Randomized Placebo Controlled Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.
NCT ID: NCT03947216
Last Updated: 2025-01-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
117 participants
INTERVENTIONAL
2020-10-23
2024-06-17
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Trial Evaluating the Efficacy of Pimavanserin, a Selective Serotonin 5-HydroxyTryptamine-2A (5HT2A) Inverse Agonist, to Treat Impulse Control Disorders in Parkinson's Disease.
NCT06754553
Safety and Efficacy of Pimavanserin in Adults With Parkinson's Disease and Depression
NCT03482882
A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis
NCT01174004
Study to Evaluate Safety and Daytime Sedation in Subjects With Parkinson's Disease With Neuropsychiatric Symptoms Treated With Pimavanserin or Low-Dose Quetiapine
NCT04164758
Open-Label Study With Pimavanserin on Activities of Daily Living in Subjects With Parkinson's Disease Psychosis
NCT04292223
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
Active drug: pimavanserin 17mg (2 strength tablets)
Pimavanserin 17mg (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Assessment of severity of ICD (impulse control disorders)
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated 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) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of quality of life
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of depression
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)
Assessment of cognition
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.
Assessment of severity of Parkinson Disease
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)
Blood analysis
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56
Cardiac monitoring
Electrocardiogram will be realized at day 0, 28 and 56.
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.
Placebo: 2 tablets containing same excipients except active compound
Placebo (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Assessment of severity of ICD (impulse control disorders)
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated 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) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of quality of life
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of depression
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)
Assessment of cognition
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.
Assessment of severity of Parkinson Disease
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)
Blood analysis
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56
Cardiac monitoring
Electrocardiogram will be realized at day 0, 28 and 56.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Active drug: pimavanserin 17mg (2 strength tablets)
Pimavanserin 17mg (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Placebo: 2 tablets containing same excipients except active compound
Placebo (2 strength tablets) will be taken orally daily from day 1 to Visit 4 (Week 8)
Assessment of severity of ICD (impulse control disorders)
Questionnaire for impulsive-compulsive disorders in Parkinson's disease rating scale (QUIP-RS) will be administrated 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) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of quality of life
Parkinson's Disease questionnaire (PDQ-39) will be administrated at day 0, day 28 (Week 4) and day 56 (Week 8)
Assessment of depression
Montgomery-Åsberg Depression Rating Scale (MADRS) will be administrated at day 0 and day 56 (week 8)
Assessment of cognition
Cognitive state of patients by Montreal Cognitive Assessment (MOCA) will be assessed at day 0.
Assessment of severity of Parkinson Disease
Clinical Global Impression Severity scale (CGIS) will be administrated at day 0 , day 7, day 14, day 28, day 42 and day 56 (week 8) and day 112 (Week 16)
Blood analysis
Blood sample will be collected for analyse of safety (blood count/liver and kidney functions, electrolytes) at day 0 and day 56
Cardiac monitoring
Electrocardiogram will be realized at day 0, 28 and 56.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Patient, man or woman, aged from 35 to 75 years old
3. 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:
1. "pathological gambling" sub-score from 6 to 12 (included),
2. "buying" sub-score from 8 to 12 (included),
3. "hypersexuality" sub-score from 8 to 12 (included),
4. "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).
4. ICD onset after PD onset and after initiation of dopaminergic drugs
5. Patient treated by dopaminergic drugs for at least 3 months before randomization
6. 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)
7. Patient with health insurance
8. Patient/ guardian / curator who sign the written informed consent
9. 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.
Exclusion Criteria
2. Patient who have a known hypersensitivity to the study treatment, based on known allergies to drugs of the same class
3. Stroke, uncontrolled serious medical illness, myocardial infarction, congestive heart failure, cardiac function disorders, within 6 months before randomization
4. Patient with history of long QT syndrome
5. Patient with long QTcB detected with ECG at inclusion visit (\> 450 ms)
6. Patient treated with antipsychotic drugs during the last three months before randomization
7. Patient treated with concomitant medication leading to torsade de pointes (TdP) without discontinuation ≥ 5 half-lives before randomization (please refer to medications list with known risks of TdP on appendix XVII.5.10 and check website https://crediblemeds.org/index.php/tools/ for the most up-to-date information)
8. Patient with hydro-electrolytics troubles, particularly hypokaliemia or hypocalcemia not corrected, at inclusion visit or assessed no later than 8 days before randomization. To be eligible, the patient's electrolyte values should be within the following limits:
3.5 ≤ K+ ≤ 5 mmol/L 135 ≤ Na+ ≤ 145 mmol/L 2,20 ≤ Ca2+ ≤ 2,60 mmol/L
9. Patient treated with a strong or moderate CYP3A4 inducer: carbamazepine, rifampicin, phenytoin, modafinil, efavirenz or a strong inhibitor of CYP3A4: azole antifungals, protease inhibitors, macrolids, without discontinuation ≥ 5 half-lives before randomization
10. Patient treated with medicinal plants interacting with CYP3A4 without discontinuation ≥ 5 half-lives before randomization (Echinacea (E.pupurea, E.angustifolia and E.pallida), Piperina, Artemisia, St. John's Wort and Ginkgo
11. Patient with Montreal Cognitive Assessment (MoCA) (Nasreddine et al., 2005) score \< 20 (to exclude patients likely with dementia) at inclusion visit (Papay et al., 2014).
