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

NCT05849675 | Completed

• 1 other identifier: PEACE
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Anhedonia; Cognitive Function

Keywords

Drug; fMRI; pharmaco-fMRI; Cognition; Histamine

Outcome Measures

Primary Outcomes (3)

• BOLD signal levels during resting state fMRI sequence

  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

  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

  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 Outcomes (6)

• Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)

  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

  3-6 hours after single dose of drug or placebo.

• Accuracy of target selection on the Colour Change Detection Task

  3-6 hours after single dose of drug or placebo.

• Accuracy of emotional labeling of facial expressions during the facial emotion recognition task

  3-6 hours after single dose of drug or placebo.

• Accuracy of target selection during n-back fMRI task

  3-6 hours after single dose of drug or placebo.

Study Arms (2)

Pitolisant

EXPERIMENTAL

Two film-coated tablets (18mg x 2 \[36mg\]) for oral administration will be encapsulated in an opaque capsule.

Drug: Pitolisant 17.8 MG [Wakix]

Placebo

PLACEBO COMPARATOR

Two lactose film-coated tablets (2 x 65mg \[125mg\]) will be encapsulated in an opaque capsule (identical to the experimental arm drug).

Drug: Placebo

Interventions

Pitolisant 17.8 MG [Wakix] DRUG

Single dose pitoliosant (36mg)

Pitolisant

Placebo DRUG

Single dose placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Anhedonia

Interventions

pitolisant

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Susannah E Murphy, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matched placebo capsule
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly allocated to one of two groups (pitolisant or placebo). This study uses a novel procedure known as variance minimisation (described in Sella, Raz \& Cohen Kadosh, 2021) to randomise participants allocation to the two intervention groups based on equalising baseline cognitive functioning and gender. Participants will receive a single dose of the drug (pitolisant, 36mg) or placebo, and undertake fMRI and cognitive/emotional assessment three hours after dose. The study is assessing the effect antagonising the H3 receptor on functional connectivity/cognitive ability, it is not an efficacy or safety study.

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: May 9, 2023
• Study Start: April 1, 2023
• Primary Completion: February 18, 2024
• Study Completion: May 8, 2024
• Last Updated: May 14, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• 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).
• Access Criteria: The data will be made publicly available. Access requests will not be required.

Locations

GB (1)