Related Experiment Videos
A double-blind placebo controlled trial of diltiazem in Duchenne dystrophy
W Pernice1, R Beckmann, U P Ketelsen
1Abteilung Pädiatrische Muskelerkrankungen, Universitäts-Kinderklinik, Freiburg.
Abstract:
The role of calcium accumulation in the pathogenesis of Duchenne muscular dystrophy (DMD) has already been discussed. Several trials with different calcium-blocking drugs have revealed no clinical benefit. In addition, the present study includes histological investigations and computer tomography to verify therapeutic effects. In a randomized placebo-controlled double-blind study, 13 DMD patients aged from 3-10 years (mean, 7 years) were treated with 5 mg/kg diltiazem daily for 1 year. Compared with before therapy, the number of calcium-positive muscular fibres was remarkably reduced in the treated DMD patients, but not in the placebo group. The evaluation of all other biochemical and clinical parameters revealed no significant effects of the diltiazem therapy. The muscular X-ray density measured by computer tomography decreased under treatment. After the evaluation of the double-blind study, the code was broken. Therapy, however, was continued in the treated group and started in the placebo group. After 3 years of diltiazem therapy the clinical status of all 26 patients of the study and 20 additional DMD patients who were treated with diltiazem was compared with 46 untreated DMD patients of the same age and stage in our department. No obvious clinical benefit of diltiazem therapy could be observed.
Insights
Diltiazem therapy reduced calcium in muscle fibers for Duchenne muscular dystrophy (DMD) patients, but did not improve clinical outcomes or slow disease progression over three years.
Area of Science:
- Biomedical Research
- Neuromuscular Disorders
- Pharmacology
Background:
- Calcium accumulation is implicated in Duchenne muscular dystrophy (DMD) pathogenesis.
- Previous trials with calcium channel blockers in DMD have shown no clinical benefit.
Purpose of the Study:
- To investigate the therapeutic effects of diltiazem on calcium accumulation in DMD patients.
- To assess the clinical efficacy of diltiazem in DMD over short and long-term treatment periods.
Main Methods:
- A randomized, placebo-controlled, double-blind study involving 13 DMD patients treated with diltiazem for 1 year.
- Histological investigations and computer tomography (CT) were used to evaluate therapeutic effects.
- Long-term follow-up assessed clinical status after 3 years of diltiazem therapy in a larger cohort.
Main Results:
- Diltiazem treatment significantly reduced the number of calcium-positive muscle fibers in DMD patients compared to placebo.
- No significant improvements were observed in other biochemical or clinical parameters during the 1-year trial.
- Muscular X-ray density, measured by CT, decreased with diltiazem treatment.
- No obvious clinical benefit was observed after 3 years of diltiazem therapy in all treated DMD patients.
Conclusions:
- While diltiazem can reduce calcium accumulation in muscle fibers of DMD patients, it does not translate to clinical benefit.
- Diltiazem therapy does not appear to slow disease progression or improve the clinical status of DMD patients in the long term.