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

Heart Failure Clinical Trial

Official title:

Effects of Urocortins on Forearm Arterial Blood Flow in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01296607
• Other study ID #: SV.Protocol 4
• Status: Completed
• Phase: N/A
• First received: February 14, 2011
• Last updated: August 31, 2011
• Start date: February 2011
• Est. completion date: July 2011

Study information

• Verified date: August 2011
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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)

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Heart Failure

Intervention

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
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.

Locations

Country	Name	City	State
United Kingdom	Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh	Edinburgh	Mid Lothian

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	NHS Lothian

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow	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	3.5 hours	Yes
Secondary	Plasma Urocortin 2 and 3 levels	Change in plasma levels of Urocortin 2 and 3 in response to intra-arterial infusion of Urocortin 2 and 3 respectively.	3.5 hours	No