Buspirone Treatment of Iatrogenic Dyskinesias in Advanced Parkinson' Disease (BUSPARK)

Assistance Publique - Hôpitaux de Paris

Status and phase

Completed

Phase 3

Conditions

Parkinson

Treatments

Drug: Placebo

Drug: Buspirone

Study type

Interventional

Funder types

Other

Identifiers

NCT02617017

2015-002332-41 (EudraCT Number)

P130909

Details and patient eligibility

About

Parkinson's disease (PD) is one of the most common neurodegenerative diseases, with a higher prevalence in the elderly. Levodopa induced dyskinesias (LID) are a major motor complications that impair quality of life for patients with PD. The mechanisms of these dyskinesias remain unclear, but several hypotheses have been put forward: non continuous, pulsatile stimulation of dopaminergic receptors, or alterations of other neurotransmitters within the motor striatum such as glutamate and serotonin.

Few strategies are now available to treat severe LID:

Medications: reduction of dopaminergic treatment, addition of amantadine,
Functional neurosurgery. The purpose of this study is to investigate the efficacy of buspirone in PD patients suffering from dyskinesias. The role of serotonin in the occurrence of LID was recently demonstrated in transplant PD patients and a test double-blind, single dose was achieved. Following administration of 10 mg oral buspirone, a 5HT1A agonist, LID were clearly improved. A antidyskinetic effect of buspirone had already been reported in 1991 and 1994, but identification of buspirone as a serotonin receptor agonist has been reported more recently.

This trial is aimed at (1) validate the serotoninergic hypothesis of hyperkinetic levodopa induced dyskinesias (LID) in Pakinson's disease patients, (2) evaluate, in a phase 3 trial, the motor efficacy of buspirone to improve LID vs placebo, (3) look at a possible dose/effect relationship and (4) check the hypothesis of a better therapeutic ratio using the association of buspirone and amantadine instead than a single drug.

Enrollment

99 patients

Sex

All

Ages

35 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

The subject is an out-patient between 35 year and 80 years of age
Diagnosis of idiopathic Parkinson's disease according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria
Dyskinesias are present more than 25% of the waking day according to item 4-1 of MDS-UPDRS
Dyskinesias are at least moderately disabling item 4-2 of MDS-UPDRS replaced by Dyskinesias are at least slightly disabling item 4-2 of MDS-UPDRS (amendment n°2)
The subject is able to identify dyskinesia, ON and OFF, and apply to his/her own state
Stable dose of anti-Parkinsonian drugs for at least 4 weeks up to the screening
The subject is considered as being optimally treated at the time of inclusion
Written and signed informed consent to participate in the study
Maximal Hoehn and Yahr staging : III in "ON" phases, IV in "OFF"
Active affiliation to social security
Menopausal or under contraception for woman

Exclusion Criteria

Female subjects : pregnant or lactating
Atypical parkinsonian syndrome
Weight less than 40 Kgs
Mini-Mental State Examination (MMSE) less than 24
The subject is participating in another clinical study within the past 12 weeks
Planned participation in another therapeutic clinical study
Previous treatment with buspirone, less than 6 months before Week 0
Known allergy to buspirone
Known lactose intolerance
Clinically significant illness that might interfere with the study
Dementia or other psychiatric illness
Drug or alcohol abuse replaced by Substance use disorder (alcohol i.e. > 3 drinks per day for men and > 2 drinks per day for women,drug, medicinal product) (amendment n°1)
Legal incapacity or limited legal capacity
Deep brain stimulation performed less than 12 months before protocol initiation, or unstable parameters of stimulation 4 weeks before week 0
Severe renal and / or hepatic impairment
History of seizures or epilepsy