Double-blind crossover trial of trimethoprim-sulfamethoxazole in spinocerebellar ataxia type 3/Machado-Joseph disease

Objective: To evaluate the efficiency of a combination of trimethoprim and sulfamethoxazole in patients with spinocerebellar ataxia type 3/Machado-Jos eph disease (SCA3/MJD). Design: Placebo-controlled, double-blind crossover trial in 22 patients wit h genetically confirmed SCA3/MJD. Study phases of 6 months were separated b y a washout period of 4 weeks. Dosages were a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim, 80 mg, and sulfamethoxazole, 400 mg, twice d aily for 5.5 months. Setting: Outpatient department of the Neurological Clinic, Ruhr-University, Bochum, Germany. Main Outcome Measures: Ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing. Effects on the vis ual system were studied using the achromatic Vision Contrast Test System an d the Farnsworth-Munsell 100-hue test for color discrimination. Physical an d mental health were documented using the Medical Outcomes Study 36-Item Sh ort-Form Health Survey. Subgroup analyses assessed the influence of age, se x, age at onset, duration of the disease, phenotype, and CAG repeat length on test performance. Results: Twenty of 22 patients completed the study. Dropouts were due to a rash (placebo phase) and an attempted suicide in a family conflict. Trimeth oprim-sulfamethoxazole therapy had no significant effect in SCA3/MJD patien ts in the short-term analysis (2 weeks) or in the long-term interval (6 mon ths). Conclusions: In contrast to previous reports that studied smaller groups of patients, treatment with trimethoprim-sulfamethoxazole did not improve the diverse and complex movement disorders caused by SCA3/MJD. Trimethoprim-su lfamethoxazole had no effect on the visual system and cannot be recommended as a continuous treatment for SCA3/MJD patients.