Dose-response Study of Carduus Marianus in Centesimal Scale for Dyslipidemia in Climacteric Overweighed or Obese Women.

Study Overview
=================
Brief Summary
-----------------
Metabolic disorders including hypercholesterolemia and hypertriglyceridemia are present in climacteric women. Carduus marianus is a homeopathic medicine that traditionally has been used for hepatic diseases. It has been used for reducing hypercholesterolemia and hypertriglyceridemia also. The aim of this study is to investigate the most effective dose of Carduus marianus in centesimal scale (6cH, 12cH, 30cH, placebo) plus diet and exercise for reducing hypertriglyceridemia and/or hypercholesterolemia in climacteric women.

Detailed Description
-----------------
The prevalence of metabolic disorders including dyslipidemia increases as women transition from premenopause to postmenopause. This increases the risk for morbidity and mortality from cardiovascular diseases. Carduus marianus is a homeopathic medicine that traditionally has been used for hepatic diseases. Silymarin, isolated from Carduus marianus, owe its therapeutic and hepatoprotective effects to its strong antioxidant and anti-inflammatory properties. Carduus marianus is frequently used in clinical practice and reduces plasma level of triglycerides, total cholesterol and LDL in humans with dyslipidemia. Not all homeopaths agree on dosage and potency when prescribing homeopathic medicines. The aim of this study is to assess: (1) the most effective dose of Carduus marianus in centesimal scale for reducing hypertriglyceridemia and/or hypercholesterolemia in climacteric women; (2) the effect of Carduus marianus in other metabolic parameters (glucose, glycosylated hemoglobin, insulin resistance, weight, body mass index, waist circumference). This is a 8-week, double-blind, randomized, parallel, four-group, dose-response study to assess the safety and efficacy of Carduus marianus in 6cH, 12cH, 30cH and placebo plus diet and exercise, for reducing hypertriglyceridemia and/or hypercholesterolemia in climacteric women.

Official Title
-----------------
Dose-response Study of the Efficacy and Safety of Carduus Marianus in Centesimal Scale for Dyslipidemia in Overweighed or Obese Women in Peri- and Postmenopause: a Randomized Controlled Trial

Conditions
-----------------
Dyslipidemia, Menopause, Obesity

Intervention / Treatment
-----------------
* Drug: Carduus marianus 6cH
* Drug: Carduus marianus 12cH
* Drug: Carduus marianus 30cH
* Drug: Placebo
* Behavioral: Exercise
* Other: Diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: women 40-65 years in early or late transition to menopause or postmenopause according to STRAW classification hypertriglyceridemia [>150 <1000 mg/dL], and/or hypercholesterolemia [>200mg/dL] overweight or obesity [BMI >25 Kg/m2] fasting glucose <126mg/dL glycosylated hemoglobin <6.5% be willing and capable to follow study procedures. Exclusion Criteria: history of cardiovascular disease or coronary risk equivalents secondary hyperlipidemia caused by diabetes mellitus, renal, liver or thyroid diseases hypolipidemic agents, antidiabetic medication, hormone replacement therapy, tamoxifen, raloxifene, danazol, isotretinoin, acitretin, cyclosporin, azathioprine, protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir, saquinavir), antipsychotics (clozapine), seizure medication (carbamazepine, valproic acid, phenobarbital, phenytoin) either on-going or any time in the previous 2 months any other clinically significant illness that, in the opinion of the investigator, might put the patient at risk of harm during the study or might adversely affect the interpretation of the study data pregnancy or breastfeeding.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 65 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diet + exercise + Carduus marianus 6cH<br>Diet (1600 cal/day) + aerobic exercise (30 min daily) + Carduus marianus 6cH, 24 drops diluted in 20 ml of water, by mouth, every 8 hours for 8 weeks. | Drug: Carduus marianus 6cH<br> <br> Behavioral: Exercise<br>* aerobic exercise, 30 minutes, daily<br>Other: Diet<br>* 1600 calories<br>|
| Experimental: Diet + exercise + Carduus marianus 12cH<br>Diet (1600 cal/day) + aerobic exercise (30 min daily) + Carduus marianus 12cH, 24 drops diluted in 20 ml of water, by mouth, every 8 hours for 8 weeks. | Drug: Carduus marianus 12cH<br> <br> Behavioral: Exercise<br>* aerobic exercise, 30 minutes, daily<br>Other: Diet<br>* 1600 calories<br>|
| Experimental: Diet + exercise + Carduus marianus 30cH<br>Diet (1600 cal/day) + aerobic exercise (30 min daily) + Carduus marianus 30c, 24 drops diluted in 20 ml of water, by mouth, every 8 hours for 8 weeks. | Drug: Carduus marianus 30cH<br> <br> Behavioral: Exercise<br>* aerobic exercise, 30 minutes, daily<br>Other: Diet<br>* 1600 calories<br>|
| Placebo Comparator: Diet + exercise + placebo<br>Diet (1600 cal/day) + aerobic exercise (30 min daily) + placebo (87°alcohol), 24 drops diluted in 20 ml of water, by mouth, every 8 hours for 8 weeks. | Drug: Placebo<br> <br> Behavioral: Exercise<br>* aerobic exercise, 30 minutes, daily<br>Other: Diet<br>* 1600 calories<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline level of triglycerides at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline level of total cholesterol at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline level of LDL cholesterol at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline level of HDL cholesterol at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline level of fasting glucose at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline level of glycosylated hemoglobin at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline [HOMA-IR=insulin(mU/ml) X glucose (mg/dl)/405] at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline weight (kg) at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline body mass index (Kg/m2) at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Change from baseline waist circumference (cm) at 4 and 8 weeks. |  | 4 and 8 weeks after randomization | 
| Adverse events | Untoward medical occurrence associated with the use of a drugs in humans, whether or not considered drug related. | 4 weeks after randomization | 
| Adverse events | Untoward medical occurrence associated with the use of a drugs in humans, whether or not considered drug related. | 8 weeks after randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Obesity, Homeopathy, Carduus marianus, Dyslipidemia, Climacteric, Triglycerides, Cholesterol, Insulin resistance, LDL-cholesterol, HDL-cholesterol