Placebo controlled, randomised, double blind study of the effects of botulinum A toxin on detrusor sphincter dyssynergia in multiple sclerosis patients
- 1Service de Médecine Physique et Réadaptation, Centre Hospitalier Universitaire, Rennes, France
- 2Centre d’Investigation Clinique INSERM 0203, Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire et Université de Rennes 1, Rennes, France
- 3Service de Rééducation Neurologique et d’Explorations Périnéales, Hôpital Rothschild, Paris, France
- 4Centre de Médecine Physique et Réadaptation Notre Dame de Lourdes, Rennes, France
- 5Service de Médecine Physique et Réadaptation, Centre Hospitalier Universitaire, Bordeaux, France
- Correspondence to: Professor Eric Bellissant Centre d’Investigation Clinique INSERM 0203, Unité de Pharmacologie Clinique, Centre Hospitalier Universitaire de Rennes et Université de Rennes 1, Hôpital de Pontchaillou, 2 rue Henri Le Guilloux, 35033 Rennes cedex, France;
- Received 17 May 2004
- Accepted 1 March 2005
- Revised 6 January 2005
Objective: The purpose of the study was to evaluate the efficacy and safety of botulinum A toxin in the treatment of detrusor sphincter dyssynergia in multiple sclerosis patients.
Methods: This was a multicentre, placebo controlled, randomised, double blind study. Patients with chronic urinary retention were included if they had post-voiding residual urine volume between 100 and 500 ml. They received a single transperineal injection of either botulinum A toxin (100 U Allergan) or placebo in the sphincter and also 5 mg slow release alfuzosin bid over 4 months. Main endpoint was post-voiding residual urine volume assessed 1 month after injection. Follow up duration was 4 months. Statistical analysis was performed using a sequential method, the triangular test.
Results: The study was stopped after the fourth analysis (86 patients had been included: placebo: 41, botulinum A toxin: 45). At inclusion, there was no significant difference between groups whichever variable was considered. Mean (standard deviation) post-voiding residual urine volume was 217 (96) and 220 (99) ml in placebo and botulinum A toxin groups, respectively. One month later, post-voiding residual urine volume was 206 (145) and 186 (158) ml (p = 0.45) in placebo and botulinum A toxin groups, respectively. However, compared to placebo, botulinum A toxin significantly increased voiding volume (+54%, p = 0.02) and reduced pre-micturition (−29%, p = 0.02) and maximal (−21%, p = 0.02) detrusor pressures. Other secondary urodynamic endpoints and tolerance were similar in the two groups.
Conclusions: In multiple sclerosis patients with detrusor sphincter dyssynergia, a single injection of botulinum A toxin (100 U Allergan) does not decrease post-voiding residual urine volume.
- EDSS, Expanded Disability Status Scale
- IPSS, International Prostatism Symptom Score
- SD, standard deviation
This study was supported by the Fondation pour la Recherche Médicale, Paris (France), the Comité de la Recherche Clinique du Centre Hospitalier Universitaire de Rennes, Rennes (France), the Groupe d’Etude de Neuro-Urologie de Langue Française, Paris (France), and the Association pour la Recherche dans la Sclérose en Plaques, Paris (France). None of the above mentioned funding organisation participated in the design, conduct, interpretation, or analysis of the study or review or approval of the manuscript.
Competing interests: none declared
Study organisation: study chairmen: Philippe Gallien (principal investigator) and Eric Bellissant (methodologist); monitor: Jean-Michel Reymann; sequential statistical analysis: Véronique Sébille; data management and standard statistical analysis: Habiba Mesbah; quality assurance: Marie-Françoise Mordelet; clinical research assistant: Christelle Tual.
In addition to the authors, study investigators and institutions were as follows: M-P Dorval, Service de Médecine Physique et Réadaptation, Centre Hospitalier Universitaire, Brest, France and P Brunel, Service de Médecine Physique et Réadaptation C3RF, Centre Hospitalier Universitaire, Angers, France.