Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01049542
First received: January 12, 2010
Last updated: November 15, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention
Vascular Disease
Heart Disease
Drug: Astressin 2B

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Principle safety assessment, heart rate and blood pressure [ Time Frame: 3 hours ] [ Designated as safety issue: Yes ]

Enrollment: 6
Study Start Date: May 2010
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049542

Locations
United Kingdom
Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh
Edinburgh, Mid Lothian, United Kingdom, EH16 4SA
Sponsors and Collaborators
University of Edinburgh
Investigators
Principal Investigator: David E Newby, PhD FRCP University of Edinburgh
  More Information

No publications provided

Responsible Party: Prof D E Newby, University of Edinburgh
ClinicalTrials.gov Identifier: NCT01049542     History of Changes
Other Study ID Numbers: SV.Protocol1
Study First Received: January 12, 2010
Last Updated: November 15, 2010
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Astressin 2B
Forearm blood flow
vascular
plethysmography
heart failure

Additional relevant MeSH terms:
Heart Diseases
Vascular Diseases
Cardiovascular Diseases
Astressin
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014