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7 Tesla MRI Study in Patients With Statin Related Muscle Complaints

Primary Purpose

Statin-related Muscle Pain, Muscle Aches, Muscle Weakness

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Statin-related Muscle Pain

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Arm 1 (Observational Arm)

Arm 2 (Interventional Experimental Arm)

Arm 3 (Interventional Control Arm)

Arm Description

Patients in substudy 1 will be identified by the PI from the clinic as individuals who are currently experiencing statin related muscle complaints or who have had severe reactions to statins in the past. There is going to be only one visit which will last for apprximately 3.5 hrs. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS.

Subjects with statin related muscle complaints were enrolled in this arm and will have 3 visits. First visit is screening visit which will last for about 2 hrs and the next 2 visits will last for about 3.5 hrs. The screening visit will occur 2 weeks prior to visit 1. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS. Some volunteers who do/do not regularly exercise or are/are not active in sports may be asked to exercise prior to the MRS. This exercise may be in the form of hand grasps, toe-raises, bicycling on a stationary bike or walking on a treadmill. Exercise will be limited to up to one hour, during which time the subject's vital signs and blood oxygenation will be monitored. During the scan, the subject's heart rate and respiratory rate may be monitored

Subjects with no statin related muscle complaints were enrolled in this arm and will have 3 visits. First visit is screening visit which will last for about 2 hrs and the next 2 visits will last for about 3.5 hrs. The screening visit will occur 2 weeks prior to visit 1. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS. Some volunteers who do/do not regularly exercise or are/are not active in sports may be asked to exercise prior to the MRS. This exercise may be in the form of hand grasps, toe-raises, bicycling on a stationary bike or walking on a treadmill. Exercise will be limited to up to one hour, during which time the subject's vital signs and blood oxygenation will be monitored. During the scan, the subject's heart rate and respiratory rate may be monitored

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
May 15, 2020
Last Updated
April 5, 2022
Sponsor
University of Texas Southwestern Medical Center
Collaborators
Abhimanyu Garg, Prishant Mishra, Jimin Ren
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1. Study Identification

Unique Protocol Identification Number
NCT04575090
Brief Title
7 Tesla MRI Study in Patients With Statin Related Muscle Complaints
Official Title
7 Tesla MRI Study in Patients With Statin Related Muscle Complaints
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 5, 2016 (Actual)
Primary Completion Date
February 20, 2017 (Actual)
Study Completion Date
June 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Texas Southwestern Medical Center
Collaborators
Abhimanyu Garg, Prishant Mishra, Jimin Ren

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Statin-related Muscle Pain, Muscle Aches, Muscle Weakness, Muscle Cramp, Muscle Stiffness

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (Observational Arm)
Arm Type
No Intervention
Arm Description
Patients in substudy 1 will be identified by the PI from the clinic as individuals who are currently experiencing statin related muscle complaints or who have had severe reactions to statins in the past. There is going to be only one visit which will last for apprximately 3.5 hrs. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS.
Arm Title
Arm 2 (Interventional Experimental Arm)
Arm Type
Experimental
Arm Description
Subjects with statin related muscle complaints were enrolled in this arm and will have 3 visits. First visit is screening visit which will last for about 2 hrs and the next 2 visits will last for about 3.5 hrs. The screening visit will occur 2 weeks prior to visit 1. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS. Some volunteers who do/do not regularly exercise or are/are not active in sports may be asked to exercise prior to the MRS. This exercise may be in the form of hand grasps, toe-raises, bicycling on a stationary bike or walking on a treadmill. Exercise will be limited to up to one hour, during which time the subject's vital signs and blood oxygenation will be monitored. During the scan, the subject's heart rate and respiratory rate may be monitored
Arm Title
Arm 3 (Interventional Control Arm)
Arm Type
Experimental
Arm Description
Subjects with no statin related muscle complaints were enrolled in this arm and will have 3 visits. First visit is screening visit which will last for about 2 hrs and the next 2 visits will last for about 3.5 hrs. The screening visit will occur 2 weeks prior to visit 1. Subjects will have height, weight and vitals measured. They will be asked pain and and demographic questionnaire. They will have their blood draw and will undergo MRS. Some volunteers who do/do not regularly exercise or are/are not active in sports may be asked to exercise prior to the MRS. This exercise may be in the form of hand grasps, toe-raises, bicycling on a stationary bike or walking on a treadmill. Exercise will be limited to up to one hour, during which time the subject's vital signs and blood oxygenation will be monitored. During the scan, the subject's heart rate and respiratory rate may be monitored
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
Simvastatin 40 mg daily.
Primary Outcome Measure Information:
Title
Change in Pre- and Post-phosphocreatine Relaxation Time
Description
Measure differences in pre- and post-phosphocreatine relaxation time in SAMS (Statin Associated Muscle Symptoms) patients on simvastatin compared to placebo.
Time Frame
Baseline, 10 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Facility Information:
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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7 Tesla MRI Study in Patients With Statin Related Muscle Complaints

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