Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.
Condition(s) studied
Investigational drug(s) / intervention(s)
Assessment of severity of ICD (impulse control disorders): Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) administered at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of motor and non-motors symptoms of PD Evaluation of hyper- and hypodopaminergic behaviors: Hyper- and hypodopaminergic behaviors (Ardouin's scale); Movement disorders society sponsored unified Parkinson's disease rating scale (MDS-UPDR), and daytime and night time sleep by scale for outcomes in Parkinson's disease SLEEP (SCOPA-SLEEP, ISI, PDSS-2) administered at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of quality of life: Parkinson's Disease questionnaire (PDQ-39) administered at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of depression: Montgomery-Åsberg Depression Rating Scale (MADRS) administered at day 0 and day 56 (week 8)
Assessment of cognition: Cognitive state of patients by Montreal Cognitive Assessment (MOCA) assessed at day 0
Assessment of severity of Parkinson Disease: Clinical Global Impression Severity scale (CGIS) administered at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)
Cardiac monitoring: Electrocardiogram realized at day 0, 28 and 56.
Study summary
There is no consensus on the treatment of Impulse Control Disorder (ICD) in Parkinson Disease (PD) though it is recommended to reduce the dosage of dopamine agonists (DA).
Reduction of DA frequently leads to a worsening of motor signs (parkinsonism or dyskinesias due to the concomitant increase of levodopa doses) and non-motor signs with the appearance of a DA withdrawal syndrome (DAWS).
Chronic stimulation of the sub-thalamic nuclei may reduce ICD but is restricted to a minority of patients and cases of new-onset ICD symptoms post stimulation have been reported. The benefit of amantadine in pathological gambling is controversial and the efficacy of clozapine has been reported in a few cases but with serious safety limitations. Very recently, naltrexone did not significantly improve ICD.
Thus, an efficacious and safe treatment of ICD in PD remains an unmet need for clinical practice.
Recently, it has been reported that pimavanserin, a selective serotonin 5-HT2A inverse agonist with a satisfactory safety profile without motor side effects, was efficient in improving psychosis, insomnia and day-time sleep in PD.
Pimavanserin, marketed under the tradename NUPLAZID® was approved in 2016 by the U.S. Food and Drug Administration (FDA) for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.
The link between serotonin and ICD has been well established, since the enhancement of 5HT2A receptors stimulation is associated to ICD, since serotonin modulates mesolimbic dopaminergic reward system transmission and given that serotonin neurotransmission is increased during chronic intake of dopamine agonist such as pramipexole which is well-known to induce ICD in PD patients. Thus, there is a large body of evidence suggesting that the decrease of the 5HT2A activity could be efficient in reducing ICD in PD. This further supports the concept of testing the efficacy of pimavanserin (a selective 5HT2A inverse agonist) for treating ICD in PD. Our aim is to conduct a study evaluating the efficacy and safety of pimavanserin on ICD in PD.
Eligibility
Primary outcome measure(s)
- Change in ICD (Impulsive Control Disorders) severity after 8 weeks of treatment evaluated by QUestionnaire for Impulse-compulsive disorder in Parkinson's disease Rating Scale (QUIP-RS). — at day 0 and week 8
The primary endpoint of this study will be assessed in both arms using the total form of QUIP-RS. QUIP-RS has 4 primary questions (pertaining to commonly reported thoughts, urges/desires, and behaviors associated with ICDs), each applied to the 4 ICDs (compulsive gambling, buying, eating, and sexual behavior) and 3 related disorders (medication use, punding, and hobbyism). It uses a 5-point Likert scale (score 0-4 for each question) to gauge the frequency of behaviors. Scores for each ICD and related disorder range from 0 to 16 and the total QUIP-RS score for all ICDs and related disorders combined ranges from 0 to 112, with a higher score indicating greater severity (ie, frequency) of symptoms.
Trial sites (16)
| Facility | City | Region | Status |
|---|---|---|---|
| Service de Neurologie et Centre d'Investigation Clinique CHRU de Besançon, | Besançon | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson (centre coordinateur interrégional pour la région Sud-Est) Service de neurologie C Hôpitaux Universitaires de Lyon Hôpital Neurologique Pierre Wertheimer | Bron | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson (région Sud-Est) Hôpitaux Universitaires de Clermont-Ferrand Hôpital Gabriel Montpied | Clermont-Ferrand | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (région Ile-de-France) Hôpital Henri Mondor | Créteil | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (région Sud-Est) CHU de Grenoble Alpes | Grenoble | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson (centre de coordination pour la région Nord-Ouest) Hôpitaux Universitaires de Lille Hôpital Roger Salengro | Lille | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (région Sud-Ouest) Hôpitaux Universitaires de Limoges | Limoges | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson (centre de coordination pour la région Sud Méditerranée) Hôpitaux Universitaires de Marseille Hôpital La Timone | Marseille | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (centre de coordination pour la région Ouest) Centre d'investigation clinique Hôpitaux Universitaires de Nantes | Nantes | France | |
| SERVICE DE NEUROLOGIE Centre expert Parkinson (centre de coordination pour la région Ile-de-France) Hôpital de la Pitié-Salpêtrière | Paris | France | |
| CIC Hôpitaux Universitaires de Poitiers | Poitiers | France | |
| Service de neurologie, Hôpitaux Universitaires de REIMS | Reims | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (région Ouest) Hôpitaux Universitaires de Rennes-Hôpital Pontchaillou | Rennes | France | |
| SERVICE DE NEUROLOGIE Pathologies du mouvement Centre expert Parkinson (région Nord-Ouest) Hôpitaux Universitaires de Rouen Hôpital Charles Nicolle | Rouen | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson (centre de coordination pour la région Est) Hôpitaux Universitaires de Strasbourg Hôpital de Hautepierre | Strasbourg | France | |
| SERVICE DE NEUROLOGIE Unité Mouvement anormaux Centre expert Parkinson/Centre d'Investigation Clinique -Hôpital Pierre-Paul Riquet | Toulouse | France |
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT06754553 on ClinicalTrials.gov ↗ ← All trials in France