The Effect of Losartan on Emotional Processing in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT03434054
• Recruitment Status: Completed
• First Posted: February 15, 2018
• Last Update Posted: February 19, 2018
• Sponsor: University of Oxford
• Information provided by (Responsible Party): University of Oxford

Study Description

Brief Summary:

This experimental medicine study explores whether a single dose of losartan (50mg) versus placebo affects the processing of positive and negative stimuli, using fMRI.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: Losartan; Other: Placebo	Not Applicable

Detailed Description:

Losartan has been shown to accelerate fear extinction in animals and to prevent the development of anxiety disorders in humans, emphasising its potential to possibly enhance exposure therapy in humans. This study explores the basic effects of losartan on emotional processing, to identify neural mechanisms by which the drug might have synergistic effects on psychological treatment in humans.

In a double-blind between-groups design, 30 healthy volunteers will be randomised to a group receiving a single dose of losartan (50mg) versus placebo, and this study will measure the effects of probing renin-angiotensin function on emotional information processing, using functional magnet resonance imaging (fMRI). Such knowledge will ultimately be essential for the development of more effective pharmaco-psychological treatment approaches for anxiety disorders.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a double-blind, placebo-controlled experimental medicine study, where healthy volunteers are randomised to receiving either a single dose of losartan (50mg) or matching placebo.
• Masking: Double (Participant, Investigator)
• Masking Description: Study medication and placebo are over-encapsulated to look identical, and both the participants and investigators in direct contact with partiicpants are blind to group allocation.
• Primary Purpose: Basic Science
• Official Title: The Effect of Losartan on Emotional Processing in Healthy Volunteers
• Actual Study Start Date: June 1, 2016
• Actual Primary Completion Date: June 30, 2017
• Actual Study Completion Date: June 30, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Losartan; single dose of 50mg losartan, tablet, over-encapsulated, to be taken orally	Drug: Losartan; blood pressure medication; Other Name: Losartan Potassium
Placebo Comparator: Placebo; single dose of placebo (main ingredient microcrystalline cellulose), tablet, over-encapsulated, to be taken orally	Other: Placebo; non-active sham intervention

Outcome Measures

Primary Outcome Measures :

1. BOLD signal change [ Time Frame: 1 day ]
   BOLD signal change during functional magnet resonance imaging (fMRI)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• willing and able to provide informed consent
• male or Female, aged 18-50
• body mass index (BMI) of 18-30 kg/m2
• fluent English skills
• non- or light-smoker (< 5 cigarettes a day)

Exclusion Criteria:

• Female participant who is pregnant or breast-feeding
• central nervous system (CNS) active medication during the last 6 weeks
• Current blood pressure/other heart medication (esp. aliskiren or beta blockers)
• Intravascular fluid depletion
• Past or present DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) axis-I diagnosis
• Alcohol or substance abuse
• First-degree family member with a history of a severe psychiatric disease
• Impaired liver or kidney function
• Lifetime history of epilepsy or other neurological disease, 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.
• Insufficient English skills
• participated in another study involving certain medication during last 6 weeks
• Contraindication to magnet resonance imaging (MRI) scanning (e.g. pacemaker)

Contacts and Locations

Sponsors and Collaborators

University of Oxford

Investigators

• Study Chair: Andrea Reinecke, PhD; University of Oxford

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Reinecke A, Browning M, Klein Breteler J, Kappelmann N, Ressler KJ, Harmer CJ, Craske MG. Angiotensin Regulation of Amygdala Response to Threat in High-Trait-Anxiety Individuals. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018 Oct;3(10):826-835. doi: 10.1016/j.bpsc.2018.05.007. Epub 2018 Jun 5.

• Responsible Party: University of Oxford
• ClinicalTrials.gov Identifier: NCT03434054
• Other Study ID Numbers: MSD-IDREC-C3-2015-832
• First Posted: February 15, 2018
• Last Update Posted: February 19, 2018
• Last Verified: February 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Oxford:

losartan; emotional processing; anxiety; magnet resonance imaging; MRI

Additional relevant MeSH terms:

Losartan; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action