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

Heart Disease Clinical Trial

Official title:

Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01096693
• Other study ID #: SV.Procotol 2
• Status: Completed
• Phase: N/A
• Start date: August 2010
• Est. completion date: August 31, 2014

Study information

• Verified date: April 2024
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 31, 2014
• Est. primary completion date: August 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Heart Disease
• Heart Diseases
• Vascular Disease
• Vascular Diseases

Intervention

Drug:
• Urocortin 2, Urocortin 3
After a 20 minute infusion of intra arterial saline, healthy volunteers will receive ascending doses of intra arterial Urocortin 2 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively), Urocortin 3 (3.4, 34 and 340 pmol/min to achieve estimated end-organ concentrations of 0.06, 0.6 and 6 µg/L, respectively) and Substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]). This will be co-infused with either Astressin 2B (in one of the two doses determined from Protocol 1) or saline placebo. Bilateral venous blood sampling will be performed at baseline, immediately before the start and after each dose of Urocortin 2 and 3, to later estimate net release of tPA and PAI-1 and for plasma measurements of Urocortins 2 and 3.
• Saline placebo
After 20 minutes of intra arterial saline infusion, incremental doses of Urocortin 2, 3 and Substance P will be administered (in doses similar to Active comparator arm), co infused with saline placebo. Bilateral venous blood samples will be taken at baseline, immediately before the start of Ucn2/Ucn3 infusion and at the end of each dose of Ucn2/Ucn3 for subsequent calculation of net release of t-PA and PAI-1.

Locations

Country	Name	City	State
United Kingdom	Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh	Edinburgh	Mid Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow	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	2.30 hours
Secondary	Net t-PA release	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.	2.30 hours