Buspirone Treatment of Iatrogenic Dyskinesias in Advanced Parkinson' Disease
Status:
Unknown status
Trial end date:
2018-06-01
Target enrollment:
Participant gender:
Summary
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.