Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers
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 and the Corticotrophin Releasing Hormone Receptor Type 2 (CRH-R2) receptor (through which urocortins act) on forearm blood flow and release of natural blood clot dissolving factors in the forearm circulation of healthy volunteers.
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
|Official Title:||Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers|
- Change in forearm blood flow [ Time Frame: 3 hours ] [ Designated as safety issue: No ]Absolute change in forearm blood flow with respect to baseline forearm blood flow resulting from infusion of the study drugs, using forearm venous occlusion plethysmography
- Principle safety assessment, heart rate and blood pressure [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2010|
|Study Completion Date:||July 2010|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: Astressin 2B
Healthy volunteers will receive incremental doses of intra arterial Astressin 2B (a selective and potent Urocortin 2 & 3 antagonist). This serves as a dose finding Protocol for Astressin 2B, which will be used in subsequent protocols.
Drug: Astressin 2B
After an initial saline washout, increasing doses of Astressin 2B (at 0.032, 0.32, 3.2, 32, 320 and 3200 pmol/min) will be infused, for 10 minutes at each dose,intra arterially using forearm venous occlusion plethysmography. Forearm blood flow will be measured with each incremental dose of Astressin 2B.
Other Name: Forearm vascular study
|Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh|
|Edinburgh, Mid Lothian, United Kingdom, EH16 4SA|
|Principal Investigator:||David E Newby, PhD FRCP||University of Edinburgh|