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

Phase 4

Terminated

• Conditions: Muscle Cramp; Ache; Weakness, Muscle; Statin Adverse Reaction
• Interventions: Drug: Simvastatin 40mg

• Registration Number: NCT04507373
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief 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.

Study Timeline

• Study Start: 2018-08-17
• Study First Submitted: 2019-01-31
• Study First Submitted QC: 2020-08-07
• Study First Posted: 2020-08-11
• Primary Completion: 2021-12-20
• Study Completion: 2021-12-20
• Status Verified: 2023-01
• Results First Submitted: 2023-01-23
• Results First Submitted QC: 2023-01-23
• Last Update Submitted: 2023-01-23
• Results First Posted: 2023-02-14
• Last Update Posted: 2023-02-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Simvastatin 40mg	Following the baseline period, subject will be randomized to receive either simvastatin or an identical placebo at a dose of 40 mg/day for a period of 10 weeks.
Simvastatin 40mg	Simvastatin 40mg	Following the baseline period, subject will be randomized to receive either simvastatin or an identical placebo at a dose of 40 mg/day for a period of 10 weeks.

Primary Outcome Measures

Name	Time	Method
The Mitochondrial Changes In Muscles During Statin Use	10 weeks	Study participants being treated with Simvastatin 40mg daily, or placebo for 10 weeks. Investigators will isolate mitochondrial from muscle biopsy sample and compare mitochondrial oxygen consumption rates, ultrastructural changes, and gene expression

Trial Locations

Locations (1)

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States