Fenfluramine and Cognition (FEN&Cognition)

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

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Function
• Intervention / Treatment: Drug: Fenfluramine; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Oxford, United Kingdom
    • Department of Psychiatry, University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 18 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenfluramine; Drug: Fenfluramine - 15mg twice daily oral solution for seven days	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 Names: Fintepla (trade name); Fenfluramine Hydrochloride (ZX008)
Placebo Comparator: Placebo; Placebo - 15mg twice daily oral solution for seven days	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
Changes in recall of emotional words	Number of words accurately recalled	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
Changes in recognition of emotional words	Number of words accurately recognised	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
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)
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)
Changes in visual search ability	Accuracy during contextual cueing task (CCT)	Immediately before initial dose (Day 1) and immediately before final visit (Day 7)
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)

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: National Institute for Health Research, United Kingdom; Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
• Investigators: Principal Investigator: Catherine J Harmer, DPhil, University of Oxford

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2021
• Primary Completion (Actual): June 22, 2022
• Study Completion (Actual): June 22, 2022

Study Registration Dates

• First Submitted: June 25, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 30, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Healthy Volunteers; Cognition; Sigma-1; Drug; Dravet Syndrome; 5-HT
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Fenfluramine
• Other Study ID Numbers: FenCog

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.
• IPD Sharing 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).
• IPD Sharing Access Criteria: The data will be made publicly available. Access requests will not be required.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes