7 Tesla MRI Study in Patients With Statin Related Muscle Complaints

Muscle Weakness Clinical Trial

Official title:

7 Tesla MRI Study in Patients With Statin Related Muscle Complaints

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04575090
• Other study ID #: STU 012016-017
• Status: Completed
• Phase: N/A
• Start date: March 5, 2016
• Est. completion date: June 23, 2021

Study information

• Verified date: April 2022
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Roughly 5-10% of statin-treated patients report muscle pain, aches, weakness, cramps, stiffness, or "heaviness" - typically occurring symmetrically in the legs. For healthcare providers, the major diagnostic challenge is to unambiguously link these symptoms to statin use, especially since some patients can have normal serum creatine kinase (CK) levels despite demonstrable weakness and muscle biopsy proven statin-induced myopathy .

No well accepted, standardized, or Food and Drug Administration (FDA)-endorsed diagnostic method exists for statin-induced muscle injury. This lack of an objective diagnostic methodology blocks vertical advancement of the field.

The successful completion of this project will develop in vivo techniques that will provide insight into how statins affect muscle metabolism and help establish a methodology to objectively diagnose muscle injury due to statins. The development of an MRS technique will allow for in-vivo analyses and the data accumulated here will serve as preliminary data for futher extramural funding of studies with much larger sample sizes. Ultimately, this focus of research will lead to improved diagnosis and treatment of patients with statin-related muscle complaints, which is central to obtaining the cardiovascular risk reduction from lipid-lowering drugs.

Description:

The goal of the first study will be to generate hypothesis regarding the long-term effects of statin in muscles by studying 7T MRS findings in patients who are currently experiencing statin-related muscle complaints or who have a history of severe reactions to statins (i.e. rhabdomyolysis, anti-HMGCR-associated autoimmune myopathy, or CK elevation > 10 times the upper limit of normal). We anticipate enrolling roughly 5 such patients. The protocol involves a single visit for a blood draw and MRS of calf muscle. The data will be compared to historical controls provided by the Advanced Imaging Research Center.

Second, we will study the effect of short-term statin administration in 5 patients with a history of statin related muscle complaints and 5 controls with no statin related muscle complaints . Controls will be matched for age, weight, and body mass index. Patients will undergo a wash-out of lipid lowering drugs followed by a challenge with simvastatin 40 mg daily (similar to a statin withdrawal and rechallenge). We chose simvastatin since it is the most common statin that caused myopathy according to our preliminary data (as well as most other published reports). Each patient will have 5 visits. The screening visit will involve a review of inclusion/exclusion criteria, blood draw, questionnaire, and instructions to withhold all lipid lowering drugs until visit 1. Any patient with known antibodies to HMGCR will be excluded from the remainder of the study.

Visit 1 will occur 2 weeks after stopping all lipid lowering drugs. A minimum 2 week period off lipid lowering drugs is required to allow clearance of any medication from the systemic circulation. Patients will undergo MRS of the calf muscle and a blood draw. Patients will then start simvastatin 40 mg daily.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 23, 2021
• Est. primary completion date: February 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

Patients who drink large quantities of grapefruit juice (>1 quart daily)

Related Conditions & MeSH terms

• Muscle Aches
• Muscle Cramp
• Muscle Stiffness
• Muscle Weakness
• Myalgia
• Spasm
• Statin-related Muscle Pain

Intervention

Drug:
• Simvastatin
Simvastatin 40 mg daily.

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas

Sponsors (4)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Abhimanyu Garg, Jimin Ren, Prishant Mishra

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pre- and Post-phosphocreatine Relaxation Time	Measure differences in pre- and post-phosphocreatine relaxation time in SAMS (Statin Associated Muscle Symptoms) patients on simvastatin compared to placebo.	Baseline, 10 Weeks