A Nutritional Supplement on Vasomotor Symptoms in Women

This is a randomized, placebo-controlled, double-blind, parallel study, which will include a screening visit (Visit 1; week -3), a 2-week run-in period for baseline determination and assessment of placebo response (Visit 2; week -2; and Visit 3; week -1), one baseline visit (Visit 4; week 0), and three test visits (Visits 5, 6, and 7; weeks 4, 8, and 12).

At Visit 1 (week -3), after subjects have provided informed consent, medical history will be reviewed, and clinic visit procedures will be performed, including assessments of prior/current medication/supplement use, evaluations of inclusion/exclusion criteria, and a last menses query. Fasting (10-14 h) blood samples will be collected for assessment of FSH and estradiol levels. The Soy Food Frequency Questionnaire will be administered and subjects will be instructed to maintain their habitual diets (with the exception of avoiding soy foods) and physical activity patterns throughout the study period. Additionally, subjects will be dispensed the Insomnia Severity Index Questionnaire (ISIQ) and the VMS Diary to assess insomnia and VMS, respectively.

At Visit 2 (week -2), eligible subjects will be instructed to start the run-in placebo product for two weeks. Subjects will be also instructed to continue daily recording in the VMS Diary. At Visit 3 (week -1), the VMS Diary will be collected/reviewed to assess response to the run-in placebo product. Subjects who continue to meet the inclusion/exclusion criteria will be allowed to continue with the study and will be dispensed a sleep tracking device to wear for sleep/wake pattern evaluation.

At Visit 4 (week 0), eligible subjects will be randomized to one of the study products (Active or Placebo) and instructed to consume with water for 12 weeks. Additionally, the Pittsburg Sleep Quality Index (PSQI), RAND-36 Questionnaire, Profile of Mood States (POMS), Day-to-Day Impact of Vaginal Aging Questionnaire (DIVQ), Chalder Fatigue Scale, and Menopause-Specific Quality of Life (MENQOL) Questionnaire will be administered. The VMS Diary and ISIQ will be collected and reviewed.

At Visits 5 and 6 (weeks 4 and 8), the VMS Diary and ISIQ will be collected/reviewed, and the PSQI and MENQOL will be administered. Subjects will return to the clinic prior to Visit 7 (week 12) to receive the sleep tracking device to wear for sleep/wake pattern evaluation one week (7 d) prior to Visit 7 (week 12).

At Visit 7 (week 12), the VMS Diary and ISIQ will be collected and reviewed. The PSQI, RAND-36, POMS, DIVQ, Chalder Fatigue Scale, and MENQOL will be administered and study product will be collected/reviewed, and compliance will be determined. Additionally, the sleep tracker will be collected, and data will be downloaded for evaluation.

Inclusion criteria

• Subject is a perimenopausal or menopausal female experiencing specific menopausal-related VMS.
• Subject has a BMI of ≥18.5 to ≤38.0 kg/m2 at Visit 1 (week -3).
• At screening visit (Visit 1; week -3), subject reports to have 4 or more moderate to severe hot flushes/night sweats during 24 h prior to the visit. At Visit 3 (week -1), subject has ≥25 moderate to severe hot flushes/night sweats per week for one week between Visit 2 and 3 (weeks -2 and -1). At Visit 4 (week 0), subject has an average ≥28 moderate to severe hot flushes/night sweats per week for 2 weeks before Visit 4 (week 0).
• Subject is willing to maintain habitual diet (with the exception of restricted foods/beverages), physical activity patterns, and body weight during the study period.
• Subject is willing to abstain from using products (other than study product) that contains estrogen, progestin, or progesterone within 30 d prior to Visit 1 (week -3) and throughout the study trial.
• If a smoker, subject is willing to maintain current smoking habits.
• Subject has no health conditions that would prevent her from fulfilling the study requirements as judged by the Clinical Investigator on the basis of medical history and routine laboratory test results.
• Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Clinical Investigator.

Exclusion criteria

• Subject has abnormal laboratory test results of clinical importance at Visit 1 (week -3) at the discretion of the Investigator.
• Subject has a history or presence of clinically important pulmonary (including uncontrolled asthma), cardiac (including, but not limited to, atherosclerotic disease, history of myocardial infarction, peripheral arterial disease, stroke), hepatic, renal, endocrine, hematologic, immunologic (including chronic inflammatory conditions), neurologic (such as Alzheimer's or Parkinson's disease), psychiatric (including depression and/or anxiety disorders) or biliary disorders, that, in the opinion of the Clinical Investigator, could interfere with the interpretation of the study results.
• Subject has a history or presence of any gastrointestinal condition that could potentially interfere with absorption of the study product (e.g., inflammatory bowel syndrome, celiac disease, history of gastric bypass surgery).
• Subject has a history of estrogen-dependent neoplasia, atypical ductual hyperplasia of the breast, or undiagnosed vaginal bleeding.
• Subject has a history of endometrial hyperplasia, melanoma, or uterine/endometrial breast or ovarian cancer.
• Subject has uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) as defined by the blood pressure measured at Visit 1 (week -3). One re-test will be allowed on a separate day for subjects whose blood pressure exceeds either of these cut points at Visit 1, in the judgment of the Clinical Investigator.
• Subject has a history of any major trauma or major surgical event within two months of Visit 1 (week -3).
• Subject has a history or presence of cancer in the prior 2 years to Visit 1 (week -3), except for non-melanoma skin cancer.
• Subject has a contraindication to estrogen and/or progestin therapy or allergy/sensitivity to the use of estradiol and/or progesterone, soy, or any components in the study product.
• Subject has used estrogen alone or estrogen/progestin, selective estrogen receptor modulator, testosterone, or estrogen/testosterone within 30 d prior to Visit 1 (week -3).
• Subject has used any prescription or over-the-counter products/supplements (e.g., soy products, herbal supplements) that have potential to alter progesterone or estrogen activity or is being used to treat VMS within 30 d prior to Visit 1 (week -3).
• Subject has self-described extreme or irregular dietary habits, in the opinion of the Clinical Investigator or has been diagnosed with an eating disorder.
• Subject has elective hospitalizations planned (e.g., elective cosmetic procedures) during the study period.
• Subject has been exposed to any non-registered drug product or has participated in another intervention study within 30 d prior to Visit 1 (week -3).
• Subject has a recent history of (within 12 months of screening; Visit 1; week -3) or strong potential for alcohol or substance abuse. Alcohol abuse is defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits).
• Individual has a condition the Clinical Investigator believes would interfere with his ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results, or put the subject at undue risk.