Losartan and Social Processing

Early Phase 1RecruitingNCT06624904

University of Oxford68 enrolled

Overview

This study explores the effects of single-dose losartan (50mg) versus placebo on social processing in healthy volunteers.

While renin-angiotensin mechanisms have been implicated in physiological disease, such as hypertension and stroke, the discovery of a local brain renin-angiotensin system (RAS) in the 1970s brought into question whether the RAS may play a role in psychiatric disorders too. Recent work has supported this link, with several studies reporting RAS influence on aversive learning, stress response to traumatic stimuli, and fear extinction. Despite these promising results, studies have yet to fully explore the influence of the RAS and losartan on social processes. It is plausible that the RAS may be involved in social functioning, as recent work reported that losartan reduces sensitivity to social punishment in healthy volunteers. Such an effect of losartan may have broad relevance for psychopathology, as impairment to social functioning is present across a range of psychiatric disorders. In this double-blind, randomized between-group study, the investigators will examine the effects of a single dose of losartan (50mg) versus placebo on social processing in N=68 healthy volunteers. Following a one-hour waiting period, participants will complete a set of computer tasks investigating social processes reported to be sensitive to psychopathology. Specifically, participants will complete the Approach Avoidance Task which assesses social approach and avoidance behaviour in response to various facial expressions via joystick movement, the Interpretation Inflexibility Task which evaluates cognitive flexibility in a social context, the Social Learning Trust Game which evaluates social learning through a trust game between participant investors and realistic trustees, and Cyberball, which probes response to social rejection. Results from this study will provide more insight on the potential role of the RAS in social cognitive processing in humans, which could lead to an improved mechanistic understanding of emotional disorders that are marked by social impairment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Social Cognition

Interventions

Losartan potassium 50mgDRUG

Single dose losartan (50 mg), encapsulated identically to placebo.

PlaceboOTHER

Single tablet encapsulated identically to placebo.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Willing and able to provide informed consent * Aged 18-50 years * Sufficient written and spoken English skills to understand what the study involves, and to complete the questionnaires * Non- or light-smoker (5 cigarettes a day, if vaping: less than 50 puffs) * BMI between 18 - 30 Exclusion Criteria: * Current DSM-5 axis-I diagnosis (based on SCID results at screening) or history of a severe psychological disorder such as psychotic disorder, bipolar disorder, alcohol or substance abuse, or post-traumatic stress disorder * First-degree family member with severe psychiatric illness (including psychosis, bipolar disorder, unipolar psychotic depression). * CNS-medication last 6 weeks (including as part of another study) * Current blood pressure or other heart medication, including aliskiren and beta blockers) * Diagnosis of intravascular fluid depletion or dehydration * History of angioedema * Impaired kidney function (based on self-report) * Very low blood pressure (defined as repeated (at least three consecutive measurements) measures of blood pressure under standardised conditions where either the systolic or the diastolic blood pressure or both are below 90/50 mmHg (in accordance with established standard definitions) * Lifetime history of epilepsy or other neurological disorder, as established by a professional diagnosis (e.g. autism, ADHD) * Lifetime history of systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study * Significant loss of hearing that is not corrected with a hearing device * Women: pregnancy (as determined by a urine test, if the participant's pregnancy status is unknown during the in-person visit), breast-feeding

Locations (1)

Warneford Hospital

Oxford, Oxfordshire, United Kingdom

RECRUITING

Outcomes

Primary Outcomes

AAT effect score

mean reaction time of the pull trials of a valence category subtracted from the push trials of the same category, yielding a single indicator of approach/avoidance, with positive scores indicating relatively stronger approach and negative scores indicating relatively stronger avoidance

Time frame: 1 hour after capsule intake

Secondary Outcomes

Sensitivity to Social Rejection

a) feelings of belonging, control, self-esteem, meaningful existence (on a scale from 1 to 5, with some items reverse coded) as measured on the reflexive and reflective needs-threat scale following Cyberball.

Time frame: 1 hour after capsule intake

Social Learning

Social learning rate (early round versus late round investment decisions by generosity condition)

Time frame: 1 hour after capsule intake

Interpretation Inflexibility

Within-person revision of biased interpretations: calculated by taking the average of differences between bias scores between stage 3/2 and 2/1. These two differences will be squared before averaging to reflect absolute change (i.e., in either direction), then the square root of the resulting average will be taken. Higher values mean more flexibility in revising prior interpretations.

Time frame: 1 hour after capsule intake

Central Contacts

Andrea Reinecke, PhD

CONTACT

01865 618320 andrea.reinecke@psych.ox.ac.uk

Divya Prasad, MSc

CONTACT

divya.prasad@psych.ox.ac.uk

Data from ClinicalTrials.gov

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