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Effect of Urocortins in Patients With Heart Failure

Primary Purpose

Heart Failure, Endothelium

Status

Completed

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Urocortin 2, Urocortin 3 and Substance P

About this trial

This is an interventional basic science trial for Heart Failure focused on measuring Urocortin 2, Urocortin 3, Forearm venous occlusion plethysmography, Heart failure, Endothelium, Substance P

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Patients with heart failure

Healthy controls

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Absolute forearm blood flow

Absolute forearm arterial blood flow in response to Ucn2, Ucn3 and Substance P.

Full Information

NCT ID

NCT01599728

First Posted

May 14, 2012

Last Updated

June 24, 2013

Sponsor

University of Edinburgh

Collaborators

NHS Lothian

1. Study Identification

Unique Protocol Identification Number

NCT01599728

Brief Title

Effect of Urocortins in Patients With Heart Failure

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Completed

Study Start Date

May 2012 (undefined)

Primary Completion Date

July 2012 (Actual)

Study Completion Date

July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Edinburgh

Collaborators

NHS Lothian

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Heart Failure, Endothelium

Keywords

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

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Non-Randomized

Enrollment

22 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Patients with heart failure

Arm Type

Other

Arm Description

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

Arm Title

Healthy controls

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Urocortin 2, Urocortin 3 and Substance P

Intervention Description

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.

Primary Outcome Measure Information:

Title

Forearm blood flow

Description

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

Time Frame

3 hours

Secondary Outcome Measure Information:

Title

Absolute forearm blood flow

Description

Absolute forearm arterial blood flow in response to Ucn2, Ucn3 and Substance P.

Time Frame

3 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David E Newby, PhD, FRCP

Organizational Affiliation

University of Edinburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wellcome Trust Clinical Research Facility, Royal Infirmary of Edinburgh

City

Edinburgh

ZIP/Postal Code

EH16 4SA

Country

United Kingdom

12. IPD Sharing Statement

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Effect of Urocortins in Patients With Heart Failure

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