Losartan and Social Processing

The Effects of Single-dose Losartan on Social Processing in Healthy Adults: a Randomized Controlled Study

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

Study Overview

• Status: Recruiting
• Conditions: Social Cognition
• Intervention / Treatment: Drug: Losartan potassium 50mg; Other: Placebo

Detailed Description

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
• Enrollment (Estimated): 68
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Andrea Reinecke, PhD; Phone Number: 01865 618320; Email: andrea.reinecke@psych.ox.ac.uk
• Study Contact Backup: Name: Divya Prasad, MSc; Email: divya.prasad@psych.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX37JX
      • Recruiting
      • Warneford Hospital
      • Contact: Andrea Reinecke, PhD; Phone Number: 01865 618320; Email: andrea.reinecke@psych.ox.ac.uk
      • Principal Investigator: Andrea Reinecke, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan; 50 mg single-dose losartan	Drug: Losartan potassium 50mg; Single dose losartan (50 mg), encapsulated identically to placebo.; Other Names: Cozaar; Losartan
Placebo Comparator: Placebo; Microcellulose placebo in identical capsule	Other: Placebo; Single tablet encapsulated identically to placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 hour after capsule intake

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 hour after capsule intake
Social Learning	Social learning rate (early round versus late round investment decisions by generosity condition)	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.	1 hour after capsule intake

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Oxford Health Biomedical Research Centre (OH BRC) support scheme

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 23, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Losartan; Renin Angiotensin System; Social Processing
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: R92661

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• 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