Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy
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Purpose
A major contributor to frailty and immobility in the elderly is the age related loss of muscle mass (sarcopenia). Cardiovascular disease (CVD) is the leading cause of mortality in the elderly, with high blood cholesterol and lipids being the major modifiable risk factor. Statins reduce blood cholesterol, but muscle related pain, tenderness and discomfort (myopathy) is an adverse event associated with statin therapy, with older people being at a much greater risk. Statin myopathy presents as muscle aches and weakness, with or without evidence of muscle damage; however the underlying mechanisms responsible for these symptoms are poorly understood. Using an animal model, the applicants have shown the main pathway regulating muscle protein synthesis is inhibited in statin myopathy, and genes regulating muscle protein breakdown, the inhibition of muscle carbohydrate use and inflammation are dramatically increased. Therefore we wish to determine whether these changes are seen in the muscle of older people with symptoms of statin myopathy, and whether this is associated with lower muscle mass and impaired muscle function compared with older people with no history of statin use. Identification of the mechanisms involved in statin myopathy could lead to effective therapy for older people unable to tolerate statins.
| Condition |
|---|
|
Myopathy |
| Study Type: | Observational |
| Study Design: | Observational Model: Cohort Time Perspective: Cross-Sectional |
| Official Title: | Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy |
- Increase in MAFbx (atrophy gene)mRNA expression in those on Statin therapy [ Time Frame: On study visit ] [ Designated as safety issue: Yes ]
- Expression of genes that regulate muscle protein balance. [ Time Frame: Before, 2 hours after aminoacid tracer infusion and 2 hours after a 40mU/m2 hyperinsulinaemic, euglycaemic clamp with aminoacid infusion (10g/h) ] [ Designated as safety issue: No ]
Biospecimen Retention: Samples With DNA
Plasma, Muscle biopsy, Serum & Whole blood
| Estimated Enrollment: | 30 |
| Study Start Date: | June 2009 |
| Estimated Study Completion Date: | December 2012 |
| Estimated Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Groups/Cohorts |
|---|
|
Statin
Men aged 65-75yr on Simvastatin therapy presenting with muscle soreness
|
|
Control
Men, aged 65-75yr not on Statin therapy
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 65 Years to 75 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
Community Sample
Inclusion Criteria:
- Male
- 65-75yrs
- Simvastatin use with muscle soreness or no statin use
- Residing in Nottinghamshire area
Exclusion Criteria:
- Clotting disorders or previous CVA/TIA/DVT
- Metabolic disease e.g. diabetes, thyroid dysfunction
- Inflammatory conditions e.g. Rheumatoid Arthritis, Crohn's Disease
- Tobacco smoker
- Lower limb circulation problems e.g. Claudication
- Epilepsy
- Renal pathology
- Respiratory problems including Asthma
Contacts and Locations| Contact: Marimuthu Kanagaraj, MRCS | +44(0)115 8230199 | marimuthu.kanagaraj@nottingham.ac.uk |
| Contact: Joanne E Mallinson, PhD | +44(0)115 8230578 | joanne.mallinson@nottingham.ac.uk |
| United Kingdom | |
| David Greenfield Physiology Laboratories | Recruiting |
| Nottingham, Nottinghamshire, United Kingdom, NG72UH | |
| Principal Investigator: Paul L Greenhaff, PhD | |
| Principal Investigator: | Paul L Greenhaff, PhD | University of Nottingham |
More Information
No publications provided
| Responsible Party: | University of Nottingham |
| ClinicalTrials.gov Identifier: | NCT01047163 History of Changes |
| Other Study ID Numbers: | RB03DR |
| Study First Received: | January 11, 2010 |
| Last Updated: | December 3, 2012 |
| Health Authority: | United Kingdom: Research Ethics Committee |
Keywords provided by University of Nottingham:
|
Muscle soreness Simvastatin Men Muscle Atrophy |
Additional relevant MeSH terms:
|
Muscular Diseases Musculoskeletal Diseases Neuromuscular Diseases Nervous System Diseases Hydroxymethylglutaryl-CoA Reductase Inhibitors Anticholesteremic Agents Hypolipidemic Agents |
Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Enzyme Inhibitors Lipid Regulating Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on May 19, 2013