Effect of Urocortins in Patients With Heart Failure

NCT ID: NCT01599728

Last Updated: 2013-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2012-07-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Patients with heart failure

Assessing the response to infusion of intra-arterial Urocortin 2, 3 and Substance P in patients with heart failure

Group Type: OTHER

Urocortin 2, Urocortin 3 and Substance P

Intervention Type: 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

Assessing response to intra-arterial infusions of Urocortin 2, 3 and Substance P in age and sex-matched healthy volunteers as controls.

Group Type: OTHER

Urocortin 2, Urocortin 3 and Substance P

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David E Newby, PhD, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Edinburgh

Locations

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Countries

United Kingdom

Other Identifiers

UcnHFP2

Identifier Type: -

Identifier Source: org_study_id