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Muscle Characteristics Associated With Statin Therapy

Primary Purpose

Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myopathy

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

simvastatin

About this trial

This is an interventional basic science trial for Hydroxymethylglutaryl-CoA Reductase Inhibitors focused on measuring Statin, Myopathy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atrogin-1

Eligibility Criteria

21 Years - 90 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Scripps-Mercy Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Statin exposure

Arm Description

Subjects' endpoints will be measured before and after one to eight months of statin exposure.

Outcomes

Primary Outcome Measures

Atrogin-1 expression.

Intramuscular Ras level.

Secondary Outcome Measures

Intramuscular Coenzyme Q10 level.

Intramuscular mitochondrial to nuclear DNA ratio.

Intramuscular geranylgeranylpyrophosphate.

PPAR-gamma coactivator-1-alpha expression.

Full Information

NCT ID

NCT00990834

First Posted

October 5, 2009

Last Updated

May 21, 2015

Sponsor

Scripps Health

1. Study Identification

Unique Protocol Identification Number

NCT00990834

Brief Title

Muscle Characteristics Associated With Statin Therapy

Official Title

Muscle Characteristics Associated With Statin Therapy

Study Type

Interventional

2. Study Status

Record Verification Date

May 2015

Overall Recruitment Status

Withdrawn

Why Stopped

Unable to recruit subjects.

Study Start Date

November 2009 (undefined)

Primary Completion Date

June 2011 (Anticipated)

Study Completion Date

June 2011 (Anticipated)

3. Sponsor/Collaborators

Name of the Sponsor

Scripps Health

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hydroxymethylglutaryl-CoA Reductase Inhibitors, Myopathy

Keywords

Statin, Myopathy, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atrogin-1

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Statin exposure

Arm Type

Experimental

Arm Description

Subjects' endpoints will be measured before and after one to eight months of statin exposure.

Intervention Type

Drug

Intervention Name(s)

simvastatin

Other Intervention Name(s)

Zocor

Intervention Description

simvastatin 80 mg PO daily for one to eight months.

Primary Outcome Measure Information:

Title

Atrogin-1 expression.

Time Frame

One to eight months.

Title

Intramuscular Ras level.

Time Frame

One to eight months.

Secondary Outcome Measure Information:

Title

Intramuscular Coenzyme Q10 level.

Time Frame

One to eight months.

Title

Intramuscular mitochondrial to nuclear DNA ratio.

Time Frame

One to eight months.

Title

Intramuscular geranylgeranylpyrophosphate.

Time Frame

One to eight months.

Title

PPAR-gamma coactivator-1-alpha expression.

Time Frame

One to eight months.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

90 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tam H Truong, MD

Organizational Affiliation

Scripps Health

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Paul S Phillips, MD

Organizational Affiliation

Scripps Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Scripps-Mercy Hospital

City

San Diego

State/Province

California

ZIP/Postal Code

92103

Country

United States

12. IPD Sharing Statement

Citations:

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7566020

Citation

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Muscle Characteristics Associated With Statin Therapy

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