Flaxseed in Treating Postmenopausal Women With Hot Flashes Who Have a History of Breast Cancer or Other Cancer or Who Do Not Wish to Take Estrogen Therapy

• ClinicalTrials.gov Identifier: NCT00956813
• Recruitment Status: Completed
• First Posted: August 11, 2009
• Results First Posted: April 4, 2017
• Last Update Posted: April 4, 2017
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Supportive Care
• Conditions: Breast Cancer; Hot Flashes; Menopausal Symptoms; Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Dietary Supplement: flaxseed; Other: placebo
• Enrollment: 210

Participant Flow

Recruitment Details
Pre-assignment Details	One-hundred-five patients were randomized to each of the Flaxseed arm and the Placebo arm. After unblinding, all patients had the option of continuing Flaxseed treatment for 6 additional weeks to obtain longer term information about the effects of flaxseed for the management of hot flashes and to allow the placebo arm to try the flaxseed.

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Period Title: Flaxseed and Placebo
Started	105	105
Completed	97	100
Not Completed	8	5
Reason Not Completed
Withdrawal by Subject	5	4
Ineligible	3	1
Period Title: Continuation Phase
Started	80	0
Completed	80	0
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Flaxseed	Placebo	Total
Arm/Group Description		Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.	Total of all reporting groups
Overall Number of Baseline Participants		105	105	210
Baseline Analysis Population Description		All patients that registered are included in baseline characteristics for the Flaxseed and Placebo Period. Patients who continued treatment during the Optional Continuation Period were a subset of the original 210 patients and are reported separately.
Age, Customized [1]; Measure Type: Count of Participants; Unit of measure: Participants
Flaxseed and Placebo Period	Number Analyzed	105 participants	105 participants	210 participants
	<50	25 23.8%	24 22.9%	49 23.3%
	>=50	80 76.2%	81 77.1%	161 76.7%
Optional Flaxseed Continuation	Number Analyzed	80 participants	0 participants	80 participants
	<50	25 31.3%		25 31.3%
	>=50	55 68.8%		55 68.8%
		[1] Measure Analysis Population Description: Patients that continued with the Optional Flaxseed Continuation Period were combined for baseline analysis.
Sex: Female, Male [1]; Measure Type: Count of Participants; Unit of measure: Participants
Flaxseed and Placebo Period	Number Analyzed	105 participants	105 participants	210 participants
	Female	105 100.0%	105 100.0%	210 100.0%
	Male	0 0.0%	0 0.0%	0 0.0%
Optional Flaxseed Continuation	Number Analyzed	80 participants	0 participants	80 participants
	Female	80 100.0%	0	80 100.0%
	Male	0 0.0%	0	0 0.0%
		[1] Measure Analysis Population Description: Patients that continued with the Optional Flaxseed Continuation Period were combined for baseline analysis.
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	105 participants	105 participants	210 participants
		105	105	210

Outcome Measures

1. Primary Outcome

Title	To Evaluate the Efficacy of Flaxseed on Hot Flash Scores in Women as Measured by a Daily Prospective Hot Flash Diary.
Description	The intra-patient difference in hot flash activity between baseline (study week 1) and treatment termination (study week 7) is the primary endpoint. The hot flash activity will be measured by the weekly average hot flash score which is a composite entity of both frequency and severity of hot flashes. The hot flash severities are graded from 1 to 4, ranging from mild, to moderate, to severe to very severe. The daily hot flash score is computed by multiplying the mean grade of severity by the frequency during every 24 hour period. Therefore, a score of zero is the lowest possible score and can be interpreted as having no hot flashes. The average daily hot flash score during the baseline week was compared to the average daily value during week 7. The primary method of analysis will be the independent sample t-test to examine the change of weekly average hot flash score from baseline to treatment termination between flaxseed and placebo arms.
Time Frame	Baseline and 7 weeks

Outcome Measure Data

Analysis Population Description

Per protocol, the study was powered for 77 patients on each arm. With 20% over-accrual, the analysis began after 94 patients registered to each arm. 25 patients from Flaxseed were not used (4 cancel, 2 ineligible, 12 refused further treatment, 5 due to adverse events, 2 noncompliance). 17 from the placebo arm were not used (3,1,5,7,1 respective)

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description:	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Overall Number of Participants Analyzed	69	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	-4.9 (6.41)	-3.5 (6.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.29
	Comments	[Not Specified]
	Method	t-test, 2 sided
	Comments	[Not Specified]

2. Secondary Outcome

Title	Toxicity as Measured by CTCAE v3.0
Description	Frequency and severity of adverse events were reported by patients weekly evaluated through clinical assessment by NCI CTCAE v3.0. The number of patients reporting grade 3 or higher events are reported in this outcome measure. For a full list of all events, please refer to the Adverse Events section of this report.
Time Frame	Up to 7 weeks

