search
Back to results

Serotonin-receptor Agonism in Reward Processing (SARP)

Primary Purpose

Anhedonia

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Buspirone 20mg
Placebo comparator
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Anhedonia focused on measuring 5HT1A receptor, Reward, Emotion, Memory, Buspirone

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Participant is willing and able to give informed consent for participation in the research
  • Male or female
  • Body mass index in the range of 18 to 30
  • Not currently taking any medications (except for contraception)

Exclusion Criteria:

  • • Any current Axis 1 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorder
  • Any previous episode of a severe mental illness,
  • A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia
  • Body Mass Index outside the range of 18 to 30 inclusive
  • Any significant current medical condition likely to interfere with conduct of the study or analysis of data (epilepsy, renal disease, hepatic disease, myasthenia gravis, acute closed-angle glaucoma)
  • Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion)
  • Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study
  • Currently pregnant or breast feeding
  • Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose
  • Participation in a study using the same tasks in the last year
  • Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging. This includes any taste/olfactory disturbance e.g. secondary to Covid-19 infection

Sites / Locations

  • Neurosciences building, Department of Psychiatry, Warneford hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Buspirone

Control

Arm Description

Outcomes

Primary Outcome Measures

Primary reward perception
Visual Analogue Scale of anticipation of pleasure, intensity of taste and pleasure experienced when tasting one of four 4 tastes representing a primary reward stimulus processing.
Effort based reward task:
offer acceptance based upon effort required (grip force on hand held dynamometer) to obtain outcome and success rate in expending correct amount of effort required for reward
Changes in reward sensitivity
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (Amount won, amount lost, total monetary amount earned , proportion of participants choosing the correct symbol in win and loss trials)

Secondary Outcome Measures

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.
Changes in categorisation of emotional words
Accuracy to categorise positive and negative descriptor words
Changes in recall of emotional words
Number of words accurately recalled
Change in N-back task performance
Accuracy on the N-back task
Change in Auditory Verbal Learning Task
Accuracy on AVLT (number of items recalled across blocks)
Cortisol measurement
Salivary cortisol measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Temperature measurement
Temperature measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Temporal Experience of Pleasure scale (TEPS)
Measure of anticipatory and consummatory aspects of reward (state measure). 18 item questionnaire (10 items for anticipatory; 8 items for consummatory). Each item scored on 6 point Likert scale (1 = very false for me to 6 = very true for me). Lower score indicates greater anhedonia.

Full Information

First Posted
March 24, 2022
Last Updated
May 9, 2023
Sponsor
University of Oxford
search

1. Study Identification

Unique Protocol Identification Number
NCT05357547
Brief Title
Serotonin-receptor Agonism in Reward Processing
Acronym
SARP
Official Title
Serotonin-receptor Agonism in Reward Processing
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
May 13, 2022 (Actual)
Primary Completion Date
April 18, 2023 (Actual)
Study Completion Date
April 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
There is growing animal and human evidence for role of 5HT1A receptor agonism in treating depression and reward deficits. The next step is to translate this evidence directly into humans by characterising the effects of buspirone, as a 5HT1A agonist, on cognitive models of reward and emotional processing. There is a paucity of behavioural evidence for the effect of 5HT1A receptor agonism, using buspirone as a probe, on primary reward processing (e.g. food), effort-based decision making or reward learning. Furthermore, the effects of 5HT1A agonism on non-emotive cognition, such as working memory, has yet to be investigated at a behavioural level in humans. This study will characterise the effects of buspirone, as a probe for 5HT1A receptor agonism, on reward processing in human cognitive models. Furthermore it will examine its role in emotional processing and working memory. This will add to the evidence base of the neurocognitive effects of 5HT1A receptor agonism in humans, which is of relevance to the development of this as a target for future treatment development. The study will be a double blinded, placebo controlled study involving healthy volunteers. Participants will receive a single dose of buspirone and then undergo a battery of psychometric testing to examine reward processing, emotional processing and a memory. Frequent monitoring of temperature and salivary cortisol shall be taken as surrogate markers of pre- and postsynaptic 5HT1A receptor activation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anhedonia
Keywords
5HT1A receptor, Reward, Emotion, Memory, Buspirone

