Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000928617
Ethics application status
Approved
Date submitted
23/08/2014
Date registered
29/08/2014
Date last updated
29/08/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Role of Imdur in Cortisol-Induced Hypertension in Humans
Scientific title
The effect oral isosorbide mononitrate on blood pressure in healthy human subjects treated with oral hydrocortisone.
Secondary ID [1] 285209 0
None
Universal Trial Number (UTN)
U1111-1160-7918
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hypertension 292825 0
Condition category
Condition code
Cardiovascular 293126 293126 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Healthy human subjects will be treated with oral hydrocortisone 200mg per day for 5 days. Blood pressure and metabolic parameters will be measured regularly. On the last day of hydrocortisone treatment, a single dose of oral isosorbide mononitrate will be given and the effect of this dose on blood pressure will be measured.Hydrocortisone will be administered at a dose of 50mg four times per day to provide a total daily dose of 200mg hydrocortisone per day. Isosorbide mononitrate will be administered as a single oral dose of 60mg. It will be administered on the morning to the 5th hydrocortisone treatment day prior to the 17th dose of oral hydrocortisone (out of a total of 20 doses of hydrocortisone administered over the whole treatment phase).
Oral hydrocortisone administration at a dose of 200mg per day is expected to result in a number of metabolic changes including weight gain, elevation of white cell count, plasma glucose and cortisol concentrations, and reductions in plasma potassium and haematocrit. Compliance with therapy will be assessed by a pill count on each attendance at the clinical study centre, Additionally at the beginning and end of each treatment phase measurement of body weight, plasma electrolytes, glucose and cortisol concentrations and measurement of haematocrit and white cell count will be undertaken,
There will be a minimum two week wash out period between each treatment phase.
Intervention code [1] 290083 0
Treatment: Drugs
Comparator / control treatment
The study is a double blind placebo control cross-over design. The comparator is a single dose of placebo given on the last day of oral hydrocortisone treatment. In the ‘control phase’ of the study subjects will receive hydrocortisone at a dose of 50mg four times per day to provide a total daily dose of 200mg hydrocortisone per day. Placebo will be administered as a single oral dose. It will be administered on the morning to the 5th hydrocortisone treatment day prior to the 17th dose of oral hydrocortisone (out of a total of 20 doses of hydrocortisone administered over the whole treatment phase). The placebo will be a methyl-cellulose tablet.
Control group
Placebo

Outcomes
Primary outcome [1] 292987 0
The primary outcome is the change in blood pressure on the last day of hydrocortisone treatment after isosorbide mononitrate (or placebo) is co-administered. Blood pressure is measured by standard cuff measurement, and ambulatory blood pressure monitoring.
Timepoint [1] 292987 0
The primary timepoint is the fifth day of hydrocortisone treatment with ambulatory monitoring extending for a further 24 hours after the oral isosorbide mononitrate or placebo is co-administered on day five of oral hydrocortisone treatment,
Primary outcome [2] 292988 0
Central pressure measurements will be assessed non-invasively by applanation tonometery of the radial artery.
Timepoint [2] 292988 0
Day five or oral hydrocortisone treatment after co-administration of isosorbide mononitrate or placebo
Secondary outcome [1] 310091 0
Plasma nitrate / nitrite activity
Timepoint [1] 310091 0
Measured on blood samples taken prior to the administration of oral hydrocortisone and the last day of treatment and two days after treatment is completed

