Effect of Urocortins in Patients With Heart Failure

NCT01599728 | Completed

• 1 other identifier: UcnHFP2
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Heart Failure; Endothelium

Keywords

Urocortin 2; Urocortin 3; Forearm venous occlusion plethysmography; Heart failure; Endothelium; Substance P

Outcome Measures

Primary Outcomes (1)

• Forearm blood flow

  Difference between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P between heart failure patients and healthy controls.

  3 hours

Secondary Outcomes (1)

• Absolute forearm blood flow

  3 hours

Study Arms (2)

Patients with heart failure

OTHER

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

Healthy controls

OTHER

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

Interventions

Urocortin 2, Urocortin 3 and Substance P DRUG

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; Patients with heart failure

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with heart failure:
• 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.
• 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%
• Age 18-80 years (inclusive) at recruitment
• Healthy volunteers:
• Age and sex-matched healthy volunteers

You may not qualify if:

• Lack of informed consent
• Age \<18 years and \> 80 years
• Current involvement in a clinical trial
• Systolic blood pressure \>190 mmHg or \<90 mmHg, untreated malignant arrhythmias
• Haemodynamically significant valvular heart disease
• Severe or significant co-morbidity including bleeding diathesis, renal or hepatic failure
• History of anaemia
• Recent infective/inflammatory condition
• Recent blood donation (prior 3 months)
• Women of child bearing potential

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Interventions

Urocortins; Substance P

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Tachykinins; Kinins; Intercellular Signaling Peptides and Proteins; Oligopeptides; Proteins; Nerve Tissue Proteins; Autacoids; Inflammation Mediators; Biological Factors

Study Officials

• David E Newby, PhD, FRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2012
• First Posted: May 16, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 25, 2013

Record last verified: 2013-06

Locations

GB (1)