Muscle Characteristics Associated With Statin Therapy

NCT ID: NCT00990834

Last Updated: 2015-05-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2009-11-30

Study Completion Date

2011-06-30

Brief Summary

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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

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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.

Conditions

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Hydroxymethylglutaryl-CoA Reductase Inhibitors Myopathy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Statin exposure

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

Group Type EXPERIMENTAL

simvastatin

Intervention Type DRUG

simvastatin 80 mg PO daily for one to eight months.

Interventions

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simvastatin

simvastatin 80 mg PO daily for one to eight months.

Intervention Type DRUG

Other Intervention Names

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Zocor

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Scripps Health

OTHER

Sponsor Role lead

Responsible Party

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Scripps Mercy Hospital

Principal Investigators

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Tam H Truong, MD

Role: PRINCIPAL_INVESTIGATOR

Scripps Health

Paul S Phillips, MD

Role: PRINCIPAL_INVESTIGATOR

Scripps Health

Locations

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Scripps-Mercy Hospital

San Diego, California, United States

Site Status

Countries

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United States

References

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Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, McKillop JH, Packard CJ. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995 Nov 16;333(20):1301-7. doi: 10.1056/NEJM199511163332001.

Reference Type BACKGROUND
PMID: 7566020 (View on PubMed)

Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998 Nov 5;339(19):1349-57. doi: 10.1056/NEJM199811053391902.

Reference Type BACKGROUND
PMID: 9841303 (View on PubMed)

Kashani A, Phillips CO, Foody JM, Wang Y, Mangalmurti S, Ko DT, Krumholz HM. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006 Dec 19;114(25):2788-97. doi: 10.1161/CIRCULATIONAHA.106.624890. Epub 2006 Dec 11.

Reference Type BACKGROUND
PMID: 17159064 (View on PubMed)

Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients--the PRIMO study. Cardiovasc Drugs Ther. 2005 Dec;19(6):403-14. doi: 10.1007/s10557-005-5686-z.

Reference Type BACKGROUND
PMID: 16453090 (View on PubMed)

Flint OP, Masters BA, Gregg RE, Durham SK. Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Toxicol Appl Pharmacol. 1997 Jul;145(1):91-8. doi: 10.1006/taap.1997.8131.

Reference Type BACKGROUND
PMID: 9221828 (View on PubMed)

Nishimoto T, Ishikawa E, Anayama H, Hamajyo H, Nagai H, Hirakata M, Tozawa R. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs. Toxicol Appl Pharmacol. 2007 Aug 15;223(1):39-45. doi: 10.1016/j.taap.2007.05.005. Epub 2007 May 24.

Reference Type BACKGROUND
PMID: 17599378 (View on PubMed)

Matzno S, Yasuda S, Juman S, Yamamoto Y, Nagareya-Ishida N, Tazuya-Murayama K, Nakabayashi T, Matsuyama K. Statin-induced apoptosis linked with membrane farnesylated Ras small G protein depletion, rather than geranylated Rho protein. J Pharm Pharmacol. 2005 Nov;57(11):1475-84. doi: 10.1211/jpp.57.11.0014.

Reference Type BACKGROUND
PMID: 16259781 (View on PubMed)

Young JM, Florkowski CM, Molyneux SL, McEwan RG, Frampton CM, George PM, Scott RS. Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia. Am J Cardiol. 2007 Nov 1;100(9):1400-3. doi: 10.1016/j.amjcard.2007.06.030. Epub 2007 Aug 16.

Reference Type BACKGROUND
PMID: 17950797 (View on PubMed)

Draeger A, Monastyrskaya K, Mohaupt M, Hoppeler H, Savolainen H, Allemann C, Babiychuk EB. Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. J Pathol. 2006 Sep;210(1):94-102. doi: 10.1002/path.2018.

Reference Type BACKGROUND
PMID: 16799920 (View on PubMed)

Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Pasternak RC, Smith SC Jr, Stone NJ; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39. doi: 10.1161/01.CIR.0000133317.49796.0E.

Reference Type BACKGROUND
PMID: 15249516 (View on PubMed)

Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O'Brien E, Ostergren J; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003 Apr 5;361(9364):1149-58. doi: 10.1016/S0140-6736(03)12948-0.

Reference Type BACKGROUND
PMID: 12686036 (View on PubMed)

Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006 Mar 23;354(12):1264-72. doi: 10.1056/NEJMoa054013.

Reference Type BACKGROUND
PMID: 16554528 (View on PubMed)

Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 2007 Dec;117(12):3940-51. doi: 10.1172/JCI32741.

Reference Type BACKGROUND
PMID: 17992259 (View on PubMed)

Shishehbor MH, Patel T, Bhatt DL. Using statins to treat inflammation in acute coronary syndromes: Are we there yet? Cleve Clin J Med. 2006 Aug;73(8):760-6. doi: 10.3949/ccjm.73.8.760.

Reference Type BACKGROUND
PMID: 16913201 (View on PubMed)

Other Identifiers

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MCAST

Identifier Type: -

Identifier Source: org_study_id

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