Outcome Measure Data

Analysis Population Description

All patients treated during the Double-blinded period of the study were included in this analysis

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description:	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Overall Number of Participants Analyzed	101	102
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 3+ Adverse Event	0 0.0%	1 1.0%
Grade 4+ Adverse Event	0 0.0%	0 0.0%

3. Secondary Outcome

Title	Change of Mood as Measured by the Profile of Mood States (POMS)
Description	Profile of Mood States (POMS) was used to look at total mood disturbance as well as the subscales of tension-anxiety, fatigue-inertia, and vigor-activity. The POMS is a well known, well validated, reliable measure of psychological distress which includes 6 subscales of fatigue-inertia, vigor-activity, tension-anxiety, depression-dejection, anger-hostility, and confusion-bewilderment. The entire scale can be scored to provide a measure of total mood disturbance. The measure contains adjectives related to mood which are scored from 0 (not at all) to 4 (extremely). Individual scores were converted to a 0-100 scale where 100 is best quality of life. The change of mood as measured by the POMS from baseline to treatment termination between flaxseed versus placebo arms was compared using Kruskal-Wallis test. The mean change in total score for each arm is reported.
Time Frame	Baseline and up to 7 weeks

Outcome Measure Data

Analysis Population Description

Per protocol, the study was powered for 77 patients on each arm. With 20% over-accrual, the analysis began after 94 patients registered to each arm. 25 patients from Flaxseed were not used (4 cancel, 2 ineligible, 12 refused further treatment, 5 due to adverse events, 2 noncompliance). 17 from the placebo arm were not used (3,1,5,7,1 respective)

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description:	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Overall Number of Participants Analyzed	69	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	6.6 (9.92)	5.7 (9.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.93
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

4. Secondary Outcome

Title	Change of Menopause Specific Quality of Life as Measured by the Menopause Specific Quality of Life (MENQOL)
Description	The change in quality of life as measured by the MENQOL from baseline to treatment termination between flaxseed versus placebo arms was evaluated. On a 0-6 scale, patients were asked to answer questions in in each of 4 domain scores (Vasomotor, Psychosocial, Physical, Sexual) Scores were converted to a 0-100 scale where 100 is best QOL. The change in score from baseline to end of treatment were analyzed separately for each domain. Here we report the mean change in score for each category.
Time Frame	Baseline and up to 7 weeks

Outcome Measure Data

Analysis Population Description

Per protocol, the study was powered for 77 patients on each arm. With 20% over-accrual, the analysis began after 94 patients registered to each arm. 25 patients from Flaxseed were not used (4 cancel, 2 ineligible, 12 refused further treatment, 5 due to adverse events, 2 noncompliance). 17 from the placebo arm were not used (3,1,5,7,1 respective)

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description:	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Overall Number of Participants Analyzed	69	77
Mean (Standard Deviation); Unit of Measure: units on a scale
Change in Vasomotor score	22.5 (20.13)	18.7 (22.04)
Change in Psychosocial score	9.9 (12.49)	11.1 (15.02)
Change in Physical Score	9.3 (13.44)	11.8 (15.19)
Change in Sexual Score	14.4 (18.27)	14.4 (22.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	Testing the change in score from baseline to treatment completion for vasomotor-related questions in the MENQOL form.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.19
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	Testing the change in score from baseline to treatment completion for Psychosocial-related questions in the MENQOL form.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.78
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	Testing the change in score from baseline to treatment completion for Physical-related questions in the MENQOL form.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.238
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	Testing the change in score from baseline to treatment completion for Sexually-related questions in the MENQOL form.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.497
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

5. Secondary Outcome

Title	Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS)
Description	The change of daily interference as measured by the HFRDIS from baseline to treatment termination between flaxseed versus placebo arms was evaluated with an independent t-test for continuous data. On a 0-10 scale, patients were asked to describe how hot flashes interfered with 10 different aspects of their life (work, social activities, leisure activities, sleep, mood, concentration, relationships with others, sexuality, enjoyment of life and overall quality of life). Scores were converted to a 0-100 scale where 100 is best QOL.The HFRDIS total score was the average of the 10 individual questions. The change in total score from baseline to end of treatment was analyzed between the groups using a Kruskal-Wallace test.
Time Frame	Baseline and up to 7 weeks

Outcome Measure Data

Analysis Population Description

Per protocol, the study was powered for 77 patients on each arm. With 20% over-accrual, the analysis began after 94 patients registered to each arm. 25 patients from Flaxseed were not used (4 cancel, 2 ineligible, 12 refused further treatment, 5 due to adverse events, 2 noncompliance). 17 from the placebo arm were not used (3,1,5,7,1 respective)

Arm/Group Title	Flaxseed	Placebo
Arm/Group Description:	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.	Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.
Overall Number of Participants Analyzed	69	77
Mean (Standard Deviation); Unit of Measure: units on a scale
	13.9 (18.57)	9.8 (19.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Flaxseed, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.089
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

