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Effect of Urocortins in Patients With Heart Failure

This study is not yet open for participant recruitment.
Verified May 2012 by University of Edinburgh
Sponsor:
Collaborator:
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01599728
First received: May 14, 2012
Last updated: May 15, 2012
Last verified: May 2012
History of Changes
  Purpose

Despite modern advances in treatment, heart failure continues to carry a poor prognosis with high morbidity and mortality rates. Hence, there remains a major interest in the development of novel therapeutic agents for this debilitating condition. Urocortins have recently shot into limelight with their potential role in the pathophysiology and treatment of heart failure.

Recent studies by the investigators group (REC no: 09/S1103/41) have confirmed that Urocortin 2 and 3 are potent arterial vasodilators, the effects of which are reproducible and well tolerated in healthy male volunteers. Previous studies using heart failure models in animals1-7, as well studies in heart failure patients (Urocortin 2), suggest that there is great scope for Urocortins as novel biomarkers and as potential therapeutic agents in heart failure. With this in mind, the investigators wish to study the local vasomotor effects of these peptides in greater detail in patients with heart failure.


Condition Intervention
Heart Failure
Endothelium
 Drug: Urocortin 2, Urocortin 3 and Substance P

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Urocortins 2 & 3-Effects on Forearm Arterial Blood Flow in Patients With Heart Failure

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure
U.S. FDA Resources

Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Forearm blood flow [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P between heart failure patients and healthy controls.


Secondary Outcome Measures:
  • Absolute forearm blood flow [ Time Frame: 3 hours ] [ Designated as safety issue: No ]
    Absolute forearm arterial blood flow in response to Ucn2, Ucn3 and Substance P.


Estimated Enrollment: 24
Study Start Date: May 2012
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Patients with heart failure
Assessing the response to infusion of intra-arterial Urocortin 2, 3 and Substance P in patients with heart failure
 Drug: Urocortin 2, Urocortin 3 and Substance P

After a 20-min infusion of intra-arterial saline, ascending doses of Urocortin 2 (3.6, 12 and 36 pmol/min [15, 50 and 150 ng/min] to achieve estimated end-organ concentrations of 0.6, 2 and 6 µg/L, respectively), Urocortin 3 1200, 3600 and 12000 pmol/min (5, 15 and 50 micrograms/min) [to achieve estimated end-organ concentrations of 199, 600 and 2000 micrograms/L respectively] and substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]) will be administered intra-arterially.

Baseline blood samples will be taken at the start of the study for full blood count, cholesterol, glucose, renal function Bilateral venous blood samples will be taken at baseline, immediately before the start of Ucn2/Ucn3 infusion and at the end of each dose of Ucn2/Ucn3 for subsequent measurement of plasma Ucn 2 and 3 concentrations and other hormones.
Healthy controls
Assessing response to intra-arterial infusions of Urocortin 2, 3 and Substance P in age and sex-matched healthy volunteers as controls.
 Drug: Urocortin 2, Urocortin 3 and Substance P

After a 20-min infusion of intra-arterial saline, ascending doses of Urocortin 2 (3.6, 12 and 36 pmol/min [15, 50 and 150 ng/min] to achieve estimated end-organ concentrations of 0.6, 2 and 6 µg/L, respectively), Urocortin 3 1200, 3600 and 12000 pmol/min (5, 15 and 50 micrograms/min) [to achieve estimated end-organ concentrations of 199, 600 and 2000 micrograms/L respectively] and substance P (a control endothelium-dependent vasodilator that evokes endogenous t-PA release [2, 4 and 8 pmol/min]) will be administered intra-arterially.

Baseline blood samples will be taken at the start of the study for full blood count, cholesterol, glucose, renal function Bilateral venous blood samples will be taken at baseline, immediately before the start of Ucn2/Ucn3 infusion and at the end of each dose of Ucn2/Ucn3 for subsequent measurement of plasma Ucn 2 and 3 concentrations and other hormones.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patients with heart failure:

  1. Patients with stable heart failure (NYHA class II-IV) on maximum tolerated doses of an ACE inhibitor and beta-blocker for at least 3 months.
  2. Baseline echocardiographic parameters (echo performed within last 12 months) at recruitment: ejection fraction (EF) <35%, left ventricular end dimension >5.5cm and fractional shortening <20%
  3. Age 18-80 years (inclusive) at recruitment

Healthy volunteers:

  • Age and sex-matched healthy volunteers

Exclusion Criteria:

  1. Lack of informed consent
  2. Age <18 years and > 80 years
  3. Current involvement in a clinical trial
  4. Systolic blood pressure >190 mmHg or <90 mmHg, untreated malignant arrhythmias
  5. Haemodynamically significant valvular heart disease
  6. Severe or significant co-morbidity including bleeding diathesis, renal or hepatic failure
  7. History of anaemia
  8. Recent infective/inflammatory condition
  9. Recent blood donation (prior 3 months)
  10. Women of child bearing potential
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01599728

Contacts
Contact: Sowmya Venkatasubramanian, MBBS, MRCP 0044 131 242 6364 s.venkat@ed.ac.uk
Contact: Ninian N Lang, PhD, MRCP ninian.lang@me.com

Locations
United Kingdom
Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh Not yet recruiting
Edinburgh, United Kingdom, EH16 4SA
Sub-Investigator: Sowmya Venkatasubramanian, MBBS, MRCP            
Sub-Investigator: Ninian N Lang, PhD, MRCP            
Principal Investigator: David E Newby, PhD, FRCP            
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Investigators
Principal Investigator: David E Newby, PhD, FRCP University of Edinburgh
  More Information

No publications provided

Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01599728     History of Changes
Other Study ID Numbers: UcnHFP2
Study First Received: May 14, 2012
Last Updated: May 15, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by University of Edinburgh:
Urocortin 2
Urocortin 3
Forearm venous occlusion plethysmography
 Heart failure
Endothelium
Substance P

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Substance P
 Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2013