Back to results

Evaluation of the Effects of Urotensin-II and Soluble Epoxide Hydrolase Inhibitors on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers

Primary Purpose

Heart Failure

Status

Completed

Phase

Phase 2

Locations

Australia

Study Type

Interventional

Intervention

Urotensine II

Soluble epoxide hydrolase

About this trial

This is an interventional basic science trial for Heart Failure focused on measuring Urotensin II, Soluble epoxide hydrolase, Iontophoresis, Healthy volunteers

Eligibility Criteria

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

Inclusion Criteria:

Confirmed written informed consent.
Male/Female over 18 and under 80 years of age.
Females must be non-pregnant, non-lactating and using reliable means of contraception (surgical sterilisation or a barrier method such as a condom). The oral contraceptive pill is an exclusion to this study.
Patients with CHF will be required to have left ventricular fractional shortening [LVFS] of <22% or LVEF < 40% and New York Heart Association functional class [NYHA FC] II-III symptoms
Body mass index (BMI) between 18-35 kg/m2.
Screening clinical laboratory tests including liver function tests and HbA1c are within the normal reference range for the investigative site.
Electrocardiogram (ECG) results considered within normal limits, as determined by the Investigator.

Exclusion Criteria:

Smokers
History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neurological, or other disorders capable of altering the absorption, metabolism, or elimination of drugs, or of constituting a risk factor when exposed to the study medication.
Those requiring concomitant medications that will affect cardiovascular or endothelial function or blood pressure control (eg cholesterol lowering medication, hormone replacement therapy, aspirin, NSAIDS).
Patients receiving Hormone Replacement Therapy.
Known allergy or hypersensitivity to urotensin or urotensin receptor antagonists or its excipients, or related drugs, or a history of relevant adverse drug reactions of any origin.
Regular alcohol intake greater than 14 units/week or is unwilling to comply with the alcohol prohibition for the duration of the study (1 unit of alcohol is equivalent to: 12 ounces of beer, 4 ounces of wine, or 1 ounce of 50-proof hard liquor).
History of drug abuse.
Screening biochemistry > 20 % outside normal limits.
Patients who are thought to be terminally ill or immuno-compromised
Patients who have previously been enrolled in this study or have received other experimental medications in the last 4 weeks.
Patients who are unlikely to comply with study procedures

Sites / Locations

Alfred Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm Description

Heart failure patients

Healthy subjects

Outcomes

Primary Outcome Measures

To compare the vasoactive role of Soluble epoxide hydrolase in the healthy subjects and CHF patients with iontophoresis.

Secondary Outcome Measures

Full Information

NCT ID

NCT00654966

First Posted

April 3, 2008

Last Updated

July 19, 2011

Sponsor

Monash University

1. Study Identification

Unique Protocol Identification Number

NCT00654966

Brief Title

Evaluation of the Effects of Urotensin-II and Soluble Epoxide Hydrolase Inhibitors on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers

Official Title

Evaluation of the Effects of Urotensin-II and Soluble Epoxide Hydrolase Inhibitors on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers.

Study Type

Interventional

2. Study Status

Record Verification Date

July 2011

Overall Recruitment Status

Completed

Study Start Date

June 2009 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Monash University

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Urotensin II (U-II) is newly discovered protein that may play an important role in human health and disease. U-II has been found to be a potent vasoconstrictor (narrower of blood vessels) which therefore may be involved in important diseases such as chronic heart failure - CHF (weak heart muscle disease). Many vasoconstrictors have been found to have effects on key organs such as the heart. Preliminary data by our group have demonstrated this is true of U-II. Recent evidence shows that in CHF, U-II levels in the blood are increased. The proposed study seek to determine the effect of blocking a possible downstream mediator of U-II on blood vessels by administration of soluble epoxide hydrolase inhibitor (sEHI). There will be 2 study groups 1) Healthy volunteers and, 2) CHF patients. Each arm of the study will run independently and will require 16 participants each (16 normal subjects and 16 CHF subjects). Participants will be screened to ensure that they are eligible. CHF patients will be required to withdraw from their CHF medication 24 hours prior to the study day (except for diuretics). On the study day, sEHI will be administered on the skin of participants in 3 asceding dosages. The technique to be used is iontophoresis. This is a non invasive technique in which a small amount of the compound is placed on the skin of the forearm. The drug is delivered across the skin by passing a small electric current over the area. The change in blood flow is then measured and analysed. We will also administer U-II agonist, noradrenaline, and distilled water (all via iontophoresis). Noradrenaline will be used a positive constrictor control. Change in blood flow will be assessed by Laser Doppler Velocimetry. If it is found that the sEHI is able to prevent blood vessel constriction in CHF patients, then it may represent a major therapeutic advance in the management of CHF.

6. Conditions and Keywords

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

Heart Failure

Keywords

Urotensin II, Soluble epoxide hydrolase, Iontophoresis, Healthy volunteers

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Heart failure patients

Arm Title

Arm Type

Active Comparator

Arm Description

Healthy subjects

Intervention Type

Drug

Intervention Name(s)

Urotensine II

Intervention Description

A few drops of the drug will be administered to the skin by iontophoresis.

Intervention Type

Drug

Intervention Name(s)

Soluble epoxide hydrolase

Intervention Description

A few drops of the drug will be administered to the skin by iontophoresis.

Primary Outcome Measure Information:

Title

To compare the vasoactive role of Soluble epoxide hydrolase in the healthy subjects and CHF patients with iontophoresis.

Time Frame

2 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: Confirmed written informed consent. Male/Female over 18 and under 80 years of age. Females must be non-pregnant, non-lactating and using reliable means of contraception (surgical sterilisation or a barrier method such as a condom). The oral contraceptive pill is an exclusion to this study. Patients with CHF will be required to have left ventricular fractional shortening [LVFS] of <22% or LVEF < 40% and New York Heart Association functional class [NYHA FC] II-III symptoms Body mass index (BMI) between 18-35 kg/m2. Screening clinical laboratory tests including liver function tests and HbA1c are within the normal reference range for the investigative site. Electrocardiogram (ECG) results considered within normal limits, as determined by the Investigator. Exclusion Criteria: Smokers History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neurological, or other disorders capable of altering the absorption, metabolism, or elimination of drugs, or of constituting a risk factor when exposed to the study medication. Those requiring concomitant medications that will affect cardiovascular or endothelial function or blood pressure control (eg cholesterol lowering medication, hormone replacement therapy, aspirin, NSAIDS). Patients receiving Hormone Replacement Therapy. Known allergy or hypersensitivity to urotensin or urotensin receptor antagonists or its excipients, or related drugs, or a history of relevant adverse drug reactions of any origin. Regular alcohol intake greater than 14 units/week or is unwilling to comply with the alcohol prohibition for the duration of the study (1 unit of alcohol is equivalent to: 12 ounces of beer, 4 ounces of wine, or 1 ounce of 50-proof hard liquor). History of drug abuse. Screening biochemistry > 20 % outside normal limits. Patients who are thought to be terminally ill or immuno-compromised Patients who have previously been enrolled in this study or have received other experimental medications in the last 4 weeks. Patients who are unlikely to comply with study procedures

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Henry Krum, MBBS FRACP PhD

Organizational Affiliation

Monash University / Alfred Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Alfred Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

12. IPD Sharing Statement

Learn more about this trial

Evaluation of the Effects of Urotensin-II and Soluble Epoxide Hydrolase Inhibitors on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers

We'll reach out to this number within 24 hrs