Clinical trial NCT05357547: Serotonin-receptor Agonism in Reward Processing
Official title: Serotonin-receptor Agonism in Reward Processing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anhedonia
Keywords: 5HT1A receptor
Reward
Emotion
Memory
Buspirone
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2022-05-03
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Primary reward perception
timeFrame: On day of intervention (30 minutes pre-intervention and post-intervention (60 - 180 minutes))
measure: Effort based reward task:
timeFrame: On day of intervention ( 90 - 180 minutes post intervention)
measure: Changes in reward sensitivity
timeFrame: On day of intervention (90 - 180 minutes post intervention)
Secondary outcomes:
measure: Changes in recognition of emotional facial expressions
timeFrame: On day of intervention (90 - 180 minutes post intervention)
measure: Changes in categorisation of emotional words
timeFrame: On day of intervention (90 - 180 minutes post intervention)
measure: Changes in recall of emotional words
timeFrame: On day of intervention (90 - 180 minutes post intervention)
measure: Change in N-back task performance
timeFrame: On day of intervention (90 - 180 minutes post intervention)
measure: Change in Auditory Verbal Learning Task
timeFrame: On day of intervention (90 - 180 minutes post intervention)
measure: Cortisol measurement
timeFrame: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
measure: Temperature measurement
timeFrame: On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
measure: Temporal Experience of Pleasure scale (TEPS)
timeFrame: On screening day and testing day
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: Neurosciences building, Department of Psychiatry, Warneford hospital
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Catherine Harmer, DPhil
role: PRINCIPAL_INVESTIGATOR
References: