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

February 14, 2011
August 31, 2011
February 2011
June 2011   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01296607 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers - Protocol 4
Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

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.

Not Provided
Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
  • Cardiovascular Disease
  • Heart Failure
  • 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.

  • 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.

  • 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.
    Intervention: Drug: Urocortin 2
  • 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.
    Intervention: Drug: Urocortin 3
Venkatasubramanian S, Griffiths ME, McLean SG, Miller MR, Luo R, Lang NN, Newby DE. Vascular effects of urocortins 2 and 3 in healthy volunteers. J Am Heart Assoc. 2013 Jan 31;2(1):e004267. doi: 10.1161/JAHA.112.004267.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
12
July 2011
June 2011   (final data collection date for primary outcome measure)

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)
Male
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United Kingdom
 
NCT01296607
SV.Protocol 4
No
University of Edinburgh
University of Edinburgh
NHS Lothian
Principal Investigator: David E Newby, PhD, FRCP University of Edinburgh
University of Edinburgh
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP