Statin Intolerance
Conditions
Keywords
myopathy, muscular weakness, cramping, fatigue
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: 1. Must be between 30-75 years of age. 2. Must have a VO2max greater than 18 ml/kg/min(non-sedentary individuals). 3. Subjects with LDL\>100mg/dL (or on drug treatment) 4. Subjects without a prior cerebrovascular event (example: stroke) 5. Subjects without a prior cardiovascular event (example: heart attack) Patient Exclusion Criteria: 1. Liver, thyroid, or kidney disease. 2. Currently taking drugs that interfere with statin metabolism (calcium channel blockers, colchicine etc.). 3. Acute or chronic infectious disease; autoimmune/inflammatory disease, cancer, COPD, anemia, diabetes, psychiatric illness. 4. Non-smokers, prior smokers, or illicit drug users with abstinence \>1 year. 5. 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. 6. 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: 1. Simvastatin 40 mg + placebo once daily (statin only group) for 3 months 2. Simvastatin 40 mg + Epi 50 mg once daily (statin + Epi group) for 3 months
Interventions
DIETARY_SUPPLEMENTPure epicatechin capsules (50mg)
Epicatechin is a compound found naturally in dark chocolate.
DRUGSimvastatin (40mg)
A cholesterol-lowering medication that blocks the production of cholesterol.
OTHERPlacebo
A substance that has no therapeutic effect and will act as a control.
Sponsors
University of California, San Diego
American Heart Association
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Functional Capacity (VO2max) | Baseline and 3 months | Cardiopulmonary exercise protocol will be used to measure VO2max to assess functional capacity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Blood-Based Biomarkers | Baseline and 3 months | Biomarker levels in the blood will be evaluated for correlation with changes in the skeletal muscle mitochondrial structure and function. |
| Changes in Blood-Based Biomarkers-Low Density Lipoprotein Particles | Baseline and 3 months | Biomarker levels in the blood will be evaluated for correlation with changes in the skeletal muscle mitochondrial structure and function in nmol/L. |
| Changes in Triglycerides/HDL | Baseline and 3 months | TG/HDL is a calculated index used as a surrogate marker for insulin resistance, derived by dividing fasting triglyceride level by HDL cholesterol level (both typically measured in mg/dL). Lower ratios indicate healthier insulin sensitivity, while higher ratios indicate greater insulin resistance and cardiometabolic risk. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORPam Taub, M.D.
University of California, San Diego
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.38 years STANDARD_DEVIATION 11.46 |
| BMI (kg/m^2) | 28.91 kg/m2 STANDARD_DEVIATION 0.68 |
| Body weight (kg) | 87.48 kg STANDARD_DEVIATION 2.79 |
| Cholesterol (mg/dL) | 247.7 mg/dL STANDARD_DEVIATION 12.18 |
| Cholesterol non-HDL (mg/dL) | 193.9 mg/dL STANDARD_DEVIATION 13.7 |
| HDL (mg/dL) | 45.83 mg/dL STANDARD_DEVIATION 0.1131 |
| LDL (mg/dL) | 162 mg/dL STANDARD_DEVIATION 8.9 |
| LDL particle number | 1887 nmol/L STANDARD_DEVIATION 197.9 |
| Race and Ethnicity Not Collected | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 9 Participants |
| Small LDL particle number | 1007 nmol/L STANDARD_DEVIATION 60.14 |
| Triglycerides | 234.4 mg/dL STANDARD_DEVIATION 28.64 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 11 |
| other Total, other adverse events | 0 / 8 | 0 / 11 |
| serious Total, serious adverse events | 0 / 8 | 0 / 11 |
Outcome results
None listed