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Buspirone
Arm Type
Experimental
Arm Title
Control
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Buspirone 20mg
Intervention Description
Buspirone tablets in opaque capsule. Used as probe for 5HT1A agonism
Intervention Type
Drug
Intervention Name(s)
Placebo comparator
Intervention Description
Lactose-sucrose tablets in opaque capsule
Primary Outcome Measure Information:
Title
Primary reward perception
Description
Visual Analogue Scale of anticipation of pleasure, intensity of taste and pleasure experienced when tasting one of four 4 tastes representing a primary reward stimulus processing.
Time Frame
On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))
Title
Effort based reward task:
Description
offer acceptance based upon effort required (grip force on hand held dynamometer) to obtain outcome and success rate in expending correct amount of effort required for reward
Time Frame
On day of intervention ( 90 - 180 minutes post intervention)
Title
Changes in reward sensitivity
Description
Sensitivity to reward as measured by the Probabilistic Instrumental Learning Task (Amount won, amount lost, total monetary amount earned , proportion of participants choosing the correct symbol in win and loss trials)
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Secondary Outcome Measure Information:
Title
Changes in recognition of emotional facial expressions
Description
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.
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Title
Changes in categorisation of emotional words
Description
Accuracy to categorise positive and negative descriptor words
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Title
Changes in recall of emotional words
Description
Number of words accurately recalled
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Title
Change in N-back task performance
Description
Accuracy on the N-back task
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Title
Change in Auditory Verbal Learning Task
Description
Accuracy on AVLT (number of items recalled across blocks)
Time Frame
On day of intervention (90 - 180 minutes post intervention)
Title
Cortisol measurement
Description
Salivary cortisol measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Time Frame
On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Title
Temperature measurement
Description
Temperature measurement at 30 minute intervals as surrogate of 5HT1A receptor activation
Time Frame
On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Title
Temporal Experience of Pleasure scale (TEPS)
Description
Measure of anticipatory and consummatory aspects of reward (state measure). 18 item questionnaire (10 items for anticipatory; 8 items for consummatory). Each item scored on 6 point Likert scale (1 = very false for me to 6 = very true for me). Lower score indicates greater anhedonia.
Time Frame
On screening day and testing day

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Participant is willing and able to give informed consent for participation in the research Male or female Body mass index in the range of 18 to 30 Not currently taking any medications (except for contraception) Exclusion Criteria: • Any current Axis 1 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) psychiatric disorder Any previous episode of a severe mental illness, A first degree relative diagnosed with Bipolar Affective Disorder Type 1 or Schizophrenia Body Mass Index outside the range of 18 to 30 inclusive Any significant current medical condition likely to interfere with conduct of the study or analysis of data (epilepsy, renal disease, hepatic disease, myasthenia gravis, acute closed-angle glaucoma) Current use of psychoactive and / or medically significant medication as judged by a study medic, whether prescribed or bought over the counter (the contraceptive pill, the Depo-Provera injection or the progesterone implant will not result in exclusion) Past history of dependence to illicit substances, and any consumption of illicit substances in the three months prior to the study Currently pregnant or breast feeding Known lactase deficiency or any other problem absorbing lactose, galactose, or glucose Participation in a study using the same tasks in the last year Any physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging. This includes any taste/olfactory disturbance e.g. secondary to Covid-19 infection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Harmer, DPhil
Organizational Affiliation
University of Oxford
Official's Role
Principal Investigator
Facility Information:
Facility Name
Neurosciences building, Department of Psychiatry, Warneford hospital
City
Oxford
State/Province
Oxfordshire
ZIP/Postal Code
OX3 7JX
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
An anonymised dataset will be published as open access data on a secure repository (e.g. Open Science Framework https://osf/io/).
IPD Sharing Time Frame
Indefinitely

Learn more about this trial

Serotonin-receptor Agonism in Reward Processing

We'll reach out to this number within 24 hrs