Muscle Characteristics Associated With Statin Therapy
21. maj 2015 opdateret af: Scripps Health
The purpose of this study is to investigate the mechanism of statin-related myopathy by evaluating muscle samples before and after statin exposure.
Studieoversigt
Status
Trukket tilbage
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
California
-
San Diego, California, Forenede Stater, 92103
- Scripps-Mercy Hospital
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
21 år til 90 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Beskrivelse
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.
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: Statin exposure
Subjects' endpoints will be measured before and after one to eight months of statin exposure.
|
simvastatin 80 mg PO daily for one to eight months.
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Atrogin-1 expression.
Tidsramme: One to eight months.
|
One to eight months.
|
|
Intramuscular Ras level.
Tidsramme: One to eight months.
|
One to eight months.
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Intramuscular Coenzyme Q10 level.
Tidsramme: One to eight months.
|
One to eight months.
|
|
Intramuscular mitochondrial to nuclear DNA ratio.
Tidsramme: One to eight months.
|
One to eight months.
|
|
Intramuscular geranylgeranylpyrophosphate.
Tidsramme: One to eight months.
|
One to eight months.
|
|
PPAR-gamma coactivator-1-alpha expression.
Tidsramme: One to eight months.
|
One to eight months.
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Paul S Phillips, MD, Scripps Health
- Ledende efterforsker: Tam H Truong, MD, Scripps Health
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- 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.
- 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. Erratum In: Circulation. 2004 Aug 10;110(6):763.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. november 2009
Primær færdiggørelse (Forventet)
1. juni 2011
Studieafslutning (Forventet)
1. juni 2011
Datoer for studieregistrering
Først indsendt
5. oktober 2009
Først indsendt, der opfyldte QC-kriterier
6. oktober 2009
Først opslået (Skøn)
7. oktober 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
22. maj 2015
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
21. maj 2015
Sidst verificeret
1. maj 2015
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- MCAST
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .