Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers - Protocol 4

This study has been completed.
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01296607
First received: February 14, 2011
Last updated: August 31, 2011
Last verified: August 2011
  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 pharmacokinetics and pharmacodynamics (in particular the onset-offset of action and reproducibility of vasodilator effects) of Urocortins 2 & 3 on forearm arterial blood flow healthy volunteers.

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
Cardiovascular Disease
Heart Failure
Drug: Urocortin 2
Drug: Urocortin 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
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:
  • Forearm blood flow [ Time Frame: 3.5 hours ] [ Designated as safety issue: Yes ]
    Difference in forearm blood flow in response to increasing doses of Urocortin 2 and Urocortin 3 in the presence and absence of saline washout between doses


Secondary Outcome Measures:
  • Plasma Urocortin 2 and 3 levels [ Time Frame: 3.5 hours ] [ Designated as safety issue: No ]
    Change in plasma levels of Urocortin 2 and 3 in response to intra-arterial infusion of Urocortin 2 and 3 respectively.


Estimated Enrollment: 12
Study Start Date: February 2011
Study Completion Date: July 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Urocortin 2
This arm studies the onset/ offset of action and the reproducibility of effect on forearm blood flow of of intra-arterial Urocortin 2 in the presence and absence of a saline washout between incremental doses.
Drug: Urocortin 2

Protocol 4a: Onset/Offset protocol: (Visits 1 or 3)

Following a 20-minute period of saline infusion for equilibration of the set-up, subjects will receive incremental doses of Urocortin 2 in the presence of a saline washout between each dose.

Urocortin 2 will be infused at 3.6, 12, 36 and 120 pmol/min (15, 50, 150 and 498 nanograms/min) to achieve estimated end-organ concentrations of 0.6, 2, 6 and 20 micrograms/L respectively.

Protocol 4b: Reproducibility protocol (Visit 2 or 4)

Following a 20-minute period of saline infusion for equilibration of the set-up, subjects will receive ascending doses of urocortin 2 in the absence of saline washout between each dose. This protocol aims to assess the reproducibility of the vasodilatory effect of urocortin 2 on repeated dosing. The doses used for this protocol will be identical to Protocol a.

Urocortin 3
This arm studies the onset/ offset of action and the reproducibility of effect on forearm blood flow of of intra-arterial Urocortin 3 in the presence and absence of a saline washout between incremental doses.
Drug: Urocortin 3

Protocol 4a: Onset/ Offset protocol: (Visit 1 or 3)

Following a 20-minute period of saline infusion for equilibration of the set-up, subjects will receive incremental doses of Urocortin 2 or Urocortin 3 in the presence of a saline washout between each dose.

Urocortin 3 will be infused at 1200, 3600, 12000 and 36000 pmol/min (5, 15, 50 and 150 micrograms/min) to achieve estimated end organ concentrations of 199, 600, 2000 and 6000 micrograms/L respectively.

Protocol 4b: Reproducibility protocol (Visit 2 or 4)

Following a 20-minute period of saline infusion for equilibration of the set-up, subjects will receive ascending doses of urocortin 3 in the absence of saline washout between each dose. This protocol aims to assess the reproducibility of the vasodilatory effect of 3 on repeated dosing. The doses used for this protocol will be identical to Protocol a.


  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: NCT01296607

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
NHS Lothian
Investigators
Principal Investigator: David E Newby, PhD, FRCP University of Edinburgh
  More Information

No publications provided by University of Edinburgh

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01296607     History of Changes
Other Study ID Numbers: SV.Protocol 4
Study First Received: February 14, 2011
Last Updated: August 31, 2011
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Pharmacodynamics
Pharmacokinetics
Urocortin 2
Urocortin 3
Reproducibility
Onset/ Offset
Forearm blood flow
Plethysmography
Heart Failure

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Failure
Heart Diseases

ClinicalTrials.gov processed this record on August 20, 2014