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

NCT04507373 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: STU 072016-015
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• The Mitochondrial Changes In Muscles During Statin Use

  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

  10 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Simvastatin 40mg

Simvastatin 40mg

ACTIVE COMPARATOR

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.

Drug: Simvastatin 40mg

Interventions

Simvastatin 40mg DRUG

40mg oral daily for 10 weeks

Placebo; Simvastatin 40mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults, age \> 18 ys or \< 80 yrs. Patients reporting complaints of statin-associated muscle symptoms, aches, weakness, cramps, or stiffness in the legs.

You may not qualify if:

• Patient who drink large quantities of grapefruit juice (\> 1 quart daily).
• Patients on the following drugs for which the FDA has issued restrictions for using simvastatin 40 mg daily do to an increased risk of severe muscle injury such as itraconazole, posaconazole, ketoconazole, erythromycin, clarithromycin, telithromycin, HIV-1 protease inhibitors, nefazodone, gemfibrozil, cyclosporine, danazol, amiodarone, amlodipine, ranolazine, and verapamil.
• Patients with muscle-related pain that is not related to statin-use (e.g. muscle aches from strain or trauma) or remains unexplained.
• Any patients with underlying non-statin related muscle disorders.
• Presence of any clinically significant uncontrolled endocrine disease known to influence serum lipids or lipoproteins.
• Conditions of severe acute vascular stress (acute coronary syndrome, ischemic stroke, or major vascular surgery) within prior 3 months.
• Any patients with a history of severe or life-threatening reactions to statins including rhabdomyolysis (defined as evidence of organ damage with CK \>10,000 IU/L), CK elevation \> 10 times the upper limit of normal, cognitive decline, transaminitis, or allergic reactions.
• History of fibromyalgia or rheumatologic disease with symptoms that may be confounded with statin-related muscle complaints.
• Patients unable to maintain their current activity level or planning to increase their activity level (e.g. new exercise regimen). Such changes may have acute effects on muscle metabolism.
• Pregnant or breast-feeding women. Statins are teratogenic, and the effects of high magnetic fields on a fetus are unknown.
• Women of reproductive age not on effective contraception. Adequate contraceptive measures include intrauterine device (IUD); bilateral tubal ligation; condom or diaphragm plus either contraceptive sponge, foam or jelly.
• Any person with implanted metal, because of MRS safety.
• Use of any active investigational drugs within 1 month or 5 half-lives, whichever is longer.
• History of antibodies to HMGCoA.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Muscle Cramp; Pain; Muscle Weakness

Interventions

Simvastatin

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Zahid Ahmad
• Organization: UT Southwestern Medical Center

ZAHID.AHMAD@UTSouthwestern.edu

214/648-2377

Study Officials

• Zahid Ahmad, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double Blind
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: August 11, 2020
• Study Start: August 17, 2018
• Primary Completion: December 20, 2021
• Study Completion: December 20, 2021
• Last Updated: February 14, 2023
• Results First Posted: February 14, 2023

Record last verified: 2023-01

Locations

US (1)