Clinical Evaluation of Effectiveness and Safety of Amberen and Smart B in Perimenopausal Women.

Study Overview
=================
Brief Summary
-----------------
To evaluate effectiveness and safety of combined use of dietary supplements Amberen and Smart B in women with a typical (without complications) form of climacteric syndrome, with mild to moderate symptoms in perimenopause.

Detailed Description
-----------------
To evaluate effectiveness of combined use of dietary supplements Amberen and Smart B in women vasomotor, psychosomatic, psychological and other climacteric symptoms in perimenopause. To evaluate safety of combined use of dietary supplements Amberen and Smart B in women with vasomotor, psychosomatic, psychological and other climacteric symptoms in perimenopause. To develop recommendations for combined use of dietary supplements Amberen and Smart B for women with vasomotor, psychosomatic, psychological and other climacteric symptoms in perimenopause.

Official Title
-----------------
Clinical Evaluation of Effectiveness and Safety of Combined Use of Dietary Supplements Amberen and Smart B in Women With Climacteric Syndrome in Perimenopause

Conditions
-----------------
Perimenopause, Climacteric Syndrome

Intervention / Treatment
-----------------
* Dietary Supplement: Amberen
* Dietary Supplement: Smart B
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects, 50 years of age or younger; Subjects in the second phase of menopausal transition as per STRAW 10+ i.e. interval of amenorrhea 60 days or more (with regular menstrual cycle during earlier reproductive stages). Subjects with diagnosis of mild to moderate climacteric syndrome; Recent (up to 12 months prior to study enrollment) breast exam results, including mammogram, that rule out malignancies; Recent (up to 3 years prior to study enrollment) cytological screening that rules out vaginal cervix malignancies. Ability to read and understand informed consent form for the study's participation; Ability to adhere to the conditions of the study. Exclusion Criteria: • Postmenopause, including surgical menopause. Presence of hormone-dependent cancers; Presence of other cancers, not in full remission with no recurrence for 5 years or more; Planned hospitalization in the next 6 months; Presence of hormonally-active extragenital endocrine diseases (diabetes; diseases of thyroid, adrenal, pituitary) that require prolonged or life-long therapies Surgical interventions on sex organs or breasts, 1 year or less prior to the screening; Gynecological conditions that may require hormonal therapies or surgeries (uterine myoma, endometriosis, endometrial hyperplasia etc.); Currently undergoing or planning to utilize assisted reproductive technologies; Any abdominal surgeries within less than 3 months prior to the screening; HRT including MHRT or hormonal contraceptives - current or within less than 3 months prior to the screening; Psychiatric conditions; Patients taking any other dietary supplements that can affect climacteric syndrome within the last month before enrolling in the trial; High risk of non-compliance.

Ages Eligible for Study
-----------------
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amberen and Smart B<br>Amberen - a dietary supplement: 2 capsules (one while capsule 200 mg and one orange capsule 200 mg) are taken once a day with a meal, preferably after breakfast, for 3 months. SMART В - a dietary supplement: 1 capsule per day (166 mg) is taken once a day with a meal, preferably after breakfast, for 3 months, concurrently with Amberen. | Dietary Supplement: Amberen<br>* Amberen is a succinate-based dietary supplement previously shown to help provide relief for common menopausal symptoms.<br>Dietary Supplement: Smart B<br>* Smart B contains vitamins B1, B2, B6, B9, B12 and sodium fumarate.<br>|
| Placebo Comparator: Placebo<br>Placebo is taken as follows: 3 capsules (one while capsule 200 mg, one orange capsule 200 mg, one capsule 166mg) are taken once a day with a meal, preferably after breakfast, for 3 months. Placebo capsules are identical to Amberen and Smart B capsules. | Dietary Supplement: Placebo<br>* Placebo capsules are identical to Amberen and Smart B capsules.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart beating quickly and strongly symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 1 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Feeling tense or nervous symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 2 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Difficulty sleeping symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 3 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Increased Excitability symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 4 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Panic attacks symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 5 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Difficulty concentrating symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 6 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Feeling tired or lacking energy symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 7 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Loss of interest in most things symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 8 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Feeling of sadness or depression symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 9 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Crying spells symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 10 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Irritability symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 11 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Feeling dizzy or faint symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 12 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Pressure or tightness in head or body symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 13 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Parts of body feeling numb or tingling symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 14 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Headaches symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 15 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Muscle or joint pains symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 16 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Loss of feeling in hands or feet symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 17 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Breathing difficulties symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 18 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Hot flushes symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 19 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Night sweats symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 20 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 days and 180 days | 
| Loss of interest in sex symptom (Greene Climacteric Scale) | Statistically significant change in designated symptom severity, compared between arms. This is question 21 of the Greene Climacteric Scale; the subjects rank degrees of bother of the symptom as 1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely | 90 and 180 days | 
| Blood plasma estradiol levels, pg/ml | Statistically significant changes in the levels, compared between arms | 90 and 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| State-Trait Anxiety Inventory (State anxiety sub-scale) | Statistically significant change of the score in corresponding sub-scale. Scores range from 20 to 80, with higher scores correlating with greater anxiety. | 90 and 180 days | 
| State-Trait Anxiety Inventory (Trait anxiety sub-scale) | Statistically significant change of the score in corresponding sub-scale. Scores range from 20 to 80, with higher scores correlating with greater anxiety. | 90 and 180 days | 
| State-Trait Anxiety Inventory (Actual anxiety, combination of state and trait sub-scales ) | Statistically significant change of the score in corresponding sub-scale. Scores range from 20 to 80, with higher scores correlating with greater anxiety. | 90 and 180 days | 
| Well-being sub-score (Russian well-being, activity and mood questionnaire) | Statistically significant change in designated symptom severity, compared between arms. The sub-scale score varies from 10 to 70 points, with the higher score corresponding to more positive self-evaluation of well-being. | 90 and 180 days | 
| Activity sub-score (Russian well-being, activity and mood questionnaire) | Statistically significant change in designated symptom severity, compared between arms. The sub-scale score varies from 10 to 70 points, with the higher score corresponding to more positive self-evaluation of one's activity. | 90 and 180 days | 
| Mood sub-score (Russian well-being, activity and mood questionnaire) | Statistically significant change in designated symptom severity, compared between arms. The sub-scale score varies from 10 to 70 points, with the higher score corresponding to more positive self-evaluation of one's mood. | 90 and 180 days | 
| Anxiety sub-score (measured by Hospital Anxiety and Depression Scale) | Statistically significant change in designated symptom severity, compared between arms. The scores range from 0 to 21. 0-7 = Normal 8-10 = Borderline abnormal 11-21 = Abnormal | 90 and 180 days | 
| Depression sub-score (measured by Hospital Anxiety and Depression Scale) | Statistically significant change in designated symptom severity, compared between arms. The scores range from 0 to 21. 0-7 = Normal 8-10 = Borderline abnormal 11-21 = Abnormal | 90 and 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
succinate, B complex vitamins, perimenopause