- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05828940
Losartan and Memory
The Effect of Losartan on Emotion Regulation
Study Overview
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
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Oxford, United Kingdom, OX37JX
- Department of Psychiatry, University of Oxford
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
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-higher-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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
microcellulose
|
oral tablet, over-encapuslated
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Experimental: losartan
50mg losartan (Cozaar)
|
oral tablet, over-encapsulated
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
BOLD activation in hippocampus during new>familiar contrast
Time Frame: one hour after capsule intake
|
one hour after capsule intake
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
BOLD activation in other brain areas
Time Frame: one hour after capsule intake
|
one hour after capsule intake
|
pattern similarity
Time Frame: one hour after capsule intake
|
one hour after capsule intake
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Andrea Reinecke, PhD, Unoversity of Oxford
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- R58494/RE003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
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.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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