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A double-blind placebo controlled trial of diltiazem in duchenne dystrophy

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Summary

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 muscularX-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.

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Abbreviations

ALD:

Aldolase

Ca:

Calcium

CK:

Creatine kinase

CKMB:

Creatine kinase MB

GOT:

Glutamic-oxaloacetic transaminase

GPT:

Glutamic-pyruvic transaminase

LDH:

Lactate dehydrogenase

Mg:

Magnesium

References

  1. Anand R, Emery AE (1982) Verapamil in calcium-stimulated enzyme efflux from skeletal muscle. Clin Chem 28:1482–1484

    CAS  PubMed  Google Scholar 

  2. Beckmann R (1983) Muskeldystrophie (Duchenne) — Probleme der Erfassung und Therapie. Wiss. Zeitschr. der Friedrich-Schiller-Univ. Jena. III. Jenaer Myologic-Colloquinm 4/5

  3. Bertorini BE, Cornelio F, Bhattacharya SK, Palmieri GMA, Dones I, Dworzak F, Branbati B (1984) Calcium and magnesium content in fetuses at risk and prenecrotic Duchenne muscular dystrophy. Neurology 3:1436–1443

    Article  Google Scholar 

  4. Bertorini TE, Brown R, Griffin J, Hinon AB, Igarashi M, Karas J, McGee JE, Palmieri GMA (1986) Attempts to correct muscle calcium accumulation in Duchenne muscular dystrophy (DMD). Muscle Nerve 9 [5S]:201

    Google Scholar 

  5. Bhattacharya SK, Palmieri GMA, Bertorini TE, Nütting DF (1982) The effects of Diltiazem in dystrophic hamsters. Muscle Nerve 5:73–78

    Article  CAS  PubMed  Google Scholar 

  6. Bodensteiner JB, Engel AG (1978) Intracellular calcium accumulation in Duchenne dystrophy and other myopathies. A study of 5670 muscle fibres in 114 biopsies. Neurology 28:439–446

    Article  CAS  PubMed  Google Scholar 

  7. Brooke MH, Fenichel GM, Griggs RC, Mendell RJ, Moxley R, Miller JP, Province MA, CIDD Group (1983) Clinical investigation in Duchenne muscular dystrophy: II Determination of the “power” of therapeutical trials based on the natural history. Muscle Nerve 6:91–103

    Article  CAS  PubMed  Google Scholar 

  8. Brooke MH, Fenichel GM, Griggs RC, Mendell J, Miller JP, Moxley R (1984) A trial of nifedipine in Duchenne muscular dystrophy. Neurology 34:290

    Google Scholar 

  9. Cornelio F, Dworzak F, Morandi L (1984) Therapeutic trials in Duchenne muscular dystrophy. Evaluation of the patients: proposal for a protocol. Ital J Neurol Sci 5 [Suppl 1]:133–136

    Google Scholar 

  10. Davies KE, Forrest S, Smith T, Kenwrick S, Ball S, Dorkins H, Patterson M (1987) Molecular analysis of human muscular dystrophies. Muscle Nerve 10:191–199

    Article  CAS  PubMed  Google Scholar 

  11. Den Dunnen JT, Backer E, Klein-Breterler EG, Pearson PL, Van Ommen GJB (1987) Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels. Nature 329:640–642

    Article  Google Scholar 

  12. Dick DJ, Gardner-Medwin D, Gates PG, Gipson M, Simpson JM, Walls TJ (1986) A trial of fluranizidine in the treatment of Duchenne muscular dystrophy. Muscle Nerve 5:73–78

    Google Scholar 

  13. Emery AEH, Burt T (1980) Intracellular calcium and pathogenesis and antenatal diagnosis of Duchenne muscular dystrophy. Br Med J 280:355–357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Emery AEH, Skinner R (1983) Double-blind controlled trial of a “calcium blocker” in Duchenne muscular dystrophy. Cadiomyology 2(1–2):13–23

    Google Scholar 

  15. Hoffmann EP, Knudson CM, Campbell KP, Kunkel LM (1987) Subcellular fractionation of dystrophin to the triads of skeletal muscle. Nature 330:754–757

    Article  Google Scholar 

  16. Ketelsen U-P (1984) Duchenne Muskeldystrophie. Ein Beitrag zur Pathogenese der Muskelzellnekrose in frühen Krankheitsstadien und bei männlichen Föten definitiver Überträgerinnen. Therapiewoche 34:3495–3507

    Google Scholar 

  17. Lossnitzer K, Janke J, Hein B, Stauch M, Fleckenstein A (1975) Disturbed myocardial calcium metabolism: a possible pathogenetic factor in the hereditary cardiomyopathy of the syrian hamster. In: Fleckenstein A, Rona G (eds) Recent advances in studies on cardiac structure and metabolism, vol 6. University Park Press, Baltimore, pp 207–217

    Google Scholar 

  18. Moxley RT, Brooke MH, Fenickel GM, Mendell JR, Griggs RC, Miller JP, Province MA, Patterson V, CIDD Group (1987) Clinical investigation in Duchenne dystrophy: VI Double-blind controlled trial of nifedipine. Muscle Nerve 10:22–33

    Article  PubMed  Google Scholar 

  19. Oberc MA, Engel WK (1977) Ultrastructural localisation of calcium in normal and abnormal skeletal muscle. Lab Invest 36:366–577

    Google Scholar 

  20. Pearse AGE (1972) Histochemistry: theoretical and applied, 3d edn. Edinburgh, Churchill Livingstone, pp 1137–1138

    Google Scholar 

  21. Pernice W, Guggolz MA, Guggolz M, Beckmann R, Wais U (1986) A mathematical analysis of creatine kinase activity in the course of Duchenne muscular dystrophy. Muscle Nerve 9:333–340

    Article  CAS  PubMed  Google Scholar 

  22. Wrogemann K, Pena SDJ (1976) Mitochondrial calcium overload: a general mechanism for cell necrosis in muscle diseases. Lancet I:672–673

    Article  Google Scholar 

  23. Yarom R, Meyer S, More R, Liebergal M, Eldor A (1983) Platelet abnormalities in muscular dystrophy. Thromb Hemost 49:168–172

    CAS  Google Scholar 

  24. Yoshida M, Ando K, Stoyoshi E (1983) Abnormalities of erythrocytes in Duchenne muscular dystrophy. Ann Neurol 13:649–653

    Article  CAS  PubMed  Google Scholar 

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Pernice, W., Beckmann, R., Ketelsen, UP. et al. A double-blind placebo controlled trial of diltiazem in duchenne dystrophy. Klin Wochenschr 66, 565–570 (1988). https://doi.org/10.1007/BF01720830

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  • DOI: https://doi.org/10.1007/BF01720830

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