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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

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ClinicalTrials.gov Identifier: NCT00654966
Recruitment Status : Completed
First Posted : April 9, 2008
Last Update Posted : July 20, 2011
Sponsor:
Information provided by:
Monash University

April 3, 2008
April 9, 2008
July 20, 2011
June 2009
December 2010   (Final data collection date for primary outcome measure)
To compare the vasoactive role of Soluble epoxide hydrolase in the healthy subjects and CHF patients with iontophoresis. [ Time Frame: 2 hours ]
To compare the vasoactive role of U-II antagonism in the healthy subjects and CHF patients with iontophoresis. [ Time Frame: 2 hours ]
Complete list of historical versions of study NCT00654966 on ClinicalTrials.gov Archive Site
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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
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.

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Heart Failure
  • Drug: Urotensine II
    A few drops of the drug will be administered to the skin by iontophoresis.
  • Drug: Soluble epoxide hydrolase
    A few drops of the drug will be administered to the skin by iontophoresis.
  • Experimental: 1
    Heart failure patients
    Interventions:
    • Drug: Urotensine II
    • Drug: Soluble epoxide hydrolase
  • Active Comparator: 2
    Healthy subjects
    Interventions:
    • Drug: Urotensine II
    • Drug: Soluble epoxide hydrolase
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
32
December 2010
December 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Older Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
Australia
 
 
NCT00654966
CP-02/08
77/08
No
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Prof Henry Krum, Monash University / Alfred Hospital
Monash University
Not Provided
Principal Investigator: Henry Krum, MBBS FRACP PhD Monash University / Alfred Hospital
Monash University
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP