Serotonin-receptor Agonism in Reward Processing

NCT05357547 | Completed Phase 2 DMC

• 1 other identifier: SARP01
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Anhedonia

Keywords

5HT1A receptor; Reward; Emotion; Memory; Buspirone

Outcome Measures

Primary Outcomes (3)

• 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.

  On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))

• 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

  On day of intervention ( 90 - 180 minutes post intervention)

• 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)

  On day of intervention (90 - 180 minutes post intervention)

Secondary Outcomes (8)

• Changes in recognition of emotional facial expressions

  On day of intervention (90 - 180 minutes post intervention)

• Changes in categorisation of emotional words

  On day of intervention (90 - 180 minutes post intervention)

• Changes in recall of emotional words

  On day of intervention (90 - 180 minutes post intervention)

• Change in N-back task performance

  On day of intervention (90 - 180 minutes post intervention)

• Change in Auditory Verbal Learning Task

  On day of intervention (90 - 180 minutes post intervention)

Study Arms (2)

Buspirone

EXPERIMENTAL

Drug: Buspirone 20mg

Control

PLACEBO COMPARATOR

Drug: Placebo comparator

Interventions

Buspirone 20mg DRUG

Buspirone tablets in opaque capsule. Used as probe for 5HT1A agonism

Buspirone

Placebo comparator DRUG

Lactose-sucrose tablets in opaque capsule

Control

Eligibility Criteria

• Age: 18 Years - 55 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
• Male or female
• Body mass index in the range of 18 to 30
• Not currently taking any medications (except for contraception)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Neurosciences building, Department of Psychiatry, Warneford hospital

Oxford, Oxfordshire, OX3 7JX, United Kingdom

Location

MeSH Terms

Conditions

Anhedonia

Interventions

Buspirone

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Polycyclic Compounds

Study Officials

• Catherine Harmer, DPhil

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2022
• First Posted: May 3, 2022
• Study Start: May 13, 2022
• Primary Completion: April 18, 2023
• Study Completion: April 18, 2023
• Last Updated: May 11, 2023

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Indefinitely

Locations

GB (1)