Effect of Urocortins in Patients With Heart Failure

Heart Failure Clinical Trial

Official title:

Urocortins 2 & 3-Effects on Forearm Arterial Blood Flow in Patients With Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01599728
• Other study ID #: UcnHFP2
• Status: Completed
• Phase: N/A
• First received: May 14, 2012
• Last updated: June 24, 2013
• Start date: May 2012
• Est. completion date: July 2012

Study information

• Verified date: June 2013
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Endothelium
• Heart Failure

Intervention

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.

Locations

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

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 between forearm blood flow in response to doses of Ucn2, Ucn3 and Substance P between heart failure patients and healthy controls.	3 hours	No
Secondary	Absolute forearm blood flow	Absolute forearm arterial blood flow in response to Ucn2, Ucn3 and Substance P.	3 hours	No