Pimavanserin for Aggression
Recruiting in Palo Alto (17 mi)
Overseen byEmil F. Coccaro
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Ohio State University
Must not be taking: Antipsychotics, Opiates
Disqualifiers: Bipolar, Schizophrenia, Depression, others
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?The investigators are studying how certain drugs can reduce anger outbursts in people with anger problems. In this study the investigators seek to determine if a single 34 mg (two 17 mg tablets) oral dose of the 5-HT2a receptor blocker, pimavanserin, will reduce aggressive responding in individuals with impulsive aggression (Intermittent Explosive Disorder: IED) on a laboratory task that assesses aggression (Taylor Aggression Paradigm: TAP). We will also be examining how this drug impacts hostile social cognition e.g., hostile attribution). If pimvanserin reduces aggression in this study a next step would be a placebo-controlled treatment trial of pimavanserin in study participants with IED. Participation will first involve a remote (e.g., TEAMS) screening session. If potential study participants appear eligible they will come into the lab for an in-person session where participants will complete interviews and questionnaires and have a medical evaluation (including a physical exam, electrocardiogram, and screens for alcohol and drug use). During the next study session, participants will complete a diagnostic interview and a series of questionnaires, all of which can all take place on-line. During the next two sessions (which will be in-person) participants will undergo two (2) study sessions during which study participants will be given a study drug (orally). The drug given, pimavanserin, is currently available and is known to block serotonin receptors thought to be involved in regulating anger. After participants take the study drug, study participants will complete questionnaires and computer tasks for assessment of aggression and of hostile social cognition. Each of these two in-person study sessions will take at least eight (8) hours. A final on-line session will be done to make certain the investigators have all the data required by the study protocol.
Will I have to stop taking my current medications?
The trial requires participants to be free of anti-psychotic medication for two weeks before starting. If you are on such medications, you will need to stop taking them for this period.
What data supports the effectiveness of the drug Pimavanserin for aggression?
Pimavanserin is effective in treating hallucinations and delusions in Parkinson's disease psychosis, showing significant improvement in symptoms compared to placebo in clinical trials. Its unique action on serotonin receptors may also help with psychosis in other conditions, suggesting potential benefits for aggression.
12345Is pimavanserin safe for humans?
Pimavanserin, also known as Nuplazid, has been shown to be generally safe in humans, with clinical trials indicating it does not worsen motor symptoms in patients with Parkinson's disease psychosis. It has a relatively benign safety profile, but like many antipsychotics, it carries a warning for increased risk of mortality in elderly patients with dementia-related psychosis.
13456How is the drug Pimavanserin unique for treating aggression?
Pimavanserin is unique because it is a selective serotonin 2A receptor inverse agonist and antagonist, originally approved for treating hallucinations and delusions in Parkinson's disease psychosis, which makes it different from other treatments that may not target this specific receptor.
478910Eligibility Criteria
This trial is for adults aged 21-55 with impulsive aggression or Intermittent Explosive Disorder. They must be in good physical health, not on psychotropic meds for the last four weeks, and able to consent. Women must test negative for pregnancy.Inclusion Criteria
I am between 21 and 55 years old and can make my own medical decisions.
I haven't taken any anti-psychotic medication for the last two weeks.
Participants with a current (or past) DSM-5 diagnosis of Intermittent Explosive Disorder (IED)
+1 more
Exclusion Criteria
Clinically significant medical condition
Unwilling/unable to sign informed consent document
Current alcohol/drug use disorder of greater than mild severity
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
1 visit (virtual)
Baseline Assessment
Participants complete interviews, questionnaires, and a medical evaluation
1 day
1 visit (in-person)
Treatment
Participants receive a single dose of pimavanserin or placebo and complete aggression and social cognition tasks
2 days
2 visits (in-person)
Data Collection
Final online session to ensure all data required by the study protocol is collected
1 day
1 visit (virtual)
Follow-up
Participants are monitored for any adverse effects and overall safety after treatment
2 weeks
Participant Groups
The study tests if a single dose of Pimavanserin (34 mg), which blocks certain serotonin receptors, can reduce aggressive behavior and alter hostile social cognition in people with anger issues compared to a placebo.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: PimavanserinExperimental Treatment1 Intervention
One single dose of pimavanserin (34 mg oral)
Group II: PlaceboPlacebo Group1 Intervention
One single dose of matching placebo
Pimavanserin is already approved in United States for the following indications:
🇺🇸 Approved in United States as Nuplazid for:
- Hallucinations and delusions associated with Parkinson's disease psychosis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
The Ohio State University College of MedicineColumbus, OH
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Who Is Running the Clinical Trial?
Ohio State UniversityLead Sponsor
ACADIA Pharmaceuticals Inc.Industry Sponsor
References
Pimavanserin (Nuplazid™) for the treatment of Parkinson disease psychosis: A review of the literature. [2022]Label="INTRODUCTION" NlmCategory="BACKGROUND">Pimavanserin (Nuplazid™) is an atypical antipsychotic currently indicated for the treatment of hallucinations and delusions associated with Parkinson disease psychosis. The antipsychotic effects of this new agent are believed to occur via selective inverse agonist activity at serotonin 5-HT2a receptors.
Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis. [2021]Objective: Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of FDA.gov and clinicaltrials.gov yielded additional studies. English-language studies of pimavanserin for PDP were evaluated. Animal studies were excluded. Randomized, controlled trials (RCTs) were prioritized. Results: Four RCTs were identified. In each, pimavanserin was well-tolerated with few adverse effects and no worsening of motor symptoms. A Phase II trial displayed a nonsignificant trend toward Scale for Assessment of Positive Symptoms (SAPS) improvement (p=0.09), with significant benefits in secondary efficacy markers. However, two Phase III trials, including one that was terminated early, failed to show significant SAPS improvement. A third Phase III trial with an improved research design utilized a nine-item subset of the SAPS, the SAPS-PD, as the primary outcome and demonstrated that pimavanserin 40mg was effective in improving PDP compared to placebo (p=0.0014, effect size=0.50). Secondary outcomes were also significantly improved: Clinical Global Impression of Severity (CGI-S) (p=0.0007, effect size=0.52) and Clinical Global Impression of Improvement (CGI-I) (p=0.0011, effect size=0.51), caregiver burden (p=0.0016, effect size=0.50), nighttime sleep (p=0.0446, effect size=0.31), and daytime wakefulness (p=0.012, effect size=0.39). Conclusion: Evidence suggests pimavanserin attenuates PDP symptoms with few adverse effects and little risk of worsening motor function. With limited treatment options for PDP, pimavanserin represents an important therapeutic innovation.
Pimavanserin. [2017]Pimavanserin (ACP-103) is a selective inverse agonist of the 5-hydroxytryptamine 2A (5-HT2A) receptor intended to treat patients with Parkinson's disease psychosis (PDP). Currently there are no FDA-approved medications in the United States for the treatment of PDP, although on September 2, 2014, the United States Food and Drug Administration granted breakthrough therapy status to pimavanserin, highlighting the unmet need for therapeutics in this class. Most antipsychotic medications worsen motor dysfunction due to dopamine antagonism, and all carry a black box warning for an increased risk of mortality in elderly patients with dementia-related psychosis. Data from phase II and phase III clinical trials suggest that pimavanserin is a safe and effective treatment option for PDP. Trial results indicate a significant reduction in hallucinations and delusions in patients with PDP without worsening motor symptoms. Additional studies are ongoing for the treatment of Alzheimer's psychosis, schizophrenia and insomnia. Such promising outcomes warrant a review of the available literature regarding pimavanserin and its use in the treatment of PDP symptoms.
Pimavanserin: First Global Approval. [2022]Pimavanserin (Nuplazid™) is a selective and potent serotonin 2A (5-HT2A) receptor inverse agonist and antagonist developed by ACADIA Pharmaceuticals that has been approved in the US as a treatment for patients with hallucinations and delusions associated with Parkinson's disease psychosis. Up to 60 % of patients with Parkinson's disease may develop Parkinson's disease psychosis, which is associated with increased morbidity and mortality and has few treatment options. This article summarizes the milestones in the development of pimavanserin leading to this first approval for the treatment of hallucinations and delusions in patients with Parkinson's disease psychosis.
Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis. [2018]Label="INTRODUCTION">Pimavanserin is the first FDA-approved atypical antipsychotic drug indicated for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Areas covered: This review focuses on the preclinical discovery of pimavanserin. It analyzes the pharmacological, behavioral and molecular mechanisms of pimavanserin and their contribution to the therapeutic advantages of the drug as reported in published preclinical and clinical studies, press releases and product labels. Expert opinion: Pimavanserin exhibits a unique pharmacological profile with nanomolar affinity at serotonin 5-HT2A and 5-HT2C receptors. Functionally, it acts as a potent inverse agonist at 5-HT2A receptors, with selectivity over 5-HT2C receptors and no appreciable activity at other neurotransmitter receptors. Behavioral studies found that pimavanserin reversed impaired behaviors in animal models predictive of antipsychotic activity, and with no impairment of motor functions. The drug exhibits long plasma half-life (57 hours), which support its once/day administration. A pivotal phase III clinical trial demonstrated significant improvement in PDP symptoms in patients receiving pimavanserin compared to placebo-treated patients. The drug also displayed relatively benign safety and tolerability profiles. Pimavanserin's mechanism of action might contribute to its unique psychopharmacological properties in the improved treatment of PDP, and perhaps psychosis in other diseases including schizophrenia and dementia-related psychosis.
Changing the treatment paradigm for Parkinson's disease psychosis with pimavanserin. [2019]Introduction: Parkinson's disease psychosis (PDP) may affect up to 60% of patients with Parkinson's disease over the course of their disease, and is associated with poor prognosis, including increased risks of mortality and nursing home placement. PDP treatments have been limited to off-label use of atypical antipsychotics, most of which pose risks of worsened motor symptoms and other potential adverse events (AEs) due to their dopamine receptor blockade and additional off-target receptor affinities. Pimavanserin is a highly selective 5-HT2A inverse agonist and poses no known risks for worsening of parkinsonism or other off-target receptor AEs. Pimavanserin is the first and only medication approved for PDP treatment. Areas covered: This review covers estimated prevalence, clinical characteristics, diagnostic criteria, and risk factors for PDP; the hypothetical progression of PDP; management of PDP including use of antipsychotics; pharmacology and clinical trial data on pimavanserin; and expert opinion on PDP treatment. The NLM/PubMed database was searched for papers using the search terms of "PDP" AND "treatment" AND "pimavanserin" for the last 10 years. Expert opinion: The recent insights into PDP pathophysiology and approval of the only medication specifically to treat PDP are key advances that should improve the recognition, diagnosis, and management of PDP.
Pimavanserin in Alzheimer's Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms. [2020]Pimavanserin is a 5-HT2A receptor inverse agonist/antagonist and is approved in the United States for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.
Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome. [2022]Pimavanserin is a serotonin 2A receptor inverse agonist and antagonist used for the treatment of hallucinations and delusions in Parkinson's disease psychosis. Numerous studies support a modulatory role of serotonin in Tourette syndrome (TS).
Can pimavanserin help patients with Parkinson disease psychosis? [2020]Pimavanserin is a first-in-class selective serotonin 5-HT2A receptor inverse agonist approved for the treatment of Parkinson disease psychosis. This article discusses pimavanserin's mechanism of action, which patients are appropriate candidates for therapy, adverse reactions, and appropriate dosing.
(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand. [2016]Pimavanserin is a selective serotonin 2A receptor (5-HT2AR) inverse agonist that has shown promise for treatment of psychotic symptoms in patients with Parkinson's disease. Here, we detail the (11)C-labeling and subsequently evaluate pimavanserin as a PET-radioligand in pigs. [(11)C]Pimavanserin was obtained by N-methylation of an appropriate precursor using [(11)C]MeOTf in acetone at 60°C giving radiochemical yields in the range of 1-1.7GBq (n=4). In Danish Landrace pigs the radio ligand readily entered the brain and displayed binding in the cortex in accordance with the distribution of 5-HT2ARs. However, this binding could not be blocked by either ketanserin or pimavanserin itself, indicating high nonspecific binding. The lack of displacement by the 5-HT2R antagonist and binding in the thalamus suggests that [(11)C]pimavanserin is not selective for the 5-HT2AR in pigs.