Phase III, Randomized, Placebo-controlled, Double-Blind Trial of Flaxseed for the Treatment of Hot Flashes
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 210
- Locations
- 107
- Primary Endpoint
- To Evaluate the Efficacy of Flaxseed on Hot Flash Scores in Women as Measured by a Daily Prospective Hot Flash Diary.
Study Overview
Brief Summary
RATIONALE: Estrogen can relieve the symptoms of menopause, but can also cause the growth of breast cancer cells. Flaxseed may reduce the number of hot flashes and improve mood and quality of life in postmenopausal women not receiving estrogen therapy.
PURPOSE: This randomized phase III trial is studying flaxseed to see how well it works 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.
Detailed Description
OBJECTIVES:
- To evaluate the efficacy of flaxseed on hot flash scores in women with a history of breast cancer or other cancer or in women who do not wish to take estrogen therapy for fear of increased risk of breast cancer as measured by a daily prospective hot flash diary.
- To evaluate the side effect profile of flaxseed in this population.
- To evaluate the effects of flaxseed on mood (per the Profile of Mood States) and broader menopausal symptoms (per the MENQOL), daily interference from hot flashes (per the HFRDIS), and perception of benefit (per Global Impression of Change).
OUTLINE: Patients are stratified according to age (18-49 years vs ≥ 50 years); treatment with tamoxifen citrate, selective estrogen receptor modulators, or aromatase inhibitors (yes vs no); duration of hot flashes (≤ 9 months vs > 9 months); and daily frequency of hot flashes (4-9 vs ≥ 10). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral flaxseed in the form of a bar similar to a granola bar once daily.
- Arm II: Patients receive oral placebo bar once daily. In both arms, treatment continues for 6-12 weeks. Patients in arm II may crossover to receive treatment as in arm I after 6 weeks.
Patients complete questionnaires (Hot Flash Diary, Side Effect Experience Questionnaire, Profile of Mood States, Hot Flash Related Daily Interference Scale, and Menopause Specific Quality of Life) at baseline and periodically during treatment. Patients are contacted by telephone at the end of weeks 2, 4, 5, and 7 to assess product tolerability, document compliance, encourage completion of questionnaires, and address problems.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Bothersome hot flashes, defined by their occurrence ≥ 28 times per week and of sufficient severity to make the patient desire therapeutic intervention
- •Presence of hot flashes for ≥ 1 month
- •Meets 1 of the following criteria:
- •History of breast cancer or other cancer (currently without malignant disease)
- •No history of breast cancer and wishes to avoid estrogen due to a perceived increased risk of breast cancer
- •Hormone receptor status not specified
- •Postmenopausal as defined by 1 of the following*:
- •NOTE: *Women with ≥ 1 ovary but without a uterus should be deemed postmenopausal by either age > 55 OR a combination of estrogen within a postmenopausal range (per local lab) and follicle-stimulating hormone > 40 mIU/mL
- •Absence of a period in the past 12 months
- •Bilateral oophorectomy
- •ECOG performance status 0-1
- •Life expectancy ≥ 6 months
- •Able to complete questionnaire(s) alone or with assistance
- •No diabetes requiring oral or injectable antihyperglycemics
- •No hypotension
- •No history of allergic or other adverse reaction to flaxseed
- •No irritable bowel syndrome, colitis, Crohn disease, or any gastrointestinal condition where the patient should not consume and/or has an intolerance/allergies to seeds or nuts
- •At least 4 weeks since prior and no concurrent or planned androgens, estrogens, or progestational agents
- •Tamoxifen, raloxifene, or aromatase inhibitors are allowed provided the patient has been on a constant dose for ≥ 4 weeks and is not expected to stop the medication during study treatment
- •At least 4 weeks since prior and no concurrent anti-cancer therapies of any kind
- •Trastuzumab allowed
- •No concurrent treatment with other anti-cancer therapies of any kind except for trastuzumab or endocrine therapies
- •No concurrent (≤ 7 days prior to registration) or planned use of other agents for treating hot flashes (i.e., gabapentin, clonidine, antidepressants, estrogen treatment, megestrol acetate, or Bellergal)
- •Stable dose of vitamin E (as a general vitamin supplement) allowed provided it is ≤ 800 IU/day, it was started > 30 days before study initiation, and is to be continued through study period
- •Patients who have been using antidepressants for mood and have been on a stable dose for over a month and meet the eligibility criteria for hot flash frequency and duration are eligible
- •No concurrent anticoagulants or anti-platelets (1 mg of Coumadin for central line patency allowed)
- •Aspirin allowed (≤ 81 mg)
- •No concurrent anti-hypertensives
- •No other concurrent herbal supplements for any reason, including soy and soy supplements (i.e., powders, pills, or milk)
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I
Patients receive oral flaxseed in the form of a bar similar to a granola bar once daily.
Intervention: flaxseed (Dietary Supplement)
Arm II
Patients receive oral placebo bar once daily.
Intervention: placebo (Other)
Outcomes
Primary Outcomes
To Evaluate the Efficacy of Flaxseed on Hot Flash Scores in Women as Measured by a Daily Prospective Hot Flash Diary.
Time Frame: Baseline and 7 weeks
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.
Secondary Outcomes
- Toxicity as Measured by CTCAE v3.0(Up to 7 weeks)
- Change of Mood as Measured by the Profile of Mood States (POMS)(Baseline and up to 7 weeks)
- Change of Daily Interference as Measured by the Hot Flash Related Daily Interference Scale (HFRDIS)(Baseline and up to 7 weeks)
- Change of Menopause Specific Quality of Life as Measured by the Menopause Specific Quality of Life (MENQOL)(Baseline and up to 7 weeks)