Effects of Epicatechin on Statins for Mitochondrial Dysfunction and Impaired Exercise Capacity

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to gain insight into the side-effects of statin consumption, and assess the ability of epicatechin (a compound in dark chocolate) to counteract or reverse these changes. The investigators' prior research has shown that epicatechin can improve skeletal muscle structure and mitochondrial (which gives us energy) structure.

Detailed Description
-----------------
Patient Inclusion Criteria: Must be between 30-75 years of age. Must have a VO2max greater than 18 ml/kg/min(non-sedentary individuals). Subjects with LDL>100mg/dL (or on drug treatment) Subjects without a prior cerebrovascular event (example: stroke) Subjects without a prior cardiovascular event (example: heart attack) Patient Exclusion Criteria: Liver, thyroid, or kidney disease. Currently taking drugs that interfere with statin metabolism (calcium channel blockers, colchicine etc.). Acute or chronic infectious disease; autoimmune/inflammatory disease, cancer, COPD, anemia, diabetes, psychiatric illness. Non-smokers, prior smokers, or illicit drug users with abstinence >1 year. Subjects taking blood thinners (Coumadin, xarelto, pradaxa, Plavix, effient, apixiban, etc) will be excluded. If subjects are taking aspirin for routine prevention they will be asked to hold aspirin for 7 days prior to biopsy. Routine prevention means that the patients are taking aspirin to reduce their risks, but do not have established cardiovascular disease. History of previous knee surgery and active history of knee pain or neuromuscular disease are exclusions as they are known to affect muscle structure and function. The study will be a double blind placebo controlled study where subjects will be randomized to either of two groups: Simvastatin 40 mg + placebo once daily (statin only group) for 3 months Simvastatin 40 mg + Epi 50 mg once daily (statin + Epi group) for 3 months

Official Title
-----------------
Effects of Epicatechin on Patients With Statin-induced Mitochondrial Dysfunction and Impaired Exercise Capacity

Conditions
-----------------
Statin Intolerance

Intervention / Treatment
-----------------
* Dietary Supplement: Pure epicatechin capsules (50mg)
* Drug: Simvastatin (40mg)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Patient Inclusion Criteria: Must be between 30-75 years of age LDL>100mg/dL (or on drug treatment) VO2 max greater than 25 ml/kg/min Patient Exclusion Criteria: Liver or kidney disease Currently taking drugs that interfere with statin metabolism Currently taking blood thinners Acute or chronic infectious disease; autoimmune/inflammatory disease, cancer, COPD, anemia, psychiatric illness, insulin-dependent diabetes smokers or illicit drug users adverse cardiovascular event (ex: heart attack) history of knee surgery or active history of knee pain

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Statin only<br>The subject will consume simvastatin (40mg) and placebo once daily for 3 months. | Drug: Simvastatin (40mg)<br>* A cholesterol-lowering medication that blocks the production of cholesterol.<br>Other: Placebo<br>* A substance that has no therapeutic effect and will act as a control.<br>|
| Experimental: Statin and epicatechin<br>The subject will consume simvastatin (40mg) and pure epicatechin capsules (50mg) once daily for 3 months. | Dietary Supplement: Pure epicatechin capsules (50mg)<br>* Epicatechin is a compound found naturally in dark chocolate.<br>Drug: Simvastatin (40mg)<br>* A cholesterol-lowering medication that blocks the production of cholesterol.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Functional Capacity | Cardiopulmonary exercise protocol will be used to measure VO2max to assess functional capacity. | Baseline and 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
myopathy, muscular weakness, cramping, fatigue