Muscle Characteristics Associated With Statin Therapy

This study has been withdrawn prior to enrollment.
(Unable to recruit subjects.)
Sponsor:
Information provided by:
Scripps Health
ClinicalTrials.gov Identifier:
NCT00990834
First received: October 5, 2009
Last updated: July 26, 2011
Last verified: July 2011
  Purpose

The purpose of this study is to investigate the mechanism of statin-related myopathy by evaluating muscle samples before and after statin exposure.


Condition Intervention
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Myopathy
Drug: simvastatin

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Muscle Characteristics Associated With Statin Therapy

Resource links provided by NLM:


Further study details as provided by Scripps Health:

Primary Outcome Measures:
  • Atrogin-1 expression. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]
  • Intramuscular Ras level. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Intramuscular Coenzyme Q10 level. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]
  • Intramuscular mitochondrial to nuclear DNA ratio. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]
  • Intramuscular geranylgeranylpyrophosphate. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]
  • PPAR-gamma coactivator-1-alpha expression. [ Time Frame: One to eight months. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: November 2009
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Statin exposure
Subjects' endpoints will be measured before and after one to eight months of statin exposure.
Drug: simvastatin
simvastatin 80 mg PO daily for one to eight months.
Other Name: Zocor

Detailed Description:

Statins have been proven to reduce cardiovascular events and mortality in large clinical trials but remain underutilized partly due to the associated myopathy. Severe reactions manifested as rhabdomyolysis are rare but myalgia is commonly noted in clinical practice. The pathophysiology of these events remains obscure. Previous studies suggest that statins block the downstream products (such as cellular signaling molecules) of the mevalonate pathway needed for normal muscle function. Other studies show that statins are associated with gene expressions involved in muscle damage such as atrogin-1. We will quantify these entities pre and post statin therapy to better understand these reactions.

  Eligibility

Ages Eligible for Study:   21 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Primary surgeon's permission.
  • Patient is > 21 years of age.
  • Patient will go through a two phase surgery with the two procedures one to eight months apart.
  • Patient or representative understands the nature of the study.
  • Normal thyroid stimulating hormone (TSH).
  • LDL-cholesterol > 100 mg/dL or highly sensitive C-reactive protein (hsCRP) > 2.0.
  • One of the following risk factors: male > 45 year old or female > 55 year old, smoker, hypertension, first degree family history of coronary artery disease < 55 year old, HDL <40 mg/dL, chronic kidney disease, diabetes mellitus, previous TIA or stroke, previous coronary artery disease.

Exclusion Criteria:

  • Has been on a lipid-lowering medication previously.
  • Severe illness (e.g. trauma or sepsis) more than 24 hours before obtaining the first biopsy.
  • Less than a 10% reduction of LDL after 3 months of therapy (indicative of non-adherence).
  • Contraindications to statins such as liver failure.
  • History of underlying muscle disorder.
  • Taking amiodarone.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990834

Locations
United States, California
Scripps-Mercy Hospital
San Diego, California, United States, 92103
Sponsors and Collaborators
Scripps Health
Investigators
Principal Investigator: Tam H Truong, MD Scripps Health
Principal Investigator: Paul S Phillips, MD Scripps Health
  More Information

Publications:

Responsible Party: Truong, H. Tam, MD, Scripps Mercy Hospital
ClinicalTrials.gov Identifier: NCT00990834     History of Changes
Other Study ID Numbers: MCAST
Study First Received: October 5, 2009
Last Updated: July 26, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Scripps Health:
Statin
Myopathy
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atrogin-1

Additional relevant MeSH terms:
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Simvastatin
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on August 20, 2014