The Effects of Single-dose Losartan on Cognitive Flexibility and Learning in Healthy Adults: a Randomised Controlled Study
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Reinforcement Learning
研究概览
简要总结
This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in healthy volunteers.
详细描述
The renin-angiotensin system is a major hormone system involved in blood pressure regulation. However, its major receptors are also found in the brain, particularly in areas implicated in anxiety and depression. In line with this topography, drugs blocking angiotensin-II receptors have been shown to have effects on cognition that are opposite to those seen in emotional disorders. For instance, angiotensin receptor blockade improves fear extinction, and it dampens stress responsivity to highly aversive images. In line with such cognitive effects, population-based studies suggest that angiotensin receptor blockers - compared to other antihypertensive drugs - prevent the development of post-traumatic stress disorder following trauma exposition and improve outcomes in patients taking SSRI.
This study aims to shed further light on how the renin-angiotensin system affects different aspects of cognitive processing in humans relevant to emotional disorders. In a double-blind, randomized between-group design, we will investigate the effects of a single dose of losartan (50mg) versus placebo on emotional processing in N=60 healthy volunteers aged 18-50 years. Results from this study will help us understand how the renin-angiotensin system affects emotional processing in humans, and they will help us identify potential synergistic overlaps with the cognitive mechanisms of action of effective treatment of emotional disorders.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing and able to provide informed consent
- •Aged 18-50 years
- •Score of or below 45 on the Dimensional Anhedonia Rating Scale (DARS; Rizvi et al., 2015)
- •Sufficient written and spoken English skills to understand what the study involves, and to complete the questionnaires
- •Non- or light-smoker (5 cigarettes a day)
排除标准
- •Past or present DSM-5 axis-I diagnosis (based on SCID results at screening) other than anxiety disorder, dysthymia or unipolar depression
- •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
- •History of angioedema
- •Impaired kidney function (based on self-report)
- •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))
- •Lifetime history of epilepsy or other neurological disease (e.g. autism, ADHD)
- •Lifetime history of 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
- •Significant loss of hearing that is not corrected with a hearing device
- •Women: pregnancy, breast-feeding
研究组 & 干预措施
losartan
oral single-dose losartan potassium (Cozaar; 50mg)
干预措施: Losartan potassium 50mg (Drug)
placebo
Microcellulose placebo in identical capsule
干预措施: Placebo (Other)
结局指标
主要结局
Reinforcement Learning
时间窗: 1 hour after capsule intake
reinforcement learning, calculated as the learning rate from aversive and appetitive decision outcomes. Larger scores indicate better learning from an outcome.
次要结局
- Cognitive Flexibility(1 hour after capsule intake)
- AAT effect score(1hour after capsule intake)
- Motivational effort in the Apples Task(1hour after capsule intake)