An Early Phase 1 interventional study of Losartan potassium and Placebo in Emotional Processing, sponsored by University of Oxford. Recruiting at 1 site in United Kingdom. Open to participants aged 16 Years to 20 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-06-15.
Sponsored by University of Oxford · Early Phase 1, Interventional, and Basic science
This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in young healthy volunteers.
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.
University of Oxford is the lead sponsor of 794 studies on the registry; 117 are open to participants now.
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Exclusion Criteria:
single-dose losartan potassium (Cozaar; weight-adjusted 25mg or 50mg)
Drug: Losartan potassium
Microcellulose placebo in identical capsule
Other: Placebo
Single dose losartan (25mg or 50 mg, weight-adjusted), encapsulated identically to placebo
Single tablet encapsulated identically to placebo
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
Time frame: 1 hour after capsule intake
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 1 hour after capsule intake
Plan to share: Undecided
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