Maintenance of Muscle Mass in Older People: the Negative Impact of Statin Therapy

NCT01047163 | Completed

• 1 other identifier: RB03DR
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myopathy

Keywords

Muscle soreness; Simvastatin; Men; Muscle Atrophy

Outcome Measures

Primary Outcomes (1)

• Increase in MAFbx (atrophy gene) mRNA expression in those on Statin therapy

  On study visit

Secondary Outcomes (1)

• Expression of genes that regulate muscle protein balance.

  Before, 2 hours after aminoacid tracer infusion and 2 hours after a 40 mU/m2 hyperinsulinaemic, euglycaemic clamp with aminoacid infusion (10g/h)

Study Arms (2)

Statin

Men aged 65-75yr on Simvastatin therapy presenting with muscle soreness

Control

Men, aged 65-75yr not on Statin therapy

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community Sample

You may qualify if:

• Male
• yrs
• Simvastatin use with muscle soreness or no statin use
• Residing in Nottinghamshire area

You may not qualify if:

• Clotting disorders or previous Cerebral Vascular Accident /Transient Ischaemic Attack /Deep Vein Thrombosis
• 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

Sponsors & Collaborators

• University of Nottingham: lead
• The Dunhill Medical Trust: collaborator

Study Sites (1)

David Greenfield Physiology Laboratories

Nottingham, Nottinghamshire, NG72UH, United Kingdom

Location

Related Publications (4)

• Nichols GA, Koro CE. Does statin therapy initiation increase the risk for myopathy? An observational study of 32,225 diabetic and nondiabetic patients. Clin Ther. 2007 Aug;29(8):1761-70. doi: 10.1016/j.clinthera.2007.08.022.

  PMID: 17919557 BACKGROUND

• Mallinson JE, Constantin-Teodosiu D, Sidaway J, Westwood FR, Greenhaff PL. Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol. 2009 Jan 15;587(1):219-30. doi: 10.1113/jphysiol.2008.164699. Epub 2008 Nov 10.

  PMID: 19001041 BACKGROUND

• 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.

  PMID: 17992259 BACKGROUND

• Mallinson JE, Marimuthu K, Murton A, Selby A, Smith K, Constantin-Teodosiu D, Rennie MJ, Greenhaff PL. Statin myalgia is not associated with reduced muscle strength, mass or protein turnover in older male volunteers, but is allied with a slowing of time to peak power output, insulin resistance and differential muscle mRNA expression. J Physiol. 2015 Mar 1;593(5):1239-57. doi: 10.1113/jphysiol.2014.285577. Epub 2015 Jan 26.

  PMID: 25620655 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, Muscle biopsy, Serum \& Whole blood

MeSH Terms

Conditions

Muscular Diseases; Myalgia; Multiple Endocrine Neoplasia Type 1; Muscular Atrophy

Condition Hierarchy (Ancestors)

Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Musculoskeletal Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Neuromuscular Manifestations; Atrophy; Pathological Conditions, Anatomical

Study Officials

• Paul L Greenhaff, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 12, 2010
• Study Start: June 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: December 1, 2012
• Last Updated: April 27, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)