Efficacy and safety of clonidine for the treatment of impulse control disorder in Parkinson's disease: a multicenter, parallel, randomised, double-blind, Phase 2b Clinical trial.
Clonidine
Impulse control disorder
Noradrenergic system
Parkinson’s disease
QUIP-RS
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
received:
04
05
2023
accepted:
06
06
2023
revised:
05
06
2023
medline:
21
9
2023
pubmed:
20
6
2023
entrez:
20
6
2023
Statut:
ppublish
Résumé
Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD). We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs. We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success. Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6). Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted. The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018.
Sections du résumé
BACKGROUND
BACKGROUND
Impulse control disorders (ICDs) are frequently encountered in Parkinson's disease (PD).
OBJECTIVES
OBJECTIVE
We aimed to assess whether clonidine, an α2-adrenergic receptor agonist, would improve ICDs.
METHODS
METHODS
We conducted a multicentre trial in five movement disorder departments. Patients with PD and ICDs (n = 41) were enrolled in an 8-week, randomised (1:1), double-blind, placebo-controlled study of clonidine (75 μg twice a day). Randomisation and allocation to the trial group were carried out by a central computer system. The primary outcome was the change at 8 weeks in symptom severity using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) score. A reduction of the most elevated subscore of the QUIP-RS of more than 3 points without any increase in the other QUIP-RS dimension defined success.
RESULTS
RESULTS
Between 15 May 2019 and 10 September 2021, 19 patients in the clonidine group and 20 patients in the placebo group were enrolled. The proportion difference of success in reducing QUIP-RS at 8 weeks, was 7% (one-sided upper 90% CI 27%) with 42.1% of success in the clonidine group and 35.0% in the placebo group. Compared to patients in the placebo group, patients in the clonidine group experienced a greater reduction in the total QUIP-RS score at 8 weeks (11.0 points vs. 3.6).
DISCUSSION
CONCLUSIONS
Clonidine was well tolerated but our study was not enough powerful to demonstrate significant superiority compared to placebo in reducing ICDs despite a greater reduction of total QUIP score at 8 weeks. A phase 3 study should be conducted.
TRIAL REGISTRATION
BACKGROUND
The study was registered (NCT03552068) on clinicaltrials.gov on June 11, 2018.
Identifiants
pubmed: 37338615
doi: 10.1007/s00415-023-11814-y
pii: 10.1007/s00415-023-11814-y
pmc: PMC10511565
doi:
Substances chimiques
Clonidine
MN3L5RMN02
Banques de données
ClinicalTrials.gov
['NCT03552068']
Types de publication
Randomized Controlled Trial
Multicenter Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4851-4859Subventions
Organisme : Ministère de l'Enseignement Supérieur et de la Recherche
ID : PHRC interrégional
Informations de copyright
© 2023. The Author(s).
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