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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00654966




Registration number
NCT00654966
Ethics application status
Date submitted
3/04/2008
Date registered
9/04/2008
Date last updated
20/07/2011

Titles & IDs
Public 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
Scientific 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.
Secondary ID [1] 0 0
77/08
Secondary ID [2] 0 0
CP-02/08
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Urotensine II
Treatment: Drugs - Soluble epoxide hydrolase

Experimental: 1 - Heart failure patients

Active Comparator: 2 - Healthy subjects


Treatment: Drugs: Urotensine II
A few drops of the drug will be administered to the skin by iontophoresis.

Treatment: Drugs: Soluble epoxide hydrolase
A few drops of the drug will be administered to the skin by iontophoresis.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To compare the vasoactive role of Soluble epoxide hydrolase in the healthy subjects and CHF patients with iontophoresis.
Timepoint [1] 0 0
2 hours

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Monash University
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00654966
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Henry Krum, MBBS FRACP PhD
Address 0 0
Monash University / Alfred Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications