Pimavanserin and Aggression and Social Cognition.

NCT05895513 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2023H0014
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Intermittent Explosive Disorder

Keywords

Aggression; Intermittent Explosive Disorder; Hostile Social Cognition; 5-HT-2a Receptor Antagonist; Pimavanserin

Outcome Measures

Primary Outcomes (1)

• Aggressive Responding on the Taylor Aggression Paradigm (TAP)

  In the TAP, the subject competes against a fictitious opponent in a reaction time game during which the investigator manipulates provocation by having the "opponent" select increasing (mild) electric shock levels (i.e., a physically aggressive threat) which then elicits aggressive responding to the "confederate" when he/she loses a reaction-time task. Subjects can select shock from level 1 to level 9, and to select a "high" (10 level) or a "very high" (20 level) shock. The total number of "High" / "Very High" (10/20) shocks selected for the opponent is the outcome for heightened aggression in this study.

  The TAP will be done about five (5) hours after administration of pimavanserin and after placebo.

Secondary Outcomes (1)

• Social-Emotional Information Processing (Video-SEIP)

  The V-SEIP will be done about five (5) hours after administration of pimavanserin and after placebo.

Study Arms (2)

Pimavanserin

EXPERIMENTAL

One single dose of pimavanserin (34 mg oral)

Drug: Pimavanserin 34 mg

Placebo

PLACEBO COMPARATOR

One single dose of matching placebo

Drug: Placebo

Interventions

Pimavanserin 34 mg DRUG

5HT-2a receptor antagonist

Also known as: Nuplazid

Pimavanserin

Placebo DRUG

Inactive Comparator

Placebo

Eligibility Criteria

• Age: 21 Years - 55 Years
• Gender Eligibility Details: Biological sex assigned at birth.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants will have a current (or past) DSM-5 diagnosis of Intermittent Explosive Disorder (IED) or have a Life History of Aggression (LHA) score equal or greater than 12. In addition, all participants must meet the following criteria:
• Participant is between 21 and 55 years of age and is able to give informed consent.
• Participant is physically healthy as confirmed by medical history, physical evaluation, ECG, and (in females) has a negative pregnancy test.
• Two weeks free of anti-psychotic medication.

You may not qualify if:

• All subjects with the following are excluded from study:
• Clinically significant medical condition.
• Prolonged QT-Interval ( \> 0.45 / \> 0.47 seconds for males/females).
• Life history of bipolar disorder / schizophrenia / organic mental syndrome or intellectual disability.
• Current major depressive disorder with a BDI score \> 32.
• Current alcohol / drug use disorder of greater than mild severity.
• Current suicidal ideation.
• Allergy, or other contraindication, to Pimavanserin.
• Current treatment with opiates or any agents that affect pain threshold.
• Unwilling/unable to sign informed consent document.

Sponsors & Collaborators

• Ohio State University: lead
• ACADIA Pharmaceuticals Inc.: collaborator

Study Sites (1)

The Ohio State University College of Medicine

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (20)

• Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry. 1976 Oct;33(10):1193-7. doi: 10.1001/archpsyc.1976.01770100055005.

  PMID: 971028 BACKGROUND

• Berman ME, McCloskey MS, Fanning JR, Schumacher JA, Coccaro EF. Serotonin augmentation reduces response to attack in aggressive individuals. Psychol Sci. 2009 Jun;20(6):714-20. doi: 10.1111/j.1467-9280.2009.02355.x. Epub 2009 May 5.

  PMID: 19422623 BACKGROUND

• Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK. Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry. 1982 Jun;139(6):741-6. doi: 10.1176/ajp.139.6.741.

  PMID: 6177256 BACKGROUND

• Coccaro EF. Intermittent explosive disorder as a disorder of impulsive aggression for DSM-5. Am J Psychiatry. 2012 Jun;169(6):577-88. doi: 10.1176/appi.ajp.2012.11081259.

  PMID: 22535310 BACKGROUND

• Coccaro EF, Lee RJ. Disordered Aggression and Violence in the United States. J Clin Psychiatry. 2020 Mar 17;81(2):19m12937. doi: 10.4088/JCP.19m12937.

  PMID: 32220154 BACKGROUND

• Coccaro EF, Fanning JR, Fisher E, Couture L, Lee RJ. Social emotional information processing in adults: Development and psychometrics of a computerized video assessment in healthy controls and aggressive individuals. Psychiatry Res. 2017 Feb;248:40-47. doi: 10.1016/j.psychres.2016.11.004. Epub 2016 Nov 8.

  PMID: 28012305 BACKGROUND

• Coccaro EF, Fanning JR, Keedy SK, Lee RJ. Social cognition in Intermittent Explosive Disorder and aggression. J Psychiatr Res. 2016 Dec;83:140-150. doi: 10.1016/j.jpsychires.2016.07.010. Epub 2016 Jul 16.

  PMID: 27621104 BACKGROUND

• Coccaro EF, Kavoussi RJ, Sheline YI, Berman ME, Csernansky JG. Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding. Neuropsychopharmacology. 1997 Mar;16(3):211-6. doi: 10.1016/S0893-133X(96)00194-7.

  PMID: 9138437 BACKGROUND

• Coccaro EF, Lee R, Kavoussi RJ. Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology. 2010 Jan;35(2):435-44. doi: 10.1038/npp.2009.148.

  PMID: 19776731 BACKGROUND

• Coccaro EF, Lee RJ, Kavoussi RJ. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry. 2009 Apr 21;70(5):653-62. doi: 10.4088/JCP.08m04150.

  PMID: 19389333 BACKGROUND

• Coccaro EF, Noblett KL, McCloskey MS. Attributional and emotional responses to socially ambiguous cues: validation of a new assessment of social/emotional information processing in healthy adults and impulsive aggressive patients. J Psychiatr Res. 2009 Jul;43(10):915-25. doi: 10.1016/j.jpsychires.2009.01.012. Epub 2009 Apr 3.

  PMID: 19345371 BACKGROUND

• Coccaro EF, Siever LJ, Klar HM, Maurer G, Cochrane K, Cooper TB, Mohs RC, Davis KL. Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry. 1989 Jul;46(7):587-99. doi: 10.1001/archpsyc.1989.01810070013002.

  PMID: 2735812 BACKGROUND

• Lee R, Coccaro, E.F. Neurotransmitters and Intermittent Explosive Disorder. In: Intermittent Explosive Disorder, EF Coccaro and MS McCloskey (eds). 2019:87-110.

  BACKGROUND

• Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci. 1983 Dec 26;33(26):2609-14. doi: 10.1016/0024-3205(83)90344-2.

  PMID: 6198573 BACKGROUND

• McCloskey MS, Berman ME. Laboratory measures of aggression: The Taylor Aggression Paradigm. In: EF C, ed. Aggression: Psychiatric Assessment and Treatment. Marcel Dekker; 2003:397.

  BACKGROUND

• Meyer JH, Wilson AA, Rusjan P, Clark M, Houle S, Woodside S, Arrowood J, Martin K, Colleton M. Serotonin2A receptor binding potential in people with aggressive and violent behaviour. J Psychiatry Neurosci. 2008 Nov;33(6):499-508.

  PMID: 18982172 BACKGROUND

• Oquendo MA, Russo SA, Underwood MD, Kassir SA, Ellis SP, Mann JJ, Arango V. Higher postmortem prefrontal 5-HT2A receptor binding correlates with lifetime aggression in suicide. Biol Psychiatry. 2006 Feb 1;59(3):235-43. doi: 10.1016/j.biopsych.2005.06.037. Epub 2005 Sep 2.

  PMID: 16140277 BACKGROUND

• Rosell DR, Thompson JL, Slifstein M, Xu X, Frankle WG, New AS, Goodman M, Weinstein SR, Laruelle M, Abi-Dargham A, Siever LJ. Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry. 2010 Jun 15;67(12):1154-62. doi: 10.1016/j.biopsych.2010.03.013.

  PMID: 20434136 BACKGROUND

• Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Dwork AJ, Mann JJ, Arango V. Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity. Transl Psychiatry. 2018 Dec 14;8(1):279. doi: 10.1038/s41398-018-0309-1.

  PMID: 30552318 BACKGROUND

• Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet. 1983 Jan 29;1(8318):214-6. doi: 10.1016/s0140-6736(83)92590-4. No abstract available.

  PMID: 6130248 BACKGROUND

MeSH Terms

Conditions

Disruptive, Impulse Control, and Conduct Disorders; Aggression

Interventions

pimavanserin

Condition Hierarchy (Ancestors)

Mental Disorders; Aberrant Motor Behavior in Dementia; Behavioral Symptoms; Behavior; Social Behavior

Study Officials

• Emil F. Coccaro

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew A. Timmins, PhD

CONTACT

614-257-2119; matthew.timmins@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo (tablets identical to active drug)
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: June 8, 2023
• Study Start: August 1, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)