Adverse Events

Time Frame	The Placebo and Flaxseed arm were the double-blinded first 7 weeks of treatment. After the 7 weeks of double-blinded treatment, patients were given the option of continuing treatment according to the Flaxseed arm for up to 6 additional weeks.
Adverse Event Reporting Description	Adverse events were assessed every week during treatment. All patients that began study treatment and were assessed at least once for adverse events were included in this analysis
Arm/Group Title	Flaxseed		Placebo		Optional Continuation Period
Arm/Group Description	Patients receive 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.		Patients Identical looking bar with same calorie and total fat content but without flaxseed or lignans once daily.		After completing the Placebo/Flaxseed double-blind period, patients were allowed to continue with 1 Nutrigrad™ flaxseed bar containing 7.5 grams flaxseed, 410 mg lignans,once daily.
All-Cause Mortality
	Flaxseed		Placebo		Optional Continuation Period
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--		--/--
Serious Adverse Events
	Flaxseed		Placebo		Optional Continuation Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0.00%)		0/102 (0.00%)		0/76 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Flaxseed		Placebo		Optional Continuation Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/101 (60.40%)		71/102 (69.61%)		32/76 (42.11%)
Gastrointestinal disorders
Abdominal distension † 1	33/101 (32.67%)	53	30/102 (29.41%)	50	11/76 (14.47%)	21
Abdominal pain † 1	2/101 (1.98%)	2	2/102 (1.96%)	2	1/76 (1.32%)	1
Constipation † 1	1/101 (0.99%)	2	0/102 (0.00%)	0	0/76 (0.00%)	0
Diarrhea † 1	11/101 (10.89%)	15	16/102 (15.69%)	19	6/76 (7.89%)	7
Flatulence † 1	45/101 (44.55%)	93	45/102 (44.12%)	79	27/76 (35.53%)	55
Nausea † 1	21/101 (20.79%)	29	16/102 (15.69%)	21	5/76 (6.58%)	8
Vomiting † 1	2/101 (1.98%)	3	6/102 (5.88%)	7	3/76 (3.95%)	4
General disorders
Fatigue † 1	0/101 (0.00%)	0	0/102 (0.00%)	0	1/76 (1.32%)	2
Infections and infestations
Sinusitis † 1	1/101 (0.99%)	1	0/102 (0.00%)	0	0/76 (0.00%)	0
Metabolism and nutrition disorders
Anorexia † 1	0/101 (0.00%)	0	0/102 (0.00%)	0	1/76 (1.32%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/101 (0.00%)	0	1/102 (0.98%)	1	0/76 (0.00%)	0
Nervous system disorders
Dizziness † 1	0/101 (0.00%)	0	0/102 (0.00%)	0	1/76 (1.32%)	1
Headache † 1	1/101 (0.99%)	1	0/102 (0.00%)	0	0/76 (0.00%)	0
Skin and subcutaneous tissue disorders
Pruritus † 1	1/101 (0.99%)	1	9/102 (8.82%)	13	2/76 (2.63%)	4
Rash maculo-papular † 1	4/101 (3.96%)	6	7/102 (6.86%)	13	0/76 (0.00%)	0
Vascular disorders
Hematoma † 1	1/101 (0.99%)	1	0/102 (0.00%)	0	0/76 (0.00%)	0
Hot flashes † 1	0/101 (0.00%)	0	1/102 (0.98%)	1	0/76 (0.00%)	0
Vascular disorders - Other, specify † 1	0/101 (0.00%)	0	1/102 (0.98%)	3	0/76 (0.00%)	0
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 12

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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: Debra L. Barton, RN, PhD, AOCN
• Organization: Mayo Clinic
• EMail: barton.debra@mayo.edu

Publications of Results:

Pruthi S, Qin R, Terstreip SA, Liu H, Loprinzi CL, Shah TR, Tucker KF, Dakhil SR, Bury MJ, Carolla RL, Steen PD, Vuky J, Barton DL. A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for the treatment of hot flashes: North Central Cancer Treatment Group N08C7. Menopause. 2012 Jan;19(1):48-53. doi: 10.1097/gme.0b013e318223b021.

Pruthi S, Qin R, Terstriep SA, et al.: The evaluation of flaxseed for hot flashes: results of a randomized, controlled trial, NCCTG study N08C7. [Abstract] J Clin Oncol 29 (Suppl 15): A-CRA9015, 2011.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00956813
• Other Study ID Numbers: N08C7; NCCTG-N08C7; CDR0000644811 ( Registry Identifier: PDQ (Physician Data Query) ); NCI-2011-01928 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
• First Submitted: August 8, 2009
• First Posted: August 11, 2009
• Results First Submitted: November 29, 2016
• Results First Posted: April 4, 2017
• Last Update Posted: April 4, 2017