Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000539033
Ethics application status
Approved
Date submitted
17/05/2010
Date registered
6/07/2010
Date last updated
12/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
The immediate effects of the hOrmone Urocortin on the nerve Control of blood pressure and Heart ratE.
Scientific title
The immediate effects of Urocortin 2 on Muscle Sympathetic Nerve Activity and haemodynamics in healthy men versus men with stable heart failure
Secondary ID [1] 251780 0
none
Universal Trial Number (UTN)
Trial acronym
Touché
Linked study record

Health condition
Health condition(s) or problem(s) studied:
blood pressure and stable heart failure 257375 0
Condition category
Condition code
Cardiovascular 257523 257523 0 0
Normal development and function of the cardiovascular system
Cardiovascular 257820 257820 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We propose to determine whether Urocortin 2 (Ucn2) can inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure.
Participants will receive in a random order either Ucn2 (25 ug ) or matching placebo infusions over 60minutes on 2 separate occasions separated by 8 weeks. Each study day will occur on the third day of identical and constant salt controlled diets (Sodium 120mmol/day, Potassium 100mmol/day for 2 days prior to the infusion on Day 3.
On the morning of each study day, subjects will positioned in a lazy-boy reclined chair where they will remain for the duration of the study. Microneurography needles will be inserted in the right superficial peroneal nerve in the lower leg. Blood pressure and nerve activity recordings will be measured continuously and blood sampling will occur at 15 minute intervals from 30 minutes prior to infusion to 2 hours after.
Intervention code [1] 256482 0
Diagnosis / Prognosis
Comparator / control treatment
59.6mls normal saline
Control group
Placebo

Outcomes
Primary outcome [1] 258439 0
That Urocortin 2 will lower Mean Arterial Pressure (MAP) and calculated total peripheral resistance (CTPR) and increase Hear Rate (HR) and cardiac output. Continuous arterial pressure and heart rate will be obtained using the FINAPRES system, a photoplethysmographic device based on the volume-clamp technique. Stroke volume and therefore caridac output and CTPR can be derived from the arterial pulsewave for each heartbeat using the MODELFLOW method.
Timepoint [1] 258439 0
Haemodynamic recordings will be collected continuously and analysed at 15 minute intervals from 30 minutes prior to the infusion to 2 hours afterwards.
Primary outcome [2] 258721 0
Urocortin 2 will result in either no change or a decrease in Muscle Sympathetic Nerve Activity (MSNA). MSNA will be recorded by microneurography needles inserted in the right superficial peroneal nerve for postganlionic MSNA. The burst frequency and burst area will be analysed in 5min block.
Timepoint [2] 258721 0
Nerve activity will be recorded continuously and blood sampling will occur at 15 minute intervals from 30 minutes prior to infusion to 2 hours aftrewards. Nerve activity will be analysed in 5 minute blocks.
Secondary outcome [1] 264222 0
nil
Timepoint [1] 264222 0
nil

Eligibility
Key inclusion criteria
Part 1 Inclusion:
Absence of significant respiratory, liver or renal disease, or active malignancy.
No drugs affecting haemodynamics or sympathetic nerve activity
Part 2: Inclusion
Stable left ventricular dysfunction with left ventricular ejection fraction <40%
New York Heart Association (NYHA) class II or III symptoms
Absence of significant respiratory, liver or renal disease, or active malignancy.
Minimum age
18 Years
Maximum age
60 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion: peripheral neuropathy, atrial fibrillation, autonomic failure, chronic hypotension
Inability to give informed consent

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The sample size of 8 healthy and 8 stable heart failure participants in a crossover design is based on pragmatic rather than formal statistical criteria. This is a standard sample size for phase I/IIa studies of this type, seeking to affirm safety results from earlier studies and provide signals of potential efficacy.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
A cross-over design of UCN2 and placebo infusion in a random order. A randomisation scheme will be established in advance for both parts of this study. This randomisation will determine the sequence in which the two treatments are delivered to the participants. This randomisation scheme will be constructed in the manner of a balanced latin-Square design with the sequence allocation remaining blinded to the investigators.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2010
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment outside Australia
Country [1] 2630 0
New Zealand
State/province [1] 2630 0

Funding & Sponsors
Funding source category [1] 256974 0
Government body
Name [1] 256974 0
Health Research Council of New Zealand
Country [1] 256974 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of New Zealand
Address
PO Box 5541
Wellesley Street,
Auckland1141
New Zealand
Country
New Zealand
Secondary sponsor category [1] 256234 0
None
Name [1] 256234 0
Address [1] 256234 0
Country [1] 256234 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258988 0
Upper South B regional Ethics Committee
Ethics committee address [1] 258988 0
Ministry of Health
PO Box 3877
Christchurch 8140
Ethics committee country [1] 258988 0
New Zealand
Date submitted for ethics approval [1] 258988 0
Approval date [1] 258988 0
31/03/2010
Ethics approval number [1] 258988 0

Summary
Brief summary
Cardiovascular disease is a leading cause of death and significant burden on our health system. Existing drug treatments remain less than ideal. We need additional effective strategies for management of these patients. Reducing sympathetic nerve firing directed at the heart, which may exacerbate heart damage and cause sudden death, is desirable following heart attacks. A family of hormones, the urocortins (Ucn), have been proposed as novel therapeutic agents in this setting. We propose to determine whether Ucn can also inhibit sympathetic nerve activity (measured in the leg) in 8 healthy male volunteers and 8 males with stable heart failure.
Participants will receive in a random order either Ucn2 (25 ug over 60 min) or matching placebo infusions on 2 separate occasions separated by 8 weeks. Each study day will occur on the fourth day of identical and constant salt controlled diets. On the morning of each study day, subjects will positioned in a lazy-boy reclined chair where they will remain for the duration of the study. Microneurography needles will be inserted in the right superficial peroneal nerve in the lower leg. Blood pressure will be measured continuously throughtout the infusion. Nerve activity recordings and blood sampling will occur at 5-15 minute intervals from 30 minutes prior to infusion for 2 hours
These studies should clarify the true therapeutic potential of Ucn in cardiovascular disease.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31168 0
Address 31168 0
Country 31168 0
Phone 31168 0
Fax 31168 0
Email 31168 0
Contact person for public queries
Name 14415 0
Associate Professor David Jardine
Address 14415 0
Canterbury District Health Board
General Medicine
Christchurch Hospital
Private Bag 4710
Christchurch 8140
Country 14415 0
New Zealand
Phone 14415 0
+643 364 0640
Fax 14415 0
Email 14415 0
[email protected]
Contact person for scientific queries
Name 5343 0
Associate Professor David Jardine
Address 5343 0
Canterbury District Health Board
General Medicine
Christchurch Hospital
Private Bag 4710
Christchurch 8140
Country 5343 0
New Zealand
Phone 5343 0
+643 364 0640
Fax 5343 0
Email 5343 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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