The Effects of Losartan on Reward Reinforcement Learning

Not Applicable

• Conditions: Healthy
• Interventions: Drug: Losartan; Drug: Placebo oral tablet

• Registration Number: NCT04604938
• Lead Sponsor: University of Electronic Science and Technology of China

Brief Summary

This study aims to investigate whether a single dose of losartan (50 mg) can affect learning from positive and negative outcomes and its related neural mechanisms.

Detailed Description

Emerging evidence suggests that the renin-angiotensin system can impact dopamine (DA) transmission and its modulatory role in reward processing. For instance, recent animal models have found that the angiotensin antagonist losartan reduces rewarding effects of methamphetamine and nicotine by modulating DA release in the striatum.The present study thus will investigate losartan effects on reward reinforcement learning and the underlying neural mechanisms. In a double-blind, between-subject, placebo-controlled design, 60 healthy male subjects will be randomly assigned to receive single-dose losartan (50 mg) or placebo, 90 minutes before performing a probabilistic reinforcement learning task during fMRI.

Study Timeline

• Status Verified: 2020-10
• Study First Submitted: 2020-10-09
• Study Start: 2020-10-10
• Study First Submitted QC: 2020-10-21
• Last Update Submitted: 2020-10-21
• Study First Posted: 2020-10-27
• Last Update Posted: 2020-10-27
• Primary Completion: 2021-12-31
• Study Completion: 2022-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 60

Inclusion Criteria

• Healthy subjects without past or current psychiatric or neurological disorders
• Right-handedness
• Normal or corrected-normal version

Exclusion Criteria

• History of head injury
• Medical or psychiatric illness
• Hypertension
• General cardio-vascular alteration or diseases
• Allergy against medications
• Visual or motor impairments
• Claustrophobia
• Drug addiction
• Nicotine dependence
• FMRI contradictions

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Losartan group	Losartan	Drug: Losartan
Placebo group	Placebo oral tablet	Drug: Placebo Oral Tablet

Primary Outcome Measures

Name	Time	Method
BOLD-level activity as assessed by fMRI during the learning phase	90 minutes to 110 minutes after treatment	During the paradigm subjects will learn the reward properties of stimuli via the presentation of trial-wise feedback. The neural activation during the prediction of positive and negative outcome feedback will be assessed by functional magnetic resonance imaging (fMRI), particularly in prefrontal and subcortical regions. The effects of treatment will be determined by comparing the losartan- and placebo-treated groups.
BOLD-level activity as assessed by fMRI during the learning transfer phase	111 minutes to 120 minutes after treatment	Following the initial learning phase subjects learning transfer will be examined by asking subjects to choose between stimuli with high versus low reward probabilities. The neural activation during correct responses will be assessed by functional magnetic resonance imaging (fMRI), particularly in prefrontal and subcortical regions. The effects of treatment will be determined by comparing the losartan- and placebo-treated groups.

Secondary Outcome Measures

Name	Time	Method
Learning rate for positive and negative outcomes	90 minutes to 110 minutes after treatment	The learning rate will be determined by performing computational modelling. The learning rate index for positive and negative outcomes during the learning phase will be compared between the losartan- and placebo-treated group.
Choice accuracy for the stimulus with the high reward probability during the learning phase	90 minutes to 110 minutes after treatment	During the learning phase accuracies (in percent) for choosing the stimulus with the highest reward probability will be computed. Effects of treatment on choice accuracy in the probabilistic learning task will be examined by comparing accuracies (percent) between the losartan- and placebo-treated group.
Choice accuracy during the learning transfer phase	111 minutes to 120 minutes after treatment	Following the initial learning phase subjects learning transfer will be examined by asking subjects to choose between stimuli with high versus low reward probabilities. For the transfer phase the choice accuracy for selecting stimuli with the highest reward probability and avoiding stimuli with the lowest reward probability will be computed. The effects of treatment will be determined by comparing the accuracy between the losartan- and placebo-treated groups.

Trial Locations

Locations (1)

University of Electronic Science and Technology of China; 🇨🇳 Chengdu, Sichuan, China