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

NCT01296607 | Completed

• 1 other identifier: SV.Protocol 4
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cardiovascular Disease; Heart Failure

Keywords

Pharmacodynamics; Pharmacokinetics; Urocortin 2; Urocortin 3; Reproducibility; Onset/ Offset; Forearm blood flow; Plethysmography; Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Plasma Urocortin 2 and 3 levels

  3.5 hours

Study Arms (2)

Urocortin 2

OTHER

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

Urocortin 3

OTHER

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

Interventions

Urocortin 2 DRUG

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 2

Urocortin 3 DRUG

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 3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy male volunteers between 18 - 65 years (inclusive)

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, Mid Lothian, EH16 4SA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23525432 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Heart Failure

Interventions

Urocortins

Condition Hierarchy (Ancestors)

Heart Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• David E Newby, PhD, FRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2011
• First Posted: February 15, 2011
• Study Start: February 1, 2011
• Primary Completion: June 1, 2011
• Study Completion: July 1, 2011
• Last Updated: September 2, 2011

Record last verified: 2011-08

Locations

GB (1)