Dantrolene in Statin-induced Myopathy

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Statins Induced Myopathy
• Intervention / Treatment: Drug: Dantrolene; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 23
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dantrolene Group; Participants will receive oral dantrolene 25 mg capsule once daily for 4 weeks. Dose may be increased to 50 mg daily based on tolerance and response. Dantrolene is used to evaluate its potential effect on muscle symptoms and biomarkers in statin-induced myopathy.	Drug: Dantrolene; 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.; Other Names: Dantrium, Ryanodex
Placebo Comparator: Placebo Group; Participants will receive a matching oral placebo capsule once daily for 4 weeks, designed to mimic dantrolene in appearance. This arm serves as the control to assess the efficacy and safety of dantrolene in comparison to placebo	Drug: Placebo; Oral placebo capsule matching dantrolene in size and appearance, administered once daily for 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Creatine Kinase (CK) Level	Evaluation of the effect of dantrolene on serum creatine kinase, a biomarker of muscle injury, in statin-induced myopathy.	Baseline and 4 weeks after intervention start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Muscle Pain Score (Visual Analog Scale)	Assessment of self-reported muscle pain severity using a 10-point VAS. Time Frame: Baseline and Week 4	Baseline and Week 4
Change in Serum Lactate Dehydrogenase (LDH) Level	LDH as an additional marker of muscle damage.	Baseline and Week 4
Number of Participants With Adverse Effects Related to Dantrolene	Safety evaluation of dantrolene use over the study period.	Throughout the 4-week intervention period

Collaborators and Investigators

• Sponsor: Tanta University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2027
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: May 4, 2025
• First Submitted That Met QC Criteria: May 4, 2025
• First Posted (Actual): May 13, 2025

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 4, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Diseases; Muscular Diseases; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Muscle Relaxants, Central; Dantrolene
• Other Study ID Numbers: Dan1199

Drug and device information, study documents

• 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