Pimavanserin vs. Quetiapine for the Treatment Parkinson's Psychosis (C-SAPP)
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|ClinicalTrials.gov Identifier: NCT04373317|
Recruitment Status : Not yet recruiting
First Posted : May 4, 2020
Last Update Posted : October 1, 2020
Patients with Parkinson's disease (PD) sometimes experience symptoms affecting their movement, such as slowness, tremor, stiffness, and balance or walking problems. Many patients also have other symptoms not related to movement, called non-motor symptoms, which may affect one's mood or emotions, memory or thinking, or cause one to see or hear things that aren't real (hallucinations) or believe things that aren't true (delusions). Hallucinations or delusions, together called psychosis, occur in up to 60% of PD patients at some point in time. Parkinson's disease psychosis can sometimes be associated with decreased quality of life, increased nursing home placement, increased rate of death, and greater caregiver burden. There are approximately 50,000 Veterans with Parkinson's disease receiving care in the VA, and up to 30,000 (60%) of them will experience psychosis at some point in time.
Quetiapine is an antipsychotic drug approved by the Food and Drug Administration (FDA) that is the most commonly used medication to treat PD psychosis, but more studies are needed to determine if it works for this condition and is also well tolerated and safe. Pimavanserin is a newer antipsychotic drug approved by the Food and Drug Administration (FDA) specifically to treat PD psychosis, but more studies are needed to determine if it works and its safety.
The purpose of this research is to gather additional information on the safety and effectiveness of both Quetiapine and Pimavanserin. By doing this study, the investigators hope to learn which of these medications is the most effective course of treatment for people with PD psychosis. Your individual participation in this research will last approximately 54 weeks.
|Condition or disease||Intervention/treatment||Phase|
|Parkinson's Disease Psychosis||Drug: Pimavanserin Drug: Quetiapine||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||358 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Two active treatments will be administered in this RCT, with 1:1 treatment assignment to either quetiapine or pimavanserin. Both active treatments are FDA-approved antipsychotics.|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||In order to facilitate titrations, study drug will be provided in blister cards with a sufficient number of over-encapsulated drug to bridge participants to their next titration step. Each blister card will contain a one-week supply of study drug. Because dosing will be nightly, and the study will use a combination of quetiapine strengths for all protocol-specified quetiapine doses, participants in both treatment groups will take two identical capsules both of which containing the protocol-specified nightly dose. For example, if a participant is randomized to quetiapine and is up-titrated from 50 to 100 mg ER, this participant will take 2 identical capsules, each containing 50 mg of ER quetiapine. Similarly, participants randomized to pimavanserin will take two capsules every night, one containing a placebo capsule, and the other containing 34 mg of pimavanserin.|
|Official Title:||CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)|
|Estimated Study Start Date :||January 1, 2021|
|Estimated Primary Completion Date :||January 1, 2024|
|Estimated Study Completion Date :||July 1, 2024|
Active Comparator: Pimavanserin 34mg
All participants assigned to pimavanserin will receive the FDA-approved dose of 34mg (equivalent to 40 mg pimavanserin tartrate) daily without titration; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability.
Pimavanserin is a new antipsychotic agent, and pure 5HT-2A inverse agonist, that was approved by the FDA recently (2016) for the treatment of PDP.
Active Comparator: Quetiapine
Quetiapine extended release will be titrated as shown in the following table. During the 8-week treatment phase, there is a maximum of 6 weeks for titration.
Visit/call Quetiapine Dose (Flexible)Quetiapine Notes Baseline visit (Visit 00)25 mg IR QHSAll participants must be up-titrated to at least 50 mg/day at week 1 Week 1 call (Visit 01)50 mg XR QHSUp-titration Week 3 visit (Visit 03)100 mg XR QHS (requiring two 50-mg quetiapine XR capsules)Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 5 visit (Visit 05)150 mg quetiapine XR QHSUp- or down-titration as appropriate based on psychosis symptoms and tolerability Week 6 call (Visit 06)200 mg quetiapine XR QHSUp- or down-titration as appropriate based on psychosis symptoms and tolerability
Quetiapine, which is a mixed serotonin and dopamine receptor antagonist but also binds to many other brain receptors (e.g., adrenergic, cholinergic, histaminergic receptors), is by far the most commonly used AP for PDP (at least 70% of prescriptions) and does not require special monitoring.
- CGI-I Psychosis [ Time Frame: 8 Weeks ]CGI-I (for psychosis). The Clinical Global Impressions (CGI) scale is a brief, well-established research rating tool used to quantify and track patient progress and treatment response over time. It was originally developed to be used in clinical trials on mental health to provide an assessment of the clinician's view of the patient's global functioning over time with a study medication. The CGI comprises two measures, one of which is Improvement (CGI-I) from the initiation of treatment. It is scored 1 to 7. The CGI-I is used to assess how much the patient's illness has improved or worsened relative to baseline when the intervention was started (1-Very much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse). The CGI-I can also be used to assess specific domains, including psychosis (this study's primary outcome) and parkinsonism (a secondary outcome).
- SAPS-PD [ Time Frame: 8 Weeks ]The primary assessment of change in psychosis severity will be the score on the 9-item Parkinson's disease-adapted Scale for Assessment of Positive Symptoms (SAPS-PD).59 The SAPS-PD scale is designed to assess positive symptoms, including hallucinations, delusions, bizarre behavior, and positive formal thought disorder. A standard clinical interview with probing questions is used to evaluate the participant's symptoms. Items include: 1) Auditory Hallucinations; 2) Voices Conversing; 3) Somatic or Tactile Hallucinations; 4) Visual Hallucinations; 5) Global Rating of Severity of Hallucinations; 6) Persecutory Delusions; 7) Delusions of Jealousy; 8) Ideas and Delusions of Reference; and 9) Global Rating of Severity of Delusions. Each item is given a score ranging 0 to 5 (0-None, 1-Questionable, 2-Mild, 3-Moderate, 4-Marked, 5-Severe). Thus, total scores for SAPS-PD ranges 0-45.
- MDS-UPDRS III [ Time Frame: 8 Weeks ]The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination; MDS-UPDRS III) has 33 scores across 18 items (each score 0-4, range of total score 0-132, with higher scores indicating more severe motor symptoms) is completed by a trained rater during an examination of the patient, and is the most commonly-used assessment of parkinsonism in clinical trials. MDS-UPDRS III includes ratings for tremor, slowness (bradykinesia), stiffness (rigidity), and gait/balance. The MDS-UPDRS III will be administered to all participants (quetiapine or pimavanserin) at each in-person visit (baseline, 3 weeks, 5 weeks, and 8 weeks). Administration will also occur at weeks 10, 13, 15, and 18 for non-responders at week 8, and months 3, 6, 9, and 12 for responders at week 8. The CGI-I for parkinsonism will similarly be assessed at these study visits to address this secondary outcome.
- Zarit Caregiver Burden Scale [ Time Frame: 8 Weeks ]The Zarit Burden Interview (ZBI) is a 22-item self-report inventory that examines burden associated with functional/behavioral impairments and the home care situation.64 It was originally developed to measure subjective burden among caregivers of adults with dementia. The items are worded subjectively, focusing on the affective response of the caregiver. Each question is scored on a 5-point Likert scale ranging from 0 to 4 (0-Never, 1-Rarely, 2-Sometimes, 3-Frequently, 4-Nearly always). The ZBI total score ranges from 0 (low burden) to 88 (high burden), the sum of the scores from all 22 questions. Interpretation of the total scores is typically: 1) 0-21 little or no burden; 2) 21-40 mild to moderate burden; 3) 41-60 moderate to severe burden; and 4) 61-88 severe burden. The ZBI will be administered to all participants' informed other at baseline and treatment phase visits of Weeks 5 and 8.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04373317
|Contact: Daniel Weintraub, MD||(215) 823-5800 ext firstname.lastname@example.org|
|Contact: John E Duda, MD||(215) email@example.com|
|United States, Pennsylvania|
|Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Daniel Weintraub, MD 215-823-5800 ext 5934 firstname.lastname@example.org|
|Study Chair: Daniel Weintraub, MD|
|Study Chair:||Daniel Weintraub, MD||Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA|