Fenfluramine and Cognition

NCT05026398 | Completed Phase 4 FDA Drug

• 1 other identifier: FenCog
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Function

Keywords

Drug; Cognition; Dravet Syndrome; 5-HT; Sigma-1; Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (8)

• Changes in reward sensitivity

  Immediately before initial dose (Day 1) and immediately before final visit (Day 7)

• Changes in categorisation of emotional words

  Immediately before initial dose (Day 1) and immediately before final visit (Day 7)

• Changes in recall of emotional words

  Immediately before initial dose (Day 1) and immediately before final visit (Day 7)

• Changes in recognition of emotional words

  Immediately before initial dose (Day 1) and immediately before final visit (Day 7)

• Changes in recognition of emotional facial expressions

  Immediately before initial dose (Day 1) and immediately before final visit (Day 7)

Study Arms (2)

Fenfluramine

EXPERIMENTAL

Drug: Fenfluramine - 15mg twice daily oral solution for seven days

Drug: Fenfluramine

Placebo

PLACEBO COMPARATOR

Placebo - 15mg twice daily oral solution for seven days

Other: Placebo

Interventions

Fenfluramine DRUG

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.

Also known as: Fintepla (trade name), Fenfluramine Hydrochloride (ZX008)

Fenfluramine

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 22 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 (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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Oxford: lead
• Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

Department of Psychiatry, University of Oxford

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Epilepsies, Myoclonic

Interventions

Fenfluramine

Condition Hierarchy (Ancestors)

Epilepsy, Generalized; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Catherine J Harmer, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participant, Data Collectors, Outcomes Assessor
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof Catherine Harmer

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: August 30, 2021
• Study Start: April 12, 2021
• Primary Completion: June 22, 2022
• Study Completion: June 22, 2022
• Last Updated: November 15, 2022

Record last verified: 2022-11

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 Jan 2022), unblinding has occurred (ETA Feb 2022), and all data analyses has been completed (ETA June 2022).
• Access Criteria: The data will be made publicly available. Access requests will not be required.

Locations

GB (1)