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

NCT02490527 | Completed DMC

• 1 other identifier: UCSD IRB 150171
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Statin Intolerance

Keywords

myopathy; muscular weakness; cramping; fatigue

Outcome Measures

Primary Outcomes (1)

• Changes in Functional Capacity

  Cardiopulmonary exercise protocol will be used to measure VO2max to assess functional capacity.

  Baseline and 3 months

Other Outcomes (2)

• Changes in Blood-Based Biomarkers

  Baseline and 3 months

• Composite Outcome: Changes in Skeletal Muscle Structure and Protein Levels

  Baseline and 3 months

Study Arms (2)

Statin only

PLACEBO COMPARATOR

The subject will consume simvastatin (40mg) and placebo once daily for 3 months.

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.

Dietary Supplement: Pure epicatechin capsules (50mg); Drug: Simvastatin (40mg)

Interventions

Pure epicatechin capsules (50mg) DIETARY_SUPPLEMENT

Epicatechin is a compound found naturally in dark chocolate.

Statin and epicatechin

Simvastatin (40mg) DRUG

A cholesterol-lowering medication that blocks the production of cholesterol.

Statin and epicatechin; Statin only

Placebo OTHER

A substance that has no therapeutic effect and will act as a control.

Statin only

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be between 30-75 years of age
• LDL\>100mg/dL (or on drug treatment)
• VO2 max greater than 25 ml/kg/min

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• American Heart Association: collaborator

Study Sites (1)

University of California, San Diego

La Jolla, California, 92093, United States

Location

Related Publications (10)

• 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.

  PMID: 22376256 BACKGROUND

• Yamazaki 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.

  PMID: 20579545 BACKGROUND

• Nogueira 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.

  PMID: 21788351 BACKGROUND

• Ramirez-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.

  PMID: 22833114 BACKGROUND

• Ramirez-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.

  PMID: 23870648 BACKGROUND

• Taub 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.

  PMID: 23642227 BACKGROUND

• Barnett 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.

  PMID: 25598082 BACKGROUND

• Ortiz-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.

  PMID: 25281837 BACKGROUND

• Gutierrez-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.

  PMID: 24314870 BACKGROUND

• Ormiston 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.

  PMID: 40387782 DERIVED

MeSH Terms

Conditions

Muscular Diseases; Muscle Weakness; Spasm; Fatigue

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Pam Taub, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 17, 2015
• First Posted: July 7, 2015
• Study Start: June 1, 2015
• Primary Completion: July 28, 2021
• Study Completion: July 28, 2021
• Last Updated: September 29, 2021

Record last verified: 2021-09

Locations

US (1)