Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc. | INDUSTRY |
| National Institute for Health Research, United Kingdom | OTHER_GOV |
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fenfluramine | Experimental | Drug: Fenfluramine - 15mg twice daily oral solution for seven days |
|
| Placebo | Placebo Comparator | Placebo - 15mg twice daily oral solution for seven days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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) |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Catherine J Harmer, DPhil | University of Oxford | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Psychiatry, University of Oxford | Oxford | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39122687 | Derived | Colwell MJ, Tagomori H, Shang F, Cheng HI, Wigg CE, Browning M, Cowen PJ, Murphy SE, Harmer CJ. Direct serotonin release in humans shapes aversive learning and inhibition. Nat Commun. 2024 Aug 9;15(1):6617. doi: 10.1038/s41467-024-50394-x. |
Not provided
Not provided
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.
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).
The data will be made publicly available. Access requests will not be required.
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Jul 28, 2021 | Jul 28, 2021 | ICF_000.pdf |
Not provided
| ID | Term |
|---|---|
| D004831 | Epilepsies, Myoclonic |
| ID | Term |
|---|---|
| D004829 | Epilepsy, Generalized |
| D004827 | Epilepsy |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D005277 | Fenfluramine |
| ID | Term |
|---|---|
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
Not provided
Not provided
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.
Not provided
Not provided
Participant, Data Collectors, Outcomes Assessor
|
| 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 |
|
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) |
| D009422 |
| Nervous System Diseases |
| D000073376 | Epileptic Syndromes |