Losartan and Memory

Sponsor

University of Oxford (Other)

Overall Status

Completed

CT.gov ID

NCT05828940

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study investigates the effect of a single dose of 50mg losartan vs placebo on BOLD signal during memory encoding.

Condition or Disease	Intervention/Treatment	Phase
PTSD	Drug: Losartan Potassium Drug: Placebo	N/A

Detailed Description

The commonly prescribed antihypertensive drug losartan targets the renin-angiotensin system - a hormone system regulating blood pressure - by acting as an angiotensin receptor antagonist. The drug prevents a docking of the protein angiotensin IV to AT1 receptors, which leads to a dilation if vessels and a reduction in blood pressure. However, the increase in free angiotensin IV has also been associated with an increase in synaptic plasticity, the cellular mechanism involved in learning and memory. As such, losartan appears to have cognition-enhancing properties, in a way that a single dose of 50mg improves prospective memory in healthy humans . However, preliminary pre-clinical results also suggest that a single injection of the drug improves fear extinction in rodents, which is the equivalent to human cognitive-behavioural therapy for anxiety disorders . Furthermore, compared to other antihypertensive drugs, regular losartan treatment appears to prevent the development of post-traumatic stress disorder following trauma exposition . Such results suggest that the renin-angiotensin system may play a key role in the prevention of anxiety.

In this study, we investigate the effect kof probing the renin-angiotensin system on memory encoding, which has previously been shown to be impaired in PTSD. In a double-blind, randomised between-groups design, 40 healthy volunteers with moderate to high levels of trait anxiety are randomised to a group receiving a single dose of losartan (50mg) versus placebo. When peak plasma levels are reached, participants work on a battery of behavioural and neural measures of emotional information processing. These tasks will include an fMRI task where participants will see images of animals and landscapes on the screen and categorise these accordingly, to be tested for memory for these images in a later task.

The results from this study will help us understand how the renin-angiotensin system affects memory formation, and they will help us establish a battery of tasks that sensitively respond to such manipulations. Such information will ultimately lead to the development of losartan and similar agents for the more effective and more compact treatment of anxiety disorders.

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomised double-blindrandomised double-blind

Masking:

Double (Participant, Investigator)

Masking Description:

double-blind

Primary Purpose:

Basic Science

Official Title:

The Effect of Losartan on Emotion Regulation

Actual Study Start Date :

Oct 1, 2019

Actual Primary Completion Date :

Mar 31, 2022

Actual Study Completion Date :

Mar 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: placebo microcellulose	Drug: Placebo oral tablet, over-encapuslated
Experimental: losartan 50mg losartan (Cozaar)	Drug: Losartan Potassium oral tablet, over-encapsulated

Arm

Intervention/Treatment

Placebo Comparator: placebo

microcellulose

Drug: Placebo

oral tablet, over-encapuslated

Experimental: losartan

50mg losartan (Cozaar)

Drug: Losartan Potassium

oral tablet, over-encapsulated

Outcome Measures

Primary Outcome Measures

BOLD activation in hippocampus during new>familiar contrast [one hour after capsule intake]

Secondary Outcome Measures

BOLD activation in other brain areas [one hour after capsule intake]
pattern similarity [one hour after capsule intake]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

willing and able to provide informed consent
male or Female, aged 18-50 years
body mass index (BMI) of 18-30 kg/m2
non- or light-smoker (< 5 cigarettes a day)
STAIT score of at least 40

Exclusion Criteria:

Female participant who is pregnant or breast-feeding
CNS-active medication during the last 6 weeks
Current blood pressure or other heart medication (especially aliskiren or beta blockers)
Diagnosis of intravascular fluid depletion or dehydration
Past or present DSM-IV axis-I diagnosis or suspected diagnosis (from SCID results at screening)
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.
High or moderate risk of coronavirus, based on the NHS checklist for coronavirus vulnerability https://www.nhs.uk/conditions/coronavirus-covid-19/people-at-higher-risk/whos-at-highe r-risk-from-coronavirus/
Contraindication to MRI (e.g. metal implant)
Insufficient English skills
participated in another study involving CNS-active medication during the last 6 weeks Participants will also not be able to take part if they are left-handed, due to the research MRI aspect of the study relying on group means.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Psychiatry, University of Oxford	Oxford		United Kingdom	OX37JX

Sponsors and Collaborators

University of Oxford

Investigators

Principal Investigator: Andrea Reinecke, PhD, Unoversity of Oxford

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

University of Oxford

ClinicalTrials.gov Identifier:

NCT05828940

Other Study ID Numbers:

R58494/RE003

First Posted:

Apr 25, 2023

Last Update Posted:

Apr 27, 2023

Last Verified:

Apr 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Losartan

Study Results

No Results Posted as of Apr 27, 2023