15 events per hour, periodic limb movement disorder defined as a periodic leg movement index ≥15 events per hour or restless legs syndrome;
8. other serious chronic conditions or exacerbation of chronic disorder preventing further participation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03339583
• Other Study ID Numbers: 1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Since our lab has no plans to continue or extend the registered study we are not planning share individual patient data with other researches

• Current Responsible Party: Polina Pchelina, I.M. Sechenov First Moscow State Medical University
• Original Responsible Party: Same as current
• Current Study Sponsor: I.M. Sechenov First Moscow State Medical University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Polina Pchelina, PG student; I.M. Sechenov First Moscow State Medical University

• PRS Account: I.M. Sechenov First Moscow State Medical University
• Verification Date: September 2019