Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

NCT01049542 | Completed

• 1 other identifier: SV.Protocol1
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Vascular Disease; Heart Disease

Keywords

Astressin 2B; Forearm blood flow; vascular; plethysmography; heart failure

Outcome Measures

Primary Outcomes (1)

• Change in forearm blood flow

  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

  3 hours

Secondary Outcomes (1)

• Principle safety assessment, heart rate and blood pressure

  3 hours

Study Arms (1)

Astressin 2B

EXPERIMENTAL

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

Interventions

Astressin 2B DRUG

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.

Also known as: Forearm vascular study

Astressin 2B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Edinburgh: lead

Study Sites (1)

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, Mid Lothian, EH16 4SA, United Kingdom

Location

MeSH Terms

Conditions

Vascular Diseases; Heart Diseases; Heart Failure

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Study Officials

• David E Newby, PhD FRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 14, 2010
• Study Start: May 1, 2010
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: November 16, 2010

Record last verified: 2010-11

Locations

GB (1)