Evaluation of the Effects of Urotensin-II and Urotensin-II Antagonist on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers - Full Text View

Sponsored by:	Monash University
Information provided by:	Monash University
ClinicalTrials.gov Identifier:	NCT00654966

Purpose

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 U-II action on blood vessels by administration of a U-II antagonist (blocker). 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, U-II antagonist will be administered on the skin of participants in various settings. 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 analyzed. We will also administer U-II itself, noradrenaline, and distilled water. Noradrenaline will be used a positive constrictor control. If it is found that U-II blocker is able to prevent blood vessel constriction in CHF patients, then it may represent a major therapeutic advance in the management of CHF.

Condition	Intervention	Phase
Heart Failure	Drug: Urotensine II Drug: ENC8003 (Urotensin II antagonist)	Phase II

Study Type:	Interventional
Study Design:	Basic Science, Open Label, Active Control, Parallel Assignment
Official Title:	Evaluation of the Effects of Urotensin-II and Urotensin-II Antagonist on Skin Microvessel Tone in Patients With Heart Failure, and in Healthy Volunteers.

Resource links provided by NLM:

MedlinePlus related topics: Heart Failure

Drug Information available for: Urotensin II

U.S. FDA Resources

Further study details as provided by Monash University:

Primary Outcome Measures:

To compare the vasoactive role of U-II antagonism in the healthy subjects and CHF patients with iontophoresis. [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Enrollment:	0
Study Start Date:	June 2008
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Heart failure patients	Drug: Urotensine II A few drops of the drug will be administered to the skin by iontophoresis. Drug: ENC8003 (Urotensin II antagonist) A few drops of the drug will be administered to the skin by iontophoresis.
2: Active Comparator Healthy subjects	Drug: Urotensine II A few drops of the drug will be administered to the skin by iontophoresis. Drug: ENC8003 (Urotensin II antagonist) A few drops of the drug will be administered to the skin by iontophoresis.

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00654966

Locations

Australia, Victoria
Alfred Hospital
Melbourne, Victoria, Australia, 3004

Sponsors and Collaborators

Monash University

Investigators

Principal Investigator:

Henry Krum, MBBS FRACP PhD

Monash University / Alfred Hospital

More Information

No publications provided

Responsible Party:	Monash University / Alfred Hospital ( Prof Henry Krum )
Study ID Numbers:	CP-02/08, 77/08
Study First Received:	April 3, 2008
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00654966 History of Changes
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Monash University:

Urotensin II
Urotensin II antagonist
Iontophoresis
Healthy volunteers

Study placed in the following topic categories:

Heart Failure
Heart Diseases
Healthy

Additional relevant MeSH terms:

Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 09, 2009