Statins Induced Myopathy
Conditions
Brief summary
Statins are one of the most efficient drugs for the treatment of hypercholesterolemia which is considered as one of the main risk factors for atherosclerosis., and therefore they are frequently prescribed medications \[1-2\]. However, statins therapy is associated with myotoxicity. This effect of different severity ranges forms myopathy, myalgia, myositis, and rhabdomyolysis \[3\]. Different studies set a number of hypotheses to explain the pathophysiological events of statin-induced myopathy. These hypotheses include disturbance of mitochondrial function resulting in cytoplasmic Ca2+ overload as well as decreased level of the potent antioxidant and membrane stabilizer coenzyme Q10/ubiquinone \[4-5\] This study tries to introduce a complementary therapy that targets these molecular events. This therapeutic protocol includes dantrolene the muscle relaxant that acts as a ryanodine receptor (RYR) antagonist and thus decreases Ca release in cytoplasm.
Interventions
DRUGDantrolene
Dantrolene sodium capsule 25 mg orally once daily for 4 weeks. Dose may be titrated to 50 mg daily after 1 week if tolerated. Used to assess impact on muscle pain and biomarkers of muscle injury in patients with statin-induced myopathy.
DRUGPlacebo
Oral placebo capsule matching dantrolene in size and appearance, administered once daily for 4 weeks.
Sponsors
Tanta University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Participants will be randomized to receive either dantrolene or placebo for 4 weeks.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Adults aged 18-75 years Currently receiving statin therapy for at least 4 weeks Clinical symptoms suggestive of statin-induced myopathy (e.g., muscle pain, weakness) Elevated serum creatine kinase (CK) ≥1.5x upper limit of normal Able and willing to provide informed consent Willing to discontinue statins during the study period (if protocol requires)
Exclusion criteria
Known hypersensitivity to dantrolene History of severe liver disease or abnormal liver function tests (ALT or AST \> 2x ULN) Use of interacting drugs that may increase dantrolene toxicity (e.g., calcium channel blockers like verapamil) Renal impairment (e.g., serum creatinine \>2.0 mg/dL) Diagnosed neuromuscular disorders unrelated to statins (e.g., ALS, muscular dystrophy) Pregnant or breastfeeding women Participation in another clinical trial within the past 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Creatine Kinase (CK) Level | Baseline and 4 weeks after intervention start | Evaluation of the effect of dantrolene on serum creatine kinase, a biomarker of muscle injury, in statin-induced myopathy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Muscle Pain Score (Visual Analog Scale) | Baseline and Week 4 | Assessment of self-reported muscle pain severity using a 10-point VAS. Time Frame: Baseline and Week 4 |
| Change in Serum Lactate Dehydrogenase (LDH) Level | Baseline and Week 4 | LDH as an additional marker of muscle damage. |
| Number of Participants With Adverse Effects Related to Dantrolene | Throughout the 4-week intervention period | Safety evaluation of dantrolene use over the study period. |
Outcome results
None listed