Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000739516
Ethics application status
Approved
Date submitted
29/06/2015
Date registered
17/07/2015
Date last updated
21/06/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Correlation between cortisol hormone levels and cardiovascular risk in healthy adults
Scientific title
Effects of variability in cortisol homeostasis on insulin sensitivity and cardiovascular risk in healthy adults
Secondary ID [1] 286995 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
insulin sensitivity 295456 0
cardiovascular disease 295457 0
Condition category
Condition code
Metabolic and Endocrine 295712 295712 0 0
Diabetes
Cardiovascular 295714 295714 0 0
Coronary heart disease

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
50 participants aged >40 years living independently in the community will be recruited.
Assessment of insulin sensitivity and secretion and vascular function:
Insulin sensitivity and secretion: Estimates of insulin sensitivity and secretion will be attained from measurements of glucose, insulin and C-peptide before and over two hours after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat) using the Matsuda index and C-peptide deconvolution respectively. Glomerular filtration rate will be measured at baseline.
Arterial stiffness: Arterial stiffness (augmentation index (AI) and pulse wave velocity (PWV)) will be assessed by Pulse-Wave Analysis from the radial, carotid and femoral arteries using a SphygmoCor device (AtCor Medical, West Ryde, NSW, Australia). AI will be assessed before and every 30 minutes post meal for 2 hours and pulse wave velocity will be done twice- before and 90 minutes after meal in a standardized orde
Endothelial function: Endothelial function will be estimated using an Endo-PAT 2000 (Itamar Medical, Caesarea, Israel) before and at 2 hours after a mixed-meal.
Arginine metabolomics: Plasma concentrations of 7 key compounds (arginine, ADMA, symmetric dimethylarginine, mono-methyl arginine, homoarginine, citrulline and ornithine) will be measured fasting and 2-hours postprandially by ultra-performance liquid-chromatography (UPLC) with detection by quadrupole time-of-flight mass spectrometry.
Assessment of cortisol homeostasis and body composition:
Twenty-four hour production: In the 24 hours before visit 2 participants will collect urine for quantification of free cortisol excretion (measure of overall cortisol production).
Synacthen test: Serum cortisol concentration will be measured before and then 30 and 60 minutes after administration of 1 mcg Synacthen (ACTH1-24, Novartis Pharmaceuticals, NSW, Australia) intravenously (measure of HPA hyperactivity).
Salivary cortisol: Participants will be asked to collect salivary samples at 08.00, 08.30, 12.00 and 21.00 for estimation of cortisol (to assess the circadian variation in cortisol secretion)
Body composition: Lean body mass, fat mass and central abdominal fat will be measured by DEXA.
Intervention code [1] 292205 0
Not applicable
Comparator / control treatment
not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 295425 0
The primary end point is the difference in reactive hyperaemia index measured using endo-PAT 2000 device between high and low cortisol responders
Timepoint [1] 295425 0
Reactive hyperaemia index will be assessed before and 2 hours after meal in all participants
Secondary outcome [1] 315564 0
insulin sensitivity using matsuda index
Timepoint [1] 315564 0
Insulin and glucose levels will be checked fasting and at 30, 60, 90 and 120 minutes after a mixed-meal and insulin sensitivity calculated using matsuda index
Secondary outcome [2] 315693 0
Augmentation index
Timepoint [2] 315693 0
Augmentation index, a validated marker of systemic arterial stiffness will be assessed fasting and at 30, 60, 90 and 120 minutes post mixed-meal using a sphygmacor hyaemodynamic device
Secondary outcome [3] 315694 0
Pulse wave velocity
Timepoint [3] 315694 0
Pulse wave velocity will be assessed fasting and at 90 minutes post mixed-meal using a sphygmacor haemodynamic device
Secondary outcome [4] 315695 0
Arginine metabolism
Timepoint [4] 315695 0
Arginine and its metabolites (citrulline, homoarginine, ornithine), and inhibitors of nitric oxide synthase (ADMA, MMA and SDMA) will be estimated fasting and at 2 hours post mixed meal
Secondary outcome [5] 315696 0
insulin secretion
Timepoint [5] 315696 0
Insulin secretion will be assessed using C-peptide deconvolution method from glucose, insulin and C-peptide levels estimated fasting and at half an hour intervals for 2 hours after a mixed meal

Eligibility
Key inclusion criteria
Age >40 years and living independently in the community
Minimum age
41 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
History of pituitary or adrenal adenoma, taking oral glucocorticoids within the last month, current Atrial fibrillation, Raynaud’s phenomenon, Rheumatoid arthritis, taking oral oestrogen (e.g oral contraceptive or hormone replacement therapy), severe asthma (hospital admission in the last 5 years)

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Simple linear regression analysis of the relationship between measures of cortisol homeostasis and cardio-metabolic endpoints will be performed. Comparison of cardio-metabolic endpoints in participants with a peak cortisol response to Synacthen above (high responders) versus below (low responders) the median will be undertaken. The primary end point is the difference in reactive hyperaemia index between high and low cortisol responders. A sample size of 50 participants has 79% power to detect a difference of 0.4 at the two-tailed 0.05 significance level, assuming a SD of 0.5. It is highly clinically relevant; a difference in RHI of 0.1 was independently associated with a 23% difference in cardiac events during a mean follow-up of 2.8 years

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
22/06/2015
Actual
22/06/2015
Date of last participant enrolment
Anticipated
13/11/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 3976 0
Repatriation Hospital - Daw Park
Recruitment postcode(s) [1] 9884 0
5041 - Daw Park

Funding & Sponsors
Funding source category [1] 291551 0
Other Collaborative groups
Name [1] 291551 0
Diabetes Australia Research Trust
Country [1] 291551 0
Australia
Primary sponsor type
Individual
Name
Assoc Prof Morton Burt
Address
Southern Adelaide Diabtes and Endocrine Services
B-Block, Repatriation General Hospital, Daws Road, Daw Park, SA, Australia- 5041
Country
Australia
Secondary sponsor category [1] 290228 0
Individual
Name [1] 290228 0
Dr Anjana Radhakutty
Address [1] 290228 0
Southern Adelaide Diabetes and Endocrine Services, B-Block, Repatriation General Hospital, Daws Road, Daw Park, SA -5041
Country [1] 290228 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293093 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 293093 0
Ethics committee country [1] 293093 0
Australia
Date submitted for ethics approval [1] 293093 0
05/09/2014
Approval date [1] 293093 0
13/11/2014
Ethics approval number [1] 293093 0
389.14

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 58438 0
A/Prof Morton Burt
Address 58438 0
Southern Adelaide Diabetes and Endocrine Services, B-Block, Repatriation General Hospital, Daws Road, Daw Park, SA 5041
Country 58438 0
Australia
Phone 58438 0
+61 8 82751094
Fax 58438 0
+61 8 82751215
Email 58438 0
[email protected]
Contact person for public queries
Name 58439 0
Morton Burt
Address 58439 0
Southern Adelaide Diabetes and Endocrine Services, B-Block, Repatriation General Hospital, Daws Road, Daw Park, SA 5041
Country 58439 0
Australia
Phone 58439 0
+61 8 82751094
Fax 58439 0
+61 8 82751215
Email 58439 0
[email protected]
Contact person for scientific queries
Name 58440 0
Morton Burt
Address 58440 0
Southern Adelaide Diabetes and Endocrine Services, B-Block, Repatriation General Hospital, Daws Road, Daw Park, SA 5041
Country 58440 0
Australia
Phone 58440 0
+61 8 82751094
Fax 58440 0
+61 8 82751215
Email 58440 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

Documents added manually
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