Emotional ProcessingEarly Phase 1NCT06636812
Losartan and Emotional Processing in Young People
A Early Phase 1 study testing Losartan potassium in people with Emotional Processing, run by University of Oxford at 1 site in United Kingdom.
Trial summary
This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in young healthy volunteers. Read more about this study
- Who is it for?
- Ages 16 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Emotional Processing
- What is being tested?
- Losartan potassium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 Mar 2024to 31 Dec 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Willing and able to provide informed consent (for 16 and 17 year olds: assent and parental/ legal guardian consent)
- Non- or light-smoker (\< 5 cigarettes a day)
- Ability to attend appointments in Oxford with reasonable travel costs
- Ability/ willingness to provide GP contact details
Who cannot join
- Past or present DSM-5 axis-I diagnosis (based on SCID results at screening), especially severe psychiatric illness or alcohol or substance dependence
- First-degree family member with severe psychiatric illness
- CNS-medication last 6 weeks (including as part of another study)
- Current blood pressure or other heart medication (especially aliskiren or beta blockers)
- Diagnosis of intravascular fluid depletion or dehydration
- Impaired kidney function (based on blood test at screening, cut-off 75 ml/min/1.73 m2)
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- Significant hyperkalaemia (level\>=6mEq/L in the absence of sample haemolysis will be considered significant hyperkalaemia)
- Very low blood pressure (defined as repeated (at least three consecutive measurements) measures of blood pressure under standardised conditions where either the systolic or the diastolic blood pressure or both are below 90/50 mmHg (in accordance with established standard definitions: DOI 10.1186/s12887-016-0633-7))
- Body weight below 35kg (as the lower dose of 25mg of losartan only indicated from 35kg)
- Lifetime history of epilepsy or other neurological disease (e.g. ADHD, autism)
- Lifetime history of angioedema, renal artery stenosis, valvular heart disease, recurrent postural/ orthostatic hypotension
- Lifetime history ofsystemic 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.
- Significant loss of hearing that is not corrected with a hearing device Insufficient written and/or spoken English skills
- Women: pregnancy, breast-feeding
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Warneford Hospital, University of Oxford
Oxford, Oxfordshire, OX37JX
Andrea Reinecke, PhD, 01865 618320, andrea.reinecke@psych.ox.ac.uk
Andrea Reinecke, PhD
About this study
Official title: The Effects of Single-dose Losartan on the Processing of Emotional Information in Healthy Adolescents: a Randomised Controlled Study
This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in young healthy volunteers.
Read the detailed description
Compared to children and adults, adolescents are most likely to develop an anxiety disorder and less likely to respond to even the most effective treatment - exposure therapy. Similarly, fear extinction - the laboratory equivalent to exposure therapy - is impaired in this young age group. Animal and human research suggests that such deficits in fear reduction may be underpinned by insufficient functioning of the ventromedial prefrontal cortex (vmPFC) during adolescence as part of normative development.
A single dose of losartan, a commonly prescribed blood pressure drug targeting the renin-angiotensin system, has been shown to enhance fear extinction in adult humans (Zhou et al. 2019). Most importantly, such effects are seen to be driven by improved vmPFC function following losartan (Zhou et al. 2019). Our own work in adults has also demonstrated rapid beneficial effects of single-dose losartan on other neurocognitive markers relevant to anxiety and treatment response, while not revealing any adverse reactions (Reinecke et al., 2018; Pulcu et al., 2019; Shkreli et al., 2020). These findings suggest that the renin-angiotensin system plays a key role in the extinction of anxiety, and that adding losartan to exposure therapy for anxiety in humans might have synergistic effects.
In this double-blind, randomized between-group study, we will investigate the effects of a single dose of losartan (weight-adjusted: 50mg if over/ 25mg if below 50kg) versus placebo on emotional processing in N=60 healthy volunteers aged 16-20 years. One hour later, when drug-peak plasma levels are reached, participants will work on a battery of computerized tasks, including a fear extinction task and other tasks exploring attention for and learning from neutral and emotional stimuli of differing valence. Results from this study will help us understand how the renin-angiotensin system affects emotional processing in human adolescents, and they will help us identify potential synergistic overlaps with the cognitive mechanisms of effective exposure therapy.
- Conditions
- Emotional Processing
- Being tested
- Losartan potassium, Placebo
- Keywords
- emotional processing, anxiety, adolescents
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losartan potassiumDrug
Single dose losartan (25mg or 50 mg, weight-adjusted), encapsulated identically to placebo
PlaceboOther
Single tablet encapsulated identically to placebo
| Study group | Role | What they receive |
|---|---|---|
| losartan | Experimental | single-dose losartan potassium (Cozaar; weight-adjusted 25mg or 50mg) Receives: Drug: Losartan potassium |
| Placebo | Placebo comparator | Microcellulose placebo in identical capsule Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fear Extinction
fear extinction score, computed as a 5-point Likert scale valence rating (1=unpleasant-5=pleasant) of the CS+ stimulus at the end of extinction minus at the end of acquisition, with larger scores indicating better fear extinction
Measured: 1 hour after capsule intake
Secondary outcomes (4)
Pattern Separation
Lure discrimination index (LDI), calculated as the rate of 'similar' responses to lures minus 'similar' responses to foils, with higher scores indicating better mnemonic discrimination
Measured: 1 hour after capsule intake
Cognitive Flexibility
switch cost, calculated by rank-ordering the differences between each switch trial RT and each participants average RT for all non-switch trials from 1 - 10 (with better and worse bins having values closer to 1 and 10, respectively), and then summing the bin values to compute a total bin score for each participant. Inaccurate responses are penalized by being assigned a score of 20. Smaller bin scores indicate greater accuracy and lower RT.
