Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

University of Edinburgh

Status: Completed

Conditions: Vascular Disease; Heart Disease

Treatments: Drug: Astressin 2B

Study type: Interventional

Funder types: Other

Identifiers

NCT01049542

SV.Protocol1

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: Male

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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)

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: Single Blind

---

6 participants in 1 patient group

Astressin 2B

Experimental group

Description:

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.

Treatment:

Drug: Astressin 2B