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

NCT ID: NCT05849675

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-01
• Study Completion Date: 2024-05-08

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. 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.

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.

Conditions

Anhedonia; Cognitive Function

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Pitolisant

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

Group Type: EXPERIMENTAL

Pitolisant 17.8 MG [Wakix]

Intervention Type: DRUG

Single dose pitoliosant (36mg)

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single dose placebo

Interventions

Pitolisant 17.8 MG [Wakix]

Single dose pitoliosant (36mg)

Intervention Type: DRUG

Placebo

Single dose placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susannah E Murphy, DPhil

Role: PRINCIPAL_INVESTIGATOR

University of Oxford

Locations

Department of Psychiatry, University of Oxford

Oxford, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

PEACE

Identifier Type: -

Identifier Source: org_study_id