NCT04507373

7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin Associated Adverse Muscle Events

7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Over 40 million Americans take statins to reduce their risk of atherosclerotic cardiovascular disease (ASCVD). Unfortunately, 10 to 20% stop taking them due to statin-associated muscle symptoms (e.g. pain, aches, weakness, cramps, or stiffness) (1, 2). The pathophysiology of these statin-associated muscle symptoms (SAMS) has remained elusive. Consequently, no objective diagnostic method exists, causing confusion for patient and providers since muscle symptoms can often be multifactorial.

Detailed description

The overall objectives of this project are to identify the underlying cause of SAMS and establish an in-vivo imaging technique to detect SAMS. The central hypothesis of this pro-posal is that statins directly inhibit mitochondrial function in SAMS patients. Our rationale is based on our own preliminary data indicating that simvastatin - the most common statin to cause SAMS - can directly inhibit oxidative phosphorylation (OXPHOS) in mice. Since such changes can be detected in vivo in humans utilizing 31P magnetic resonance spectroscopy (MRS) techniques, the investigators will use a state-of-the art 7 Tesla (7T) MRS instrument to study the so-leus muscles of SAMS patients. Additionally, the investigators will validate the MRS findings by doing func-tional studies in muscle biopsy specimens. The investigators propose double-blind randomized, placebo-controlled pilot study in 15 SAMS pa-tients and 15 controls. Study participants will be treated with simvastatin 40 mg daily or place-bo for 10 weeks. The investigators will perform 7T MRS of soleus muscles at randomization and either at first complaint of muscle symptoms or at the end of 10 weeks if no muscle symptoms occur, whichever occurs first. Quadriceps muscle biopsies will also be done immediately following the second MRS scan.

Conditions

• Muscle Cramp
• Ache
• Weakness, Muscle
• Statin Adverse Reaction

Interventions

Type	Name	Description
DRUG	Simvastatin 40mg	40mg oral daily for 10 weeks

Timeline

• Start date: 2018-08-17
• Primary completion: 2021-12-20
• Completion: 2021-12-20
• First posted: 2020-08-11
• Last updated: 2023-02-14
• Results posted: 2023-02-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study