Statin IntoleranceNCT02490527
Effects of Epicatechin on Statins for Mitochondrial Dysfunction and Impaired Exercise Capacity
A study testing Pure epicatechin capsules (50mg) and Simvastatin (40mg) in people with Statin Intolerance, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Statin Intolerance
- What is being tested?
- Pure epicatechin capsules (50mg) and Simvastatin (40mg)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to 28 Jul 2021
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92093
About this study
Official title: Effects of Epicatechin on Patients With Statin-induced Mitochondrial Dysfunction and Impaired Exercise Capacity
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.
Read the 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
- Conditions
- Statin Intolerance
- Being tested
- Pure epicatechin capsules (50mg), Simvastatin (40mg), Placebo
- Keywords
- myopathy, muscular weakness, cramping, fatigue
- Medical subject headings
- Muscular Diseases, Muscle Weakness, Spasm, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pure epicatechin capsules (50mg)Dietary supplement
Epicatechin is a compound found naturally in dark chocolate.
Simvastatin (40mg)Drug
A cholesterol-lowering medication that blocks the production of cholesterol.
PlaceboOther
A substance that has no therapeutic effect and will act as a control.
| Study group | Role | What they receive |
|---|---|---|
| Statin only | Placebo comparator | The subject will consume simvastatin (40mg) and placebo once daily for 3 months. Receives: Drug: Simvastatin (40mg); Other: Placebo |
| Statin and epicatechin | Experimental | The subject will consume simvastatin (40mg) and pure epicatechin capsules (50mg) once daily for 3 months. Receives: Dietary Supplement: Pure epicatechin capsules (50mg); Drug: Simvastatin (40mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Functional Capacity (VO2max)
Cardiopulmonary exercise protocol will be used to measure VO2max to assess functional capacity.
Measured: Baseline and 3 months
Secondary outcomes (3)
Changes in Blood-Based Biomarkers
Biomarker levels in the blood will be evaluated for correlation with changes in the skeletal muscle mitochondrial structure and function.
Measured: Baseline and 3 months
Changes in Blood-Based Biomarkers-Low Density Lipoprotein Particles
Biomarker levels in the blood will be evaluated for correlation with changes in the skeletal muscle mitochondrial structure and function in nmol/L.
Measured: Baseline and 3 months
Changes in Triglycerides/HDL
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.
Measured: Baseline and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2015 (estimated)
- Study startJun 2015
- Primary completion28 Jul 2021
- Study completion28 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Statin IntoleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association
- Responsible party
- Principal investigator, Pam Taub, MD, University of California, San Diego
- Investigators
- Pam Taub, M.D., Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02490527
- Sponsor's protocol ID
- UCSD IRB 150171
- Status last verified
- Aug 2024
- First submitted
- 17 Jun 2015
- Last updated
- 31 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7. doi: 10.1111/j.1752-8062.2011.00357.x. Epub 2011 Nov 7.
PubMed 22376256Yamazaki KG, Taub PR, Barraza-Hidalgo M, Rivas MM, Zambon AC, Ceballos G, Villarreal FJ. Effects of (-)-epicatechin on myocardial infarct size and left ventricular remodeling after permanent coronary occlusion. J Am Coll Cardiol. 2010 Jun 22;55(25):2869-76. doi: 10.1016/j.jacc.2010.01.055.
PubMed 20579545Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal FJ, Hogan MC, Malek MH. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011 Sep 15;589(Pt 18):4615-31. doi: 10.1113/jphysiol.2011.209924. Epub 2011 Jul 25.
PubMed 21788351Ramirez-Sanchez I, Nogueira L, Moreno A, Murphy A, Taub P, Perkins G, Ceballos GM, Hogan M, Malek M, Villarreal F. Stimulatory effects of the flavanol (-)-epicatechin on cardiac angiogenesis: additive effects with exercise. J Cardiovasc Pharmacol. 2012 Nov;60(5):429-38. doi: 10.1097/FJC.0b013e318269ae0d.
PubMed 22833114Ramirez-Sanchez I, Taub PR, Ciaraldi TP, Nogueira L, Coe T, Perkins G, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. (-)-Epicatechin rich cocoa mediated modulation of oxidative stress regulators in skeletal muscle of heart failure and type 2 diabetes patients. Int J Cardiol. 2013 Oct 9;168(4):3982-3990. doi: 10.1016/j.ijcard.2013.06.089. Epub 2013 Jul 17.
PubMed 23870648Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Gonzalez-Basurto S, Coral-Vazquez R, Perkins G, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Perturbations in skeletal muscle sarcomere structure in patients with heart failure and type 2 diabetes: restorative effects of (-)-epicatechin-rich cocoa. Clin Sci (Lond). 2013 Oct;125(8):383-9. doi: 10.1042/CS20130023.
PubMed 23642227Barnett CF, Moreno-Ulloa A, Shiva S, Ramirez-Sanchez I, Taub PR, Su Y, Ceballos G, Dugar S, Schreiner G, Villarreal F. Pharmacokinetic, partial pharmacodynamic and initial safety analysis of (-)-epicatechin in healthy volunteers. Food Funct. 2015 Mar;6(3):824-33. doi: 10.1039/c4fo00596a.
PubMed 25598082Ortiz-Vilchis P, Yamazaki KG, Rubio-Gayosso I, Ramirez-Sanchez I, Calzada C, Romero-Perez D, Ortiz A, Meaney E, Taub P, Villarreal F, Ceballos G. Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling. Eur J Pharmacol. 2014 Dec 5;744:76-82. doi: 10.1016/j.ejphar.2014.09.042. Epub 2014 Oct 2.
PubMed 25281837Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan MC, Henry RR, Meaney E, Villarreal F, Ceballos G, Ramirez-Sanchez I. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. J Nutr Biochem. 2014 Jan;25(1):91-4. doi: 10.1016/j.jnutbio.2013.09.007. Epub 2013 Oct 18.
PubMed 24314870Ormiston CK, Pazargadi A, Rosander A, Ceballos G, Villarreal F, Taub PR. Enhancement of Statin Effects on Lipid Lowering and Reduction of Cardiovascular Risk Score by (-)-Epicatechin in Proof-of-Concept Pilot Study. Clin Transl Sci. 2025 May;18(5):e70236. doi: 10.1111/cts.70236.
PubMed 40387782