Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers - Protocol 4
Condition: Cardiovascular Disease; Heart Failure
MeSH terms: Heart Failure; Cardiovascular Diseases
Study type: Interventional

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 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.
    


Intervention name(s): Urocortin 2; Urocortin 3
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Pharmacodynamics; Pharmacokinetics; Urocortin 2; Urocortin 3; Reproducibility; Onset/ Offset; Forearm blood flow; Plethysmography; Heart Failure