Back to results7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin Associated Adverse Muscle Events
Primary Purpose
Muscle Cramp, Ache, Weakness, Muscle
Status
Terminated
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Simvastatin 40mg
Sponsored by
About this trial
This is an interventional basic science trial for Muscle Cramp
Eligibility Criteria
Inclusion
• Adults, age > 18 ys or < 80 yrs. Patients reporting complaints of statin-associated muscle symptoms, aches, weakness, cramps, or stiffness in the legs.
Exclusion Criteria
- 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.
Sites / Locations
- UT Southwestern Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Placebo
Simvastatin 40mg
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Full Information
NCT ID
NCT04507373
First Posted
January 31, 2019
Last Updated
January 23, 2023
Sponsor
University of Texas Southwestern Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT04507373
Brief Title
7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin Associated Adverse Muscle Events
Official Title
7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Terminated
Why Stopped
No grant obtained. Enrolled participants were not assigned to the intervention and was study terminated
Study Start Date
August 17, 2018 (Actual)
Primary Completion Date
December 20, 2021 (Actual)
Study Completion Date
December 20, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Cramp, Ache, Weakness, Muscle, Statin Adverse Reaction
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Double Blind
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Simvastatin 40mg
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Simvastatin 40mg
Intervention Description
40mg oral daily for 10 weeks
Primary Outcome Measure Information:
Title
The Mitochondrial Changes In Muscles During Statin Use
Description
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
Time Frame
10 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion
• Adults, age > 18 ys or < 80 yrs. Patients reporting complaints of statin-associated muscle symptoms, aches, weakness, cramps, or stiffness in the legs.
Exclusion Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zahid Ahmad, M.D.
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Learn more about this trial
7T Magnetic Resonance Spectroscopy and Skeletal Muscle Biopsy Findings in Statin Associated Adverse Muscle Events
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