Losartan Effects on Emotion-memory Interaction

The Role of the Renin-angiotensin System in Emotion-memory Interactions

The purpose of this study is to investigate whether a single dose of losartan (50 mg) can affect emotion-memory interaction in healthy humans and its underlying neural mechanisms.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Losartan; Drug: Placebo Oral Tablet

Detailed Description

Animal models and initial findings in humans suggest a role of the renin-angiotensin system in cognitive and emotional processes. Accumulating evidence demonstrates modulatory effects of the angiotensin antagonist losartan in the domains of memory and emotional processing. Against this background the present study aims to investigate the behavioral and neural effects of a single dose of losartan on emotional processing and emotion-memory integration in healthy subjects. In a double-blind, between-subject, placebo-controlled pharmaco-fMRI experiment, 60 male participants will be randomized to a single dose of losartan (50 mg) or placebo, and encode emotional pictures during fMRI (scheduled 90 minutes after drug administration). Then 24 hours post fMRI participants will finish a surprise recognition memory test to estimate the emotion effects on subsequent memory.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 611731
      • Recruiting
      • University of Electronic Science and Technology of China
      • Contact: Weihua Zhao, PhD; Email: zarazhao.uestc@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Losartan group; Drug: Losartan	Drug: Losartan; administration of losartan (50 mg) (oral) Cozaar Oral Tablet; Other Names: Cozaar Oral Tablet
Placebo Comparator: Placebo group; Drug: Placebo Oral Tablet	Drug: Placebo Oral Tablet; administration of placebo (oral)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fMRI-based indices of neural activity during processing of emotional stimuli will be compared between the treatment groups	Neural activation during processing of emotional pictures will be assessed by functional magnetic resonance imaging (fMRI). The fMRI data will be analyzed by a Generalized Linear Model approach. Effects of treatment will be determined by comparing the losartan-treated group with the placebo-treated group.	120 to 150 minutes after treatment
fMRI-based indices of neural activity for subsequently successfully remembered as compared to non-remembered stimuli will be compared between the treatment groups	Neural activation for stimuli that are successfully remembered after an interval of 24hours will be compared to stimuli that are not successfully remembered. Neural activity between the subsequently remembered and non-remembered stimuli will be assessed by functional magnetic resonance imaging (fMRI) acquired during the initial encoding of the stimuli. The fMRI data will be analyzed by a Generalized Linear Model approach. Effects of treatment will be determined by comparing the losartan-treated group with the placebo-treated group.	120 to 150 minutes after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self-Assessment Manikin (SAM) ratings of arousal of the stimuli will be compared between the treatment groups	During the fMRI participants will rate the emotional arousal of each presented picture by means of the Self-Assessment Manikin (SAM). The assessment ranges from 1-5, with 1 referring to very low arousal while 5 refers to a very high arousal. The effects of treatment on arousal will be examined by comparing the losartan-treated with the placebo-treated group by means of a Generalized Linear Model approach.	120 to 150 minutes after treatment
Self-Assessment Manikin (SAM) ratings of valence of the stimuli will be compared between the treatment groups	During the fMRI participants will rate the emotional valence of each presented picture by means of the Self-Assessment Manikin (SAM). The assessment ranges from 1-5, with 1 referring to very negative valence, while 5 refers to a very positive valence. The effects of treatment on valence will be examined by comparing the losartan-treated with the placebo-treated group by means of a Generalized Linear Model approach.	120 to 150 minutes after treatment
Memory performance in terms of correctly recognized stimuli will be compared between the treatment groups	24 hours after the fMRI assessment subjects will be re-exposed to the stimuli that were presented during the fMRI and new stimuli. Subjects have to indicate for each stimulus whether it has been shown during fMRI. Memory performance in terms of correct responses will be computed and compared between the losartan-treated with the placebo-treated group by means of a Generalized Linear Model approach.	24 hours after treatment

Collaborators and Investigators

• Sponsor: University of Electronic Science and Technology of China
• Investigators: Principal Investigator: Benjamin Becker, PhD, University of Electronic Science and Technology of China

Publications and helpful links

General Publications

• Xu T, Zhou X, Jiao G, Zeng Y, Zhao W, Li J, Yu F, Zhou F, Yao S, Becker B. Angiotensin Antagonist Inhibits Preferential Negative Memory Encoding via Decreasing Hippocampus Activation and Its Coupling With the Amygdala. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022 Oct;7(10):970-978. doi: 10.1016/j.bpsc.2022.05.007. Epub 2022 May 30.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): March 31, 2022

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 21, 2020
• First Posted (Actual): October 28, 2020

Study Record Updates

• Last Update Posted (Actual): October 28, 2020
• Last Update Submitted That Met QC Criteria: October 21, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Losartan; Emotion-memory interaction
• 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: UESTC-neuSCAN-74

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No