Eligibility
Key inclusion criteria
Healthy male volunteers on no regular medications
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Prior history of high blood pressure or diabetes.
History of allergy to oral compounds in the study protocol.
Any comorbid medical conditions that may be exacerbated by oral hydrocortisone e,g gastro-oesophageal reflux, anxienty, sleep disorder, mood disorder.
Requirment for any regular medication.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All subjects undergo a standardised screening medical questionnaire and physical examination. If there are no contraindications detected to enrolment, the study protocol is explained to the subjects and written informed consent is obtained. A study number which corresponds to the study code held in the dispensing hospital pharmacy is allocated.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The key aspect of randomisation is the co-administration of isosorbide mononitrate or placebo on the last day of oral hydrocortisone therapy. The allocation to co-administration of these compounds is done by the hospital pharmacy using a random number assignment from a random number table. In the second phase of the study the subjects are crossed to the alternate intervention.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
The study is a two phase double-blind placebo controlled cross-over study. Each treatment phase lasts for a total of eight days including a day of pre-treatment observation 5 days of oral hydrocortisone, 24 hours on BP monitoring after co-administration of isosorbide or placebo and two post-treatment assessment days. Each treatment phase is separated by a minimum of a two week wash-out period.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Data analysed using the Systat statistical programme (SYSTAT Version 10, SPSS Inc, 2000) as previously reported. Distribution of data was assessed using the Lilliefors test, and reported as the mean +/- SEM or median, interquartile range. Changes in parameters where more than two measurements were taken tested by repeated-measures analysis of variance (ANOVA). If ANOVA positive, further comparison between groups conducted with t-tests or Wilcoxon techniques as dictated by the distribution of data. Paired data were compared using a paired Student’s t-test if parametric or Wilcoxon sign rank test if non-parametric. Results were corrected for the effects of multiple comparisons using the Hochberg technique.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2007
Actual
13/06/2007
Date of last participant enrolment
Anticipated
30/06/2009
Actual
30/06/2008
Date of last data collection
Anticipated
Actual
Sample size
Target
8
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 289824 0
University
Name [1] 289824 0
John Curtin School of Medical Research, Australian National University, with funding for infrastructure and salary support primary derived from JCSMR.
Country [1] 289824 0
Australia
Funding source category [2] 289861 0
University
Name [2] 289861 0
Department of Medicine, St George Hospital Clinical School, University of New South Wales.
Country [2] 289861 0
Australia
Primary sponsor type
Individual
Name
Dr John Kelly
Address
Department of Renal Medicine
St George Hospital Clinical School
University of New South Wales
50 Montgomery Street
Kogarah. Sydney. NSW. 2217
Country
Australia
Secondary sponsor category [1] 288516 0
None
Name [1] 288516 0
Address [1] 288516 0
Country [1] 288516 0
Other collaborator category [1] 278130 0
Individual
Name [1] 278130 0
Professor Judith Whitworth
Address [1] 278130 0
The John Curtin School of Medical Research
The Australian National University
GPO Box 334
Canberra City ACT 2600
Country [1] 278130 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291557 0
University of New South Wales Human Ethics Commitee
Ethics committee address [1] 291557 0
University of New South Wales Human Research Ethics Committee
UNSW
High Street
Kensington
NSW 2052
Ethics committee country [1] 291557 0
Australia
Date submitted for ethics approval [1] 291557 0
Approval date [1] 291557 0
20/03/2007
Ethics approval number [1] 291557 0
070503

Summary
Brief summary
The purpose of the study is to investigate possible mechanisms by which glucocorticoids raise blood pressure. The hypothesis is that glucocorticoids raise blood pressure by suppression of nitric oxide activity. The study tests this hypothesis by examining whether oral administration of isosorbide mononitrate, which is a nitric oxide donor, changes blood pressure in patients whose blood pressure has gone up after 5 days of treatment with oral hydrocortisone.
Trial website
Nil
Trial related presentations / publications
In preparation
Public notes

Contacts
Principal investigator
Name 50870 0
A/Prof John Kelly
Address 50870 0
Department of Renal Medicine
St George Hospital
50 Montgomery Street.
Kogarah, Sydney.
NSW. 2217
Country 50870 0
Australia
Phone 50870 0
61 2 9350 2622
Fax 50870 0
61 2 9531 0699
Email 50870 0
[email protected]
Contact person for public queries
Name 50871 0
John Kelly
Address 50871 0
Department of Renal Medicine
St George Hospital
50 Montgomery Street.
Kogarah, Sydney.
NSW. 2217
Country 50871 0
Australia
Phone 50871 0
61 2 9350 2622
Fax 50871 0
61 2 9531 0699
Email 50871 0
[email protected]
Contact person for scientific queries
Name 50872 0
John Kelly
Address 50872 0
Department of Renal Medicine
St George Hospital
50 Montgomery Street.
Kogarah, Sydney.
NSW. 2217
Country 50872 0
Australia
Phone 50872 0
61 2 9350 2622
Fax 50872 0
61 2 9531 0699
Email 50872 0
[email protected]

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No Supporting Document Provided



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