NIRS to Diagnose SAMS

Statin Adverse Reaction Clinical Trial

Official title: Near Infrared Spectroscopy to Diagnose Statin-Associated Muscle Symptoms

Status Active, not recruiting

Clinical Trial Summary

This proposal seeks to determine whether near infrared spectroscopy (NIRS) can differentiate between patients with confirmed SAMS and those with non-specific muscle complaints. NIRS is a non-invasive technique of assessing skeletal muscle tissue oxygenation and mitochondrial function. Mitochondrial dysfunction is a possible cause of SAMS, but NIRS has never been evaluated as a diagnostic tool for SAMS. Investigators will enroll 40 patients with a history of SAMS in an 8 wk randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo separated by a 4 wk washout phase. Tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol before and after each treatment period. Investigators will query patients about muscle complaints weekly during both phases of the study with a validated survey to assess muscle pain. Investigators will classify patients as testing positive for SAMS if they report pain on simvastatin and not placebo. Investigators hypothesize that these patients, vs. patients experiencing pain on both treatments, placebo, or neither treatment, will be distinguished by reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.

Clinical Trial Description

Study Overview: Forty patients with possible SAMS will be recruited from the Cholesterol Management Center at Hartford Hospital, advertisements and contact with physicians' offices. Subjects will be withdrawn from all statin lipid lowering medications for at least 4 weeks. Subjects will then undergo baseline testing (tissue oxygenation will be measured using NIRS during a short handgrip exercise protocol) and be randomized to treatment with simvastatin 20 mg daily or matching placebo for up to 2 months. Subjects will be called weekly to assess symptoms of muscle pain and administer the Brief Pain Inventory (BPI). NIRS measurements will be repeated and treatment (simvastatin or placebo) will be stopped after 2 months or after subjects have experienced muscle symptoms continuously for one week. After 4 weeks washout, subjects will again be randomized to simvastatin or placebo treatment and the monitoring and measurement processes will be repeated (see study schematic below). Those patients developing muscle symptoms during statin treatment but not during placebo treatment will be considered to have confirmed SAMS. Investigators hypothesize that patients with confirmed SAMS will be distinguished from all other patients with reduced tissue oxygenation during simvastatin treatment relative to placebo, demonstrating efficacy of NIRS as a clinical tool that can be eventually used for the diagnosis and ultimately treatment of SAMS.

Study Subjects: Statin myopathic symptoms have been poorly defined in the medical literature. For the purpose of this study, investigators will use similar criteria as the previous CoQ10 in Statin Myopathy Study when recruiting eligible subjects. Subjects will be considered to have had prior statin related complaints and recruited for participation in the study if the following occurred: 1) They developed new myalgia, cramps, or muscle aching during statin treatment; 2) The symptoms resolved within 4 weeks of stopping the statin; 3) The identical symptoms recurred during repeat statin exposure. Investigators will recruit men and women ≥40 yrs of age, since older age is a risk factor for SAMS and 25% of U.S. adults ≥40 yrs report statin use. Investigators will enroll equal numbers of men and women to improve the generalizability of the results. Investigators will not exclude individuals with diagnosed coronary artery disease, peripheral vascular disease, or an elevated CK off treatment<10 upper normal limit (UNL) because spontaneous elevations in CK levels are normal in the general population. During the study, subjects will be contacted by phone weekly to inquire about muscle complaints using the Brief Pain Inventory (Short Form) (BPI-SF). Results will be recorded on paper forms and entered into the database. After 1 week of persistent symptoms or as soon as possible if the patient has intolerable symptoms, the subject will undergo NIRS testing and be taken off study drug. This reduces undue subject burden such that subjects do not have to maintain statin treatment for multiple weeks with pain symptoms. Subjects who do not report recurrent symptoms will be treated for 8 weeks, at which time they will undergo 4 weeks washout and move on to the crossover phase. Subjects will be reimbursed $200 for study. ;

Related Conditions & MeSH terms

• Muscular Diseases
• Skeletal Myopathy
• Statin Adverse Reaction

• NCT number: NCT03653663
• Study type: Interventional
• Source: Hartford Hospital
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: January 1, 2018
• Completion date: July 30, 2020