AnhedoniaPEACENCT05849675
Pitolisant Effects on Affect and Cognition Exploratory Study (PEACE Study)
A study testing Pitolisant 17.8 MG [Wakix] in people with Anhedonia and Cognitive Function, run by University of Oxford at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Anhedonia, Cognitive Function
- What is being tested?
- Pitolisant 17.8 MG [Wakix]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2023to 8 May 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Department of Psychiatry, University of Oxford
Oxford
About this study
Official title: 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:
- Does pitolisant alter functional activity in brain regions linked to reward and cognitive processing during rest or cognitive task performance?
- 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.
Read the 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
- Being tested
- Pitolisant 17.8 MG [Wakix], Placebo
- Keywords
- Drug, fMRI, pharmaco-fMRI, Cognition, Histamine
- Medical subject headings
- Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pitolisant 17.8 MG [Wakix]Drug
Single dose pitoliosant (36mg)
PlaceboDrug
Single dose placebo
| Study group | Role | What they receive |
|---|---|---|
| Pitolisant | Experimental | Two film-coated tablets (18mg x 2 [36mg]) for oral administration will be encapsulated in an opaque capsule. Receives: 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). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Measured: 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)
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT) in pilosant group compared with the placebo group
Measured: 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
Number of inhibited 'no-go' responses during the affective Interference Go/No-Go Task in pilosant group compared with the placebo group
Measured: 3-6 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task
Accuracy of target selection on the Colour Change Detection Task in pilosant group compared with the placebo group
Measured: 3-6 hours after single dose of drug or placebo.
Accuracy of emotional labeling of facial expressions during the facial emotion recognition task
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
Measured: 3-6 hours after single dose of drug or placebo.
Accuracy of target selection during n-back fMRI task
Accuracy of target selection during n-back fMRI task in pilosant group compared with the placebo group
Measured: 3-6 hours after single dose of drug or placebo.
Accuracy of stimuli labeling (novel or familiar) during fMRI memory encoding task
Accuracy of stimuli labeling (novel or familiar) during fMRI memory encoding task in pilosant group compared with the placebo group
Measured: 3-6 hours after single dose of drug or placebo.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start1 Apr 2023
- Primary completion18 Feb 2024
- Study completion8 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnhedoniaStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Susannah E Murphy, DPhil, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05849675
- Sponsor's protocol ID
- PEACE
- Acronym
- PEACE
- Status last verified
- Mar 2023
- First submitted
- 3 Apr 2023
- Last updated
- 14 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An fMRI Investigation of the Effects of Selective Histamine-3 Receptor Antagonism on Cognitive and Emotional Processing in Healthy Individuals
- ClinicalTrials.gov ID
- NCT05849675
- Acronym / sponsor ID
- PEACE / PEACE
- Conditions
- Anhedonia, Cognitive Function
- Keywords
- Drug, fMRI, pharmaco-fMRI, Cognition, Histamine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 18 Feb 2024 (actual)
- Study completion
- 8 May 2024 (actual)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does pitolisant alter functional activity in brain regions linked to reward and cognitive processing during rest or cognitive task performance?
- 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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pitolisant | Experimental | Drug: Pitolisant 17.8 MG [Wakix]Two film-coated tablets (18mg x 2 [36mg]) for oral administration will be encapsulated in an opaque capsule. |
| Placebo | Placebo comparator | Drug: PlaceboTwo lactose film-coated tablets (2 x 65mg [125mg]) will be encapsulated in an opaque capsule (identical to the experimental arm drug). |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pitolisant 17.8 MG [Wakix]Single dose pitoliosant (36mg) | Drug | Pitolisant |
| PlaceboSingle dose placebo | Drug | Placebo |
Primary outcome
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
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
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
6 secondary outcomes
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.
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.
Accuracy of target selection on the Colour Change Detection Task
Time frame: 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 target selection during n-back fMRI 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
Time frame: 3-6 hours after single dose of drug or placebo.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2024.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susannah E Murphy, DPhil principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pitolisant 17.8 MG [Wakix] in people with Anhedonia and Cognitive Function, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
BOLD signal levels during resting state fMRI sequence (time frame: 3-6 hours after single dose of drug or placebo.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.