12. Patient suffering from severe depression or marked suicidal thoughts (score \> 3 on the suicidal thoughts item of the MADRS) at inclusion visit (Papay et al., 2014)
13. History of DBS within the past year before randomization, or change in stimulation parameters less than one month prior to randomization
14. Hematologic or solid malignancy diagnosis within 5 years prior to randomization.
\[Note: Subjects with a history of localized skin cancer, basal cell or squamous cell carcinoma, may be enrolled in the study as long as they are cancer free prior to randomization. Subjects with other localized cancers (without metastatic spread) who have previously completed their course of treatment more than 5 years prior to randomization, are not currently receiving treatment and have been in remission may be enrolled only if, in the opinion of the Investigator, there is no expectation for recurrence or further cancer treatment during the study period. Antihormonal therapy (e.g., tamoxifen) is allowed if the subject's cancer is in remission and the subject is on stable maintenance therapy to reduce their risk of recurrence.\]
15. Patient suffering from severe renal impairment define as CrCL\<30 mL/min, Cockcroft-Gault at inclusion visit or assessed no later than 8 days before randomization
16. Clinically significant hepatic impairment
17. Concurrent participation in another research involving a drug or medical device
18. Patient with language barriers precluding adequate understanding or co-operation or who, in the opinion of the investigator, should not participate in the trial
19. Treatment with an investigational treatment within 30 days prior to randomization
20. Woman pregnant, nursing or of childbearing potential age without effective contraception methods\* or intends to become pregnant.
* an effective contraception method is defined as implants, oral oestro-progestative contraceptives or progestative which inhibit ovulation contraceptives (e.g, desogestrel), or double barrier method (condom plus spermicide or diaphragm plus spermicide) or levonorgestrel intrauterine devices, or vasectomized partner (confirmed with two negative spermograms).
35 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
NS-PARK
UNKNOWN
EUCLID Clinical Trial Platform
OTHER
F-CRIN
UNKNOWN
ACADIA Pharmaceuticals Inc.
INDUSTRY
University Hospital, Strasbourg, France
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Mathieu ANHEIM, MD
Role: PRINCIPAL_INVESTIGATOR
CHRU Strasbourg
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Service de Neurologie and CIC -CHU Besançon
Besançon, , France
SERVICE DE NEUROLOGIE C, Unité mouvement anormaux/Centre expert Parkinson, CHU de Lyon, Hopital neurologique Pierre Wertheimer
Bron, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson CHU Clermont-Ferrand, Hopital Gabriel Montpied
Clermont-Ferrand, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, Hopital Henri Mondor
Créteil, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Grenoble Alpes
Grenoble, , France
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, CHU de Lille, Hopital Roger Salengro
Lille, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Limoges
Limoges, , France
SERVICE DE NEUROLOGIE, Unité Mouvement Anormaux/Centre expert Parkinson, Hopital de la Timone
Marseille, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Nantes, Hopital Laennec
Nantes, , France
SERVICE DE NEUROLOGIE Centre Expert Parkinson Hopital de la Pitié-Salpêtrière
Paris, , France
Centre d'Inverstigation Clinique, CHU de Poitiers
Poitiers, , France
SERVICE DE NEUROLOGIE, CHU de REIMS
Reims, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rennes, Hopital Pontchaillou
Rennes, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CHU de Rouen, Hopital Charles Nicolle
Rouen, , France
SERVICE DE NEUROLOGIE Unité de Mouvements Anormaux/Centre expert Parkinson, CHU de Strasbourg, Hopital de Hautepierre
Strasbourg, , France
SERVICE DE NEUROLOGIE, Unité Mouvements Anormaux/Centre expert Parkinson, CIC, CHU de Toulouse, Hopital Pierre-Paul Riquet
Toulouse, , France
Countries
Review the countries where the study has at least one active or historical site.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
6398
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.