Study of Pimavanserin Efficacy for the Treatment of Impulse Control Disorders in Parkinson's Disease

Who is this study for? Patients with Parkinson Disease
What treatments are being studied? Pimavanserin
Status: Recruiting
Location: See all (16) locations...
Intervention Type: Drug, Procedure, Behavioral
Study Type: Interventional
Study Phase: Phase 2
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. This clinical trial is conducted with the support of the French NS-Park/FCRIN (French Clinical Research Infrastructure Network) network.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 35
Maximum Age: 75
Healthy Volunteers: No
View:

• Patient with PD according to the UKPDSBB criteria for at least 1 year before randomization

• Patient, man or woman, aged from 35 to 75 years old

• Patient with moderately severe ICD assessed by QUIP-RS (each item being rated 0-16) defined as:

• a combined ICD total score (defined as the sum of the 4 ICD sub-scores (pathological gambling + buying + hypersexuality + eating)) superior or equal to 10 or,

• at least one of the 4 ICD sub-scores in the following range:

• pathological gambling sub-score from 6 to 12 (included),

• buying sub-score from 8 to 12 (included),

• hypersexuality sub-score from 8 to 12 (included),

• eating sub-score from 7 to 12 (included) (Weintraub et al., 2012). The use of lower margins will guarantee that the patient experiences behavioral disturbances severe enough to justify pimavanserin treatment. On the other hand, the use of upper margins will guarantee that the patients included in the trial will not suffer from ICD severe enough to question ethically the use of placebo during the 8 weeks of the treatment. Eligibility of patients with QUIP-RS sub-scores above 12 will be assessed upon investigator's request by an adjudication committee composed by independent experts external to the study (cf IX.3 Adjudication Committee).

• ICD onset after PD onset and after initiation of dopaminergic drugs

• Patient treated by dopaminergic drugs for at least 3 months before randomization

• Patient treated with a stable regimen of levodopa, dopamine agonists, COMT and MAOB inhibitors, amantadine, anticholinergic, antidepressant and benzodiazepine for at least 1 month before the randomization and be willing to remain on the same doses throughout the course of their participation in the trial (Papay et al., 2014)

• Patient with health insurance

• Patient/ guardian / curator who sign the written informed consent

• For women of childbearing potential, use of an effective contraception method* for at least 1 month prior to randomization until 8 weeks after the last dose of study drug administration. Women who do not have an effective contraception* must : have had her last natural menstruation ≥24 months prior to the selection visit, or have been surgically sterilized prior to the selection visit, or have had a hysterectomy prior to the selection visit.

Locations
Other Locations
France
Service de Neurologie -CHU Besançon
Recruiting
Besançon
SERVICE DE NEUROLOGIE C, Unité mouvement anormaux/Centre expert Parkinson, CHU de Lyon, Hopital neurologique Pierre Wertheimer
Recruiting
Bron
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU Clermont-Ferrand, Hopital Gabriel Montpied
Recruiting
Clermont-ferrand
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, Hopital Henri Mondor
Recruiting
Créteil
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Grenoble Alpes
Recruiting
Grenoble
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, CHU de Lille, Hopital Roger Salengro
Recruiting
Lille
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Limoges
Recruiting
Limoges
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, Hopital de la Timone
Recruiting
Marseille
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Nantes, Hopital Laennec
Recruiting
Nantes
SERVICE DE NEUROLOGIE Centre Expert Parkinson Hopital de la Pitié-Salpêtrière
Recruiting
Paris
Centre d'Inverstigation Clinique, CHU de Poitiers
Recruiting
Poitiers
SERVICE DE NEUROLOGIE, CHU de REIMS
Recruiting
Reims
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rennes, Hopital Pontchaillou
Recruiting
Rennes
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rouen, Hopital Charles Nicolle
Recruiting
Rouen
SERVICE DE NEUROLOGIE Unité de Mouvements Anormaux/Centre expert Parkinson, CHU de Strasbourg, Hopital de Hautepierre
Recruiting
Strasbourg
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Toulouse, Hopital Pierre-Paul Riquet
Recruiting
Toulouse
Contact Information
Primary
Mathieu ANHEIM, MD
mathieu.anheim@chru-strasbourg.fr
+33 3 88 12 85 35
Backup
Olivier RASCOL, MD
olivier.rascol@univ-tlse3.fr
+33 5 61 14 59 62
Time Frame
Start Date: October 23, 2020
Estimated Completion Date: July 31, 2023
Participants
Target number of participants: 130
Treatments
Experimental: PIMAVANSERIN
In this arm, each patient will take orally, once daily 2 tablets of active drug pimavanserin of 17mg each and this during the 8-weeks treatment period.
Placebo Comparator: PLACEBO
In this arm, each patient will take orally, once daily, 2 tablets of matching placebo (containing all of the same excipients except for the active compound) and this during the 8-weeks treatment period.
Sponsors
Collaborators: F-CRIN, NS-PARK, EUCLID Clinical Trial Platform
Leads: University Hospital, Strasbourg, France

This content was sourced from clinicaltrials.gov

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