Measured: 1 hour after capsule intake
Reinforcement Learning
reinforcement learning, calculated as the learning rate from aversive and appetitive decision outcomes. Larger scores indicate better learning from an outcome.
Measured: 1 hour after capsule intake
Faces Dot Probe Task
extradecisional threat bias, calculated by subtracting the extradecisional time parameter for congruent trials from the extradecisional time parameter for incongruent trials. Larger scores indicate a greater degree of vigilance to threat.
Measured: 1 hour after capsule intake
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start7 Mar 2024
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Emotional ProcessingStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel randomised experimental medicine trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Responsible party
- Sponsor
- Investigators
- Andrea Reinecke, PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06636812
- Sponsor's protocol ID
- R79545
- Status last verified
- Sep 2024
- First submitted
- 23 Sep 2024
- Last updated
- 15 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Single-dose Losartan on the Processing of Emotional Information in Healthy Adolescents: a Randomised Controlled Study
- ClinicalTrials.gov ID
- NCT06636812
- Acronym / sponsor ID
- R79545
- Conditions
- Emotional Processing
- Keywords
- emotional processing, anxiety, adolescents
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom
- Study start
- 7 Mar 2024 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 15 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in young healthy volunteers.
Detailed description
Compared to children and adults, adolescents are most likely to develop an anxiety disorder and less likely to respond to even the most effective treatment - exposure therapy. Similarly, fear extinction - the laboratory equivalent to exposure therapy - is impaired in this young age group. Animal and human research suggests that such deficits in fear reduction may be underpinned by insufficient functioning of the ventromedial prefrontal cortex (vmPFC) during adolescence as part of normative development.
A single dose of losartan, a commonly prescribed blood pressure drug targeting the renin-angiotensin system, has been shown to enhance fear extinction in adult humans (Zhou et al. 2019). Most importantly, such effects are seen to be driven by improved vmPFC function following losartan (Zhou et al. 2019). Our own work in adults has also demonstrated rapid beneficial effects of single-dose losartan on other neurocognitive markers relevant to anxiety and treatment response, while not revealing any adverse reactions (Reinecke et al., 2018; Pulcu et al., 2019; Shkreli et al., 2020). These findings suggest that the renin-angiotensin system plays a key role in the extinction of anxiety, and that adding losartan to exposure therapy for anxiety in humans might have synergistic effects.
In this double-blind, randomized between-group study, we will investigate the effects of a single dose of losartan (weight-adjusted: 50mg if over/ 25mg if below 50kg) versus placebo on emotional processing in N=60 healthy volunteers aged 16-20 years. One hour later, when drug-peak plasma levels are reached, participants will work on a battery of computerized tasks, including a fear extinction task and other tasks exploring attention for and learning from neutral and emotional stimuli of differing valence. Results from this study will help us understand how the renin-angiotensin system affects emotional processing in human adolescents, and they will help us identify potential synergistic overlaps with the cognitive mechanisms of effective exposure therapy.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel randomised experimental medicine trial
| Arm | Type | Receives |
|---|---|---|
| losartan | Experimental | Drug: Losartan potassiumsingle-dose losartan potassium (Cozaar; weight-adjusted 25mg or 50mg) |
| Placebo | Placebo comparator | Other: PlaceboMicrocellulose placebo in identical capsule |
Who may qualify
- Ages
- 16 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Willing and able to provide informed consent (for 16 and 17 year olds: assent and parental/ legal guardian consent)
- Non- or light-smoker (\< 5 cigarettes a day)
- Ability to attend appointments in Oxford with reasonable travel costs
- Ability/ willingness to provide GP contact details
Key exclusion criteria (14 listed)
- Past or present DSM-5 axis-I diagnosis (based on SCID results at screening), especially severe psychiatric illness or alcohol or substance dependence
- First-degree family member with severe psychiatric illness
- CNS-medication last 6 weeks (including as part of another study)
- Current blood pressure or other heart medication (especially aliskiren or beta blockers)
- Diagnosis of intravascular fluid depletion or dehydration
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Losartan potassiumSingle dose losartan (25mg or 50 mg, weight-adjusted), encapsulated identically to placebo | Drug | losartan |
| PlaceboSingle tablet encapsulated identically to placebo | Other | Placebo |
Primary outcome
Fear Extinction
Time frame: 1 hour after capsule intake
fear extinction score, computed as a 5-point Likert scale valence rating (1=unpleasant-5=pleasant) of the CS+ stimulus at the end of extinction minus at the end of acquisition, with larger scores indicating better fear extinction
4 secondary outcomes
Pattern Separation
Time frame: 1 hour after capsule intake
Cognitive Flexibility
Time frame: 1 hour after capsule intake
Reinforcement Learning
Time frame: 1 hour after capsule intake
Faces Dot Probe Task
Time frame: 1 hour after capsule intake
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrea Reinecke, PhD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Losartan potassium in people with Emotional Processing, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Andrea Reinecke, PhD (+44 01865 618320, andrea.reinecke@psych.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fear Extinction (time frame: 1 hour after capsule intake). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2025.