Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers (Protocol 3)
- Conditions
- Vascular DiseaseHeart Disease
- Interventions
- Registration Number
- NCT01096706
- Lead Sponsor
- University of Edinburgh
- Brief Summary
Impairment of the heart's pumping capacity (heart failure) remains a major clinical problem with a poor prognosis and the search for novel treatments remains an important area of research.
Urocortins are proteins that appear to increase blood flow and heart pumping activity. There has been particular interest in the role of Urocortins 2 \& 3 (subtypes of Urocortins) in heart failure.
In this study, we will examine the effects and mechanisms of Urocortins 2 \& 3 on forearm blood flow and release of natural blood clot dissolving factors in the forearm circulation of healthy volunteers. In particular, we look at the endothelial mechanisms of vasodilatation of Urocortin 2 and 3.
In this study, we will look at the role of the lining of the blood vessel (endothelium) in response to urocortin types 2 and 3. We hypothesise that urocortins 2 \& 3 act via the endothelium to cause dilatation of the blood vessels and release of tissue-plasminogen activating factor (blood clot dissolving factor). We also hypothesise that urocortins have a role in maintaining the normal baseline level of blood flow in forearm arteries. In addition to the above, we will also look at the effect of temporarily blocking the effect of urocortins, using a specially designed blocker drug (Astressin 2B).
Utilising the well-established technique of 'forearm venous occlusion plethysmography', we will be able to focus on the local effects of urocortins on arterial blood flow in forearm vessels, without affecting this system in the body as a whole.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
- Healthy male volunteers between 18 - 65 years (inclusive)
- Lack of informed consent- Age <18 years > 65 years
- Current involvement in a clinical trial
- Severe or significant co-morbidity including bleeding diathesis, renal or hepatic failure
- Smoker
- History of anaemia
- Recent infective/inflammatory condition
- Recent blood donation (prior 3 months)
- Positive baseline urine test for drugs of abuse (including cannabinoids, benzodiazepines, opiates, cocaine and amphetamines)
- History of allergy to Aspirin
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Nitric Oxide Clamp NO clamp Forearm blood flow response to Urocortins 2, 3 and Substance P in the presence of Nitric Oxide clamp Saline Placebo Saline Forearm blood flow response to Urocortin 2, Urocortin 3 and Substance P in the presence of saline placebo. Combined Combined Forearm blood flow response to Urocortin 2, Urocortin 3 and Substance P in the presence of inhibition of cycloxygenase, EDHF and NO pathways with Aspirin, Fluconazole and NO clamp. Fluconazole Fluconazole Forearm blood flow response to Urocortin 2, Urocortin 3 and Substance P in the presence of intra-arterial Fluconazole. Aspirin Aspirin Forearm blood flow response to Urocortin 2, Urocortin 3 and Substance P in the presence of cyclooxygenase inhibition with Aspirin.
- Primary Outcome Measures
Name Time Method Forearm blood flow 3 hours The difference between forearm blood flow in response to incremental doses of Ucn2, Ucn3 and Sub P in the presence vs absence of 'the nitric oxide clamp'
- Secondary Outcome Measures
Name Time Method Net t-PA release 3 hours Net release of t-PA evoked by Ucn 2, Ucn 3 and Substance P, in the presence vs absence of a 'nitric oxide clamp'.
Trial Locations
- Locations (1)
Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh
🇬🇧Edinburgh, Mid Lothian, United Kingdom