7 Tesla MRI Study in Patients With Statin Related Muscle Complaints
Condition: Statin-related Muscle Pain; Muscle Aches; Muscle Weakness; Muscle Cramp; Muscle Stiffness
MeSH terms: Muscle Weakness; Myalgia; Muscle Cramp; Spasm
Study type: Interventional

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.
    

Intervention name(s): Simvastatin
Intervention type(s): Drug
Intervention description(s): Simvastatin 40 mg daily.
Intervention MeSH terms: Simvastatin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic