Fenfluramine and Cognition

Cognitive Function Clinical Trial

— FEN&Cognition  

Official title:

The Effect of Seven Day Fenfluramine Administration on Cognition in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05026398
• Other study ID #: FenCog
• Status: Completed
• Phase: Phase 4
• Start date: April 12, 2021
• Est. completion date: June 22, 2022

Study information

• Verified date: November 2022
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: June 22, 2022
• Est. primary completion date: June 22, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 22 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Function

Intervention

Drug:
• Fenfluramine
Fenfluramine (30mg daily) will be dispensed in a cherry flavoured aqueous solution. Fenfluramine is both a serotonin releasing agent and sigma-1 receptor agonist. Fenfluramine is FDA approved for the treatment of Dravet syndrome, a rare form of epilepsy.

Other:
• Placebo
The placebo is a liquid designed to be identical to the interventional drug fenfluramine in terms of both taste and visual appearance. It will be administered at 30mg daily and dispensed in a cherry flavoured aqueous solution

Locations

Country	Name	City	State
United Kingdom	Department of Psychiatry, University of Oxford	Oxford

Sponsors (3)

Lead Sponsor	Collaborator
University of Oxford	National Institute for Health Research, United Kingdom, Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Go/No-Go Task performance	Accuracy on the Go/No-Go task	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Primary	Change in Auditory Verbal Learning Task	Accuracy on AVLT (number of items recalled across blocks)	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Primary	Change in N-back task performance	Accuracy on the N-back task	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in reward sensitivity	Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (PILT)	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in categorisation of emotional words	Accuracy to categorise positive and negative descriptor words	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in recall of emotional words	Number of words accurately recalled	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in recognition of emotional words	Number of words accurately recognised	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in recognition of emotional facial expressions	Accuracy of emotion labels (e.g. disgusted face) assigned by participants to expressive faces which have appeared on a computer screen for a period of 500ms.	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in visual short term memory on the Oxford Memory Test (OMT)	Accuracy on the Oxford Memory Task	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in visual search ability	Accuracy during contextual cueing task (CCT)	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Secondary	Changes in control measures of subjective state	Ratings on the Positive and Negative Affect Schedule	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)