Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers (Protocol 2)

Not Applicable

Completed

• Conditions: Vascular Disease; Heart Disease
• Interventions: Drug: Saline placebo; Drug: Urocortin 2, Urocortin 3

• Registration Number: NCT01096693
• 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-03-30
• Study First Submitted QC: 2010-03-30
• Study First Posted: 2010-03-31
• Study Start: 2010-08
• Primary Completion: 2012-08
• Study Completion: 2014-08-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-05-01
• Last Update Posted: 2024-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 12

Inclusion Criteria

• Healthy male volunteers between 18 - 65 years (inclusive)

Exclusion Criteria

• 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Saline Placebo	Saline placebo	In this arm, the response in forearm blood flow to incremental doses of Urocortins 2, 3 and Substance P will be studied co infused with saline placebo.
Response to Urocortin infusion in presence of Astressin 2B	Urocortin 2, Urocortin 3	This arm studies the response to intra arterial infusion of incremental doses of Urocortins 2, 3 and Substance P in the presence or absence of a selective antagonist - Astressin 2B.

Primary Outcome Measures

Name	Time	Method
Forearm blood flow	2.30 hours	Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P in the presence vs absence of Astressin 2B dose 1 and in the presence vs absence of Astressin 2B dose 2

Secondary Outcome Measures

Name	Time	Method
Net t-PA release	2.30 hours	Net t-PA release induced by Ucn2 and Ucn3 in the presence vs absence of Astressin 2B dose 1 and in the presence vs the absence of Astressin 2B dose 2.

Trial Locations

Locations (1)

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh; 🇬🇧 Edinburgh, Mid Lothian, United Kingdom