Clinical trial NCT05026398: Fenfluramine and Cognition
Official title: The Effect of Seven Day Fenfluramine Administration on Cognition in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cognitive Function
Keywords: Drug
Cognition
Dravet Syndrome
5-HT
Sigma-1
Healthy Volunteers
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
name: National Institute for Health Research, United Kingdom
First posted: 2021-08-30
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 22
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly allocated to one of two groups (fenfluramine or placebo), stratified on group allocation, gender and cognitive task version administered. Participants in the fenfluramine group will receive oral solution of fenfluramine 15mg twice daily (BID) for seven days. Participants in the placebo group will receive a placebo oral solution 15mg twice daily (BID) for seven days. The study is assessing the effects of fenfluramine on cognitive ability, it is not an efficacy or safety study.
Primary purpose: OTHER

Brief summary: In this study, the investigators will investigate the cognitive effects of fenfluramine, a drug that directly stimulates the release of serotonin in the brain and positively modulates σ1 function. The investigators will use fenfluramine to assess the cognitive effects of modulating serotonin and σ1 function in healthy volunteers using a battery of cognitive tasks that measure learning and memory, executive functioning, reward processing, and emotional processing. The study design is double-blind, and participants will be randomised to either seven days of fenfluramine or placebo administration. All participants will attend two screening visits to assess eligibility. There are two main study visits; during the first, participants will undertake cognitive tasks and questionnaires before taking the initial study dose. One the second study visit, participants will once again complete these tasks and questionnaires after a week of fenfluramine/placebo administration.


Eligibility criteria: Inclusion Criteria:

* Participant is willing and able to give informed consent for participation in the research
* Not currently taking any medications (except the contraceptive pill)
* Aged 18-22 years
* Male or female
* Sufficiently fluent English to understand and complete the task
* Body Mass Index above 18-30
* Weight of 40-75kg

Exclusion Criteria:

* Current pregnancy (as determined by urine pregnancy test taken during Screening and First Dose Visit) or breast feeding
* Any past or current Axis 1 DSM-V psychiatric disorder
* Clinically significant abnormal values for liver function tests, clinical chemistry, urine drug screen, blood pressure measurement 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, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurological conditions
* Current or past history of drug or alcohol dependency
* Current or past use of 3,4-Methylenedioxymethamphetamine (MDMA)
* 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)
* Participation in a study that involves the use of a medication within the last three months
* Smoking \> 5 cigarettes per day
* Typically drinks \> 6 caffeinated drinks per day (e.g. tea, coffee, coca cola, Red Bull)
* Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the Investigator

Primary outcomes:
measure: Change in Go/No-Go Task performance
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Change in Auditory Verbal Learning Task
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Change in N-back task performance
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary outcomes:
measure: Changes in reward sensitivity
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in categorisation of emotional words
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in recall of emotional words
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in recognition of emotional words
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in recognition of emotional facial expressions
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in visual short term memory on the Oxford Memory Test (OMT)
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in visual search ability
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
measure: Changes in control measures of subjective state
timeFrame: Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Department of Psychiatry, University of Oxford
Study officials:
affiliation: University of Oxford
name: Catherine J Harmer, DPhil
role: PRINCIPAL_INVESTIGATOR
References: