Serotonin-receptor Agonism in Reward Processing

Anhedonia Clinical Trial

— SARP  

Official title:

Serotonin-receptor Agonism in Reward Processing

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05357547
• Other study ID #: SARP01
• Status: Completed
• Phase: Phase 2
• Start date: May 13, 2022
• Est. completion date: April 18, 2023

Study information

• Verified date: April 2022
• Source: University of Oxford
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: April 18, 2023
• Est. primary completion date: April 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Anhedonia

Intervention

Drug:
• Buspirone 20mg
Buspirone tablets in opaque capsule. Used as probe for 5HT1A agonism
• Placebo comparator
Lactose-sucrose tablets in opaque capsule

Locations

Country	Name	City	State
United Kingdom	Neurosciences building, Department of Psychiatry, Warneford hospital	Oxford	Oxfordshire

Sponsors (1)

Lead Sponsor	Collaborator
University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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))
Primary	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)
Primary	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	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.	On day of intervention (90 - 180 minutes post intervention)
Secondary	Changes in categorisation of emotional words	Accuracy to categorise positive and negative descriptor words	On day of intervention (90 - 180 minutes post intervention)
Secondary	Changes in recall of emotional words	Number of words accurately recalled	On day of intervention (90 - 180 minutes post intervention)
Secondary	Change in N-back task performance	Accuracy on the N-back task	On day of intervention (90 - 180 minutes post intervention)
Secondary	Change in Auditory Verbal Learning Task	Accuracy on AVLT (number of items recalled across blocks)	On day of intervention (90 - 180 minutes post intervention)
Secondary	Cortisol measurement	Salivary cortisol measurement at 30 minute intervals as surrogate of 5HT1A receptor activation	On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Secondary	Temperature measurement	Temperature measurement at 30 minute intervals as surrogate of 5HT1A receptor activation	On day of intervention (30 minutes pre-intervention, at time of intervention, at 30 minute intervals thereafter)
Secondary	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.	On screening day and testing day