Pitolisant Effects on Affect and Cognition Exploratory Study (PEACE Study) (PEACE)

May 4, 2023 updated by: University of Oxford

An fMRI Investigation of the Effects of Selective Histamine-3 Receptor Antagonism on Cognitive and Emotional Processing in Healthy Individuals

The goal of this study is to investigate the effects of selective histamine 3 antagonist pitolisant on brain function and cognition in healthy individuals. The main questions it aims to answer are:

  1. Does pitolisant alter functional activity in brain regions linked to reward and cognitive processing during rest or cognitive task performance?
  2. Does pitolisant alter cognitive ability across a range of psychological domains, including working memory, executive functioning and emotional processing?

Participants will undertake fMRI scanning in addition to a battery of tasks designed to measure cognitive and emotional processing after taking a single dose of pitolisant or placebo. Researchers will compare differences in functional activity, cognition and emotional processing across the pitolisant and placebo groups.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Cognitive and affective processing are underpinned by monoaminergic neurotransmission and neurosteroid systems, yet there are many aspects of these systems that remain unknown in humans. In particular, monoaminergic histamine 3 (H3) receptors are abundant in CNS regions underpinning cognitive processing (prefrontal cortex, hippocampus, and striatum), yet the role of these receptors in humans remains unclear. Evidence from animal models suggests H3R antagonism improves cognitive functioning, however these specific effects are yet to be examined in humans. Similarly, the function of sigma-1 (σ-1) receptors in the brain is not well understood in humans despite strong evidence of pro-cognitive effects in animal models.

The study will investigate the effect of pitolisant, a dual H3R antagonist and σ-1R agonist, on cognitive and affective processing, in addition to changes in functional connectivity. These effects will be measured with a battery of neuropsychological tasks (e.g., Affective Go/No-Go Task; Adaptive dual n-back task), self-rated measures of cognitive function (PDQ), and resting state fMRI and fMRI data acquisition during the verbal n-back and memory encoding tasks.

Study Type

Interventional

Enrollment (Anticipated)

56

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Oxford, United Kingdom
        • Recruiting
        • Department of Psychiatry, University of Oxford
        • Contact:
        • Contact:
        • Principal Investigator:
          • Susannah E Murphy, DPhil
        • Sub-Investigator:
          • Catherine J Harmer, DPhil

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the research
  • Not currently taking any medications which may interfere with pitolisant, including psychoactive medications
  • Not currently using antihistaminergic medication
  • Aged 18-45 years
  • Male or female
  • Sufficiently fluent English to understand and complete cognitive tasks and questionnaires
  • Body Mass Index above or below 18-30
  • Right handed

Exclusion Criteria:

  • Current pregnancy (as determined by urine pregnancy test taken during screening visit), planning to become pregnant or breast feeding
  • Any past or current history of severe and/or serious psychiatric disorder, including but not limited to schizophrenia, psychosis, bipolar affective disorder, major depressive disorder, obsessive compulsive disorder
  • Clinically significant abnormal values for urine drug screen, blood pressure measurement ( in accordance with AP20 'non-invasive blood pressure') and ECG. A participant with a clinical abnormality or parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
  • History of, or current medical conditions which, in the opinion of the investigator, may interfere with the safety of the participant or the scientific integrity of the study, including epilepsy/seizures, brain injury, hepatic or renal disease, acid-related gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions
  • Current or past history of drug or alcohol dependency
  • Severe lactose intolerance
  • Use of recreational drugs (e.g. cannabis, cocaine, amphetamines) within past 3 months
  • Participation in a study which uses the same computer tasks as those in the present study (determined by asking participants about previous studies participated in during screening) within past 3 months
  • Participation in a study that involves the use of a medication within the last three months
  • Smoking > 5 cigarettes per day
  • Consumption of a high amount of caffeine per day (> 400ml caffeine) (e.g., 5 or more cups of coffee)
  • Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator
  • Any contraindication to MRI scanning (e.g. metal objects inside the body, pacemakers, significant claustrophobia)
  • Not right handed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pitolisant
Two film-coated tablets (18mg x 2 [36mg]) for oral administration will be encapsulated in an opaque capsule.
Drug: Pitolisant 17.8 MG [Wakix]
Single dose pitoliosant (36mg)
Placebo Comparator: Placebo
Two lactose film-coated tablets (2 x 65mg [125mg]) will be encapsulated in an opaque capsule (identical to the experimental arm drug).
Drug: Placebo
Single dose placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BOLD signal levels during resting state fMRI sequence
Time Frame: 3-6 hours after single dose of drug or placebo.
Blood Oxygenation Level Dependent (BOLD) signal level in prior regions of interest (striatum, hippocampus and anterior cingulate cortex) in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
BOLD signal levels during fMRI memory encoding task
Time Frame: 3-6 hours after single dose of drug or placebo.
BOLD signal level in prior regions of interest during the task (hippocampus; perirhinal cortex) in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
BOLD signal levels during fMRI n-back task
Time Frame: 3-6 hours after single dose of drug or placebo.
BOLD signal level in prior regions of interest during the task (dorsolateral prefrontal cortex; hippocampus; anterior cingulate cortex) in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)
Time Frame: 3-6 hours after single dose of drug or placebo.
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT) in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
Number of inhibited 'no-go' responses during the affective Interference Go/No-Go Task performance
Time Frame: 3-6 hours after single dose of drug or placebo.
Number of inhibited 'no-go' responses during the affective Interference Go/No-Go Task in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task
Time Frame: 3-6 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
Accuracy of emotional labeling of facial expressions during the facial emotion recognition task
Time Frame: 3-6 hours after single dose of drug or placebo.
Accuracy of emotion labels (e.g. disgusted face) assigned by participants to expressive faces during the facial emotion recognition task in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
Accuracy of target selection during n-back fMRI task
Time Frame: 3-6 hours after single dose of drug or placebo.
Accuracy of target selection during n-back fMRI task in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.
Accuracy of stimuli labeling (novel or familiar) during fMRI memory encoding task
Time Frame: 3-6 hours after single dose of drug or placebo.
Accuracy of stimuli labeling (novel or familiar) during fMRI memory encoding task in pilosant group compared with the placebo group
3-6 hours after single dose of drug or placebo.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Oxford

Investigators

  • Principal Investigator: Susannah E Murphy, DPhil, University of Oxford

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2023

Primary Completion (Anticipated)

March 1, 2024

Study Completion (Anticipated)

March 1, 2024

Study Registration Dates

First Submitted

April 3, 2023

First Submitted That Met QC Criteria

May 4, 2023

First Posted (Actual)

May 9, 2023

Study Record Updates

Last Update Posted (Actual)

May 9, 2023

Last Update Submitted That Met QC Criteria

May 4, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEACE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data which has been fully de-identified may be shared with other academic and commercial organisations in the future, including those outside of the UK and the EU. Participants will be informed of this and specific consent to this is obtained within the Informed Consent Form.

IPD Sharing Time Frame

A few months after all data has been completed (ETA July 2024), unblinding has occurred (ETA April 2024), and all data analyses has been completed (ETA May 2024).

IPD Sharing Access Criteria

The data will be made publicly available. Access requests will not be required.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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