Effect of Menopause Relief EP-40 in Women With Menopausal Symptoms

Study Overview
=================
Brief Summary
-----------------
This study compares the efficacy of a fixed combination of black cohosh (EP-40) and Rhodiola rosea (EPR-7) with low (6.5 mg) and high doses (500 mg) of a standardized black cohosh extract only in adult woman with menopausal complaints.

Detailed Description
-----------------
Due to the problems caused by Hormone Replacement Therapy with chemical entities, some medicinal plants used in the traditional systems of medicine have shown immense potential in non-hormonal treatment of menopausal symptoms without major adverse events. We hypothesize that Menopause Relief EP-40 (a fixed combination of Cimicifuga EP-40 and Rhodiola EPR-7 extracts) will significantly relieve menopausal complaints such as hot flushes, profuse sweating hot flushes, excessive perspiration, night sweats, sleep disorders, nervousness, mood swings, physical and mental fatigue as compared to EP-40® capsules or placebo in adult females in menopause.

Official Title
-----------------
Efficacy of Menopause Relief EP-40 - Fixed Combination of Cimicifuga EP-40 and Rhodiola EPR-7 Extracts in Women With Menopausal Symptoms: A Randomized, Double Blind, Placebo Controlled Study

Conditions
-----------------
Menopause

Intervention / Treatment
-----------------
* Dietary Supplement: Menopause Relief EP-40
* Dietary Supplement: Low Dose Black Cohosh
* Dietary Supplement: High Dose Black Cohosh
* Dietary Supplement: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of menopausal female climacteric states (N95.1 according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision, ICD-10, Version for 2014) which is characterized by symptoms such as flushing, sleeplessness, headache, lack of concentration associated with menopause, etc Patients suffering from menopausal syndrome with neurovegetative components which have been stable anamnestically during the last 2 weeks No medication taken for management of menopausal syndrome with neurovegetative components during the last 4 weeks Ability to understand and provide signed informed consent Ability to participate in the study In some cases, diagnosis should be confirmed by blood tests of follicle-stimulating hormone (≥ 40 IU/L) [postmenopausal status], thyroid function with normal serum free T4 (fT4), estrogen (estrodiol levels) [premenopausal 30-400 pg/mL; after menopause <30 pg/mL] Exclusion Criteria: subjects with previous or current psychological disease that could interfere with their ability to participate in the study anamnestic or current alcohol or drug abuse concomitant treatment with psychotropic (in particular benzodiazepines, antidepressants, hypnotics or neuroleptics, tamoxifen, clomiphene, and danazol) or hormonally acting drugs such as hormone replacement therapy (HRT) hyperthyroidism malignant tumors continuous climacteric bleeding and complaints related to myomas patients who have taken another experimental drug within a 4-week period prior to the trial pregnancy/lactation serious internal disease previous organ transplantation premenopausal women with insufficient contraceptive protection hypersensitivity to one of the ingredients of the trial medication a body mass index of >30

Ages Eligible for Study
-----------------
Minimum Age: 41 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: Menopause Relief EP-40<br>Fixed combination of black cohosh EP-40 and Rhodiola rosea EPR-7 206.5 mg orally twice daily; daily dose 413 mg of active ingredients | Dietary Supplement: Menopause Relief EP-40<br>* Fixed combination of black cohosh and Rhodiola rosea<br>|
| Active Comparator: High Dose Black Cohosh<br>Black cohosh 500 mg orally twice daily; daily dose 1000 mg of active ingredient | Dietary Supplement: High Dose Black Cohosh<br>* 500 mg black cohosh<br>|
| Placebo Comparator: Placebo<br>Placebo capsule 600 mg excipients orally twice daily | Dietary Supplement: Placebo<br>* 600 mg excipient<br>|
| Active Comparator: Low Dose Black Cohosh<br>Black cohosh 6.5 mg orally twice daily; daily dose 13 mg of active ingredient | Dietary Supplement: Low Dose Black Cohosh<br>* 6.5 mg black cohosh<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kupperman Menopausal Index (KMI) | A modified total Kupperman Index (KMI) score and its sub-items will be used. It is a 10-item questionnaire of single symptoms with scores ranging from 0 to 3 (none, mild, moderate and severe). Total KMI is defined as the sum of sub-item scores multiplied by any weighting factors. The maximum value of the total KMI is 48. The primary outcome will be the difference in the changes from baseline to the end of therapy (week 12), between verum groups and placebo, assessed by the total KMI and stratified by individual baseline scores in an intention-to-treat (ITT) analysis (patients treated with study medication and with at least one efficacy assessment after baseline). | 12 weeks | 
| Menopause Rating Scale (MRS) | The MRS is a patient reported assessment of 11 symptoms of menopause on a scale of 0 (none) to 4 (very severe). The MRS groups symptoms into three subscales: psychological, somatic, and urogenital. A composite score is calculated by adding the items in each dimension (subscale). The total score is the sum of the three dimensional scores. The primary outcome will be the difference in the changes from baseline to the end of therapy (week 12), between both verum groups and placebo, assessed by the MRS and stratified by individual baseline scores in an intention-to-treat (ITT) analysis (patients treated with study medication and with at least one efficacy assessment after baseline). | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cimicifuga, Rhodiola, Menopause Symptoms