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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01620684




Registration number
NCT01620684
Ethics application status
Date submitted
12/06/2012
Date registered
15/06/2012
Date last updated
9/09/2014

Titles & IDs
Public title
Cortisol and Nutritional Sympathetic Responsiveness
Scientific title
The Effects of Cortisol Blockade on Nutritional Sympathetic Nervous System Responsiveness in Overweight and Obese Subjects With Metabolic Syndrome
Secondary ID [1] 0 0
Heart Foundation G11M5892
Secondary ID [2] 0 0
Metyrapone
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metabolic Syndrome 0 0
Obesity 0 0
Insulin Resistance 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - metyrapone
Treatment: Drugs - placebo

Active comparator: metyrapone - Overnight metyrapone treatment (total dose of 30 mg/kg)

Placebo comparator: sugar pill - Overnight treatment with placebo capsules


Treatment: Drugs: metyrapone
Overnight treatment (15 mg/kg at midnight and 15 mg/kg at 6 am)

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

Outcomes
Primary outcome [1] 0 0
Nutritional sympathetic nervous system responsiveness
Timepoint [1] 0 0
12-hours
Secondary outcome [1] 0 0
insulin sensitivity
Timepoint [1] 0 0
12 hours

Eligibility
Key inclusion criteria
* un-medicated,
* overweight or obese subjects (12 men and 12 postmenopausal women),
* weight-stable,
* non-smoking,
* aged 45-65 years
* will be recruited on the basis of having > 3 MetS criteria as per the newly harmonized definition.
* elevated waist circumference will be defined as > 102 cm in men and > 88 cm in women.
* all subjects will also be insulin resistant (HOMA index > 2.5 and/or euglycaemic hyperinsulinemic clamp derived M/I value < 8 mg per kg fat free mass per minute per mU/L x 100).
Minimum age
45 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* adrenocortical insufficiency,
* pituitary dysfunction or tumour,
* sleep apnoea treated with CPAP,
* cardiovascular disease (previous MI, angina, stroke, heart failure, secondary hypertension),
* renal or hepatic disease (serum creatinine > 0.2 mmol/L; > 1 proteinuria on dipstick; alanine transferase > 2.5 times upper limit of normal, active liver disease) or
* diseases which may affect measured parameters (e.g. thyroid, Cushing's or Addison's diseases).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Heart Centre, Alfred Hospital - Prahran, Melbourne
Recruitment postcode(s) [1] 0 0
3181 - Prahran, Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Baker Heart Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This project will examine whether short-term (over a 12-hour period) pharmacological lowering of the stress hormone 'cortisol' improves the nervous system response to food intake in overweight or obese individuals who have metabolic syndrome.

The investigators know from our previous research that overweight/obese persons who are insulin resistant, have a blunted sympathetic nervous response to carbohydrate ingestion. This means that they are less able to dissipate energy from caloric intake, which would favour the maintenance of the obese state. Cortisol adversely impacts on insulin action and transport into the brain and cortisol levels are often elevated in persons with central (abdominal) obesity.

A randomized, double-blind, placebo controlled, cross-over design will be used to compare the effects of overnight treatment with metyrapone (15 mg/kg at midnight and 15 mg/kg at 6 am) versus placebo on sympathetic nervous system activity in response to a standard 75-g oral sugar (glucose) tolerance test. A 2 week washout will separate treatments.

Metyrapone is a drug that reversibly inhibits the enzyme 11beta-hydroxylase, and therefore the production of cortisol. It is used clinically to test the activity of the adrenal gland (the key site of cortisol production) and the pituitary gland. The investigators anticipate that at the dosage used, it will lower blood cortisol concentration by 44 to 64% during the experimental morning.

The study protocol comprises two screening visits and two experimental mornings. Key procedures will include:

* Assessment of insulin action (sensitivity) using the gold standard 'clamp' method.
* Measurement of sympathetic nervous system activity by both biochemical methods (isotope dilution which provides a measure of the apparent rate of release of 'noradrenaline'-the key neurotransmitter in the sympathetic nervous system) and direct intra-neuronal nerve recordings from the peroneal nerve in the lower leg.
* Indirect calorimetry to assess resting metabolic rate and the response to sugar ingestion.
* DEXA scan to quantify fat and lean mass.
* Assessment of arterial elasticity and calf blood flow by non-invasive methods.
* A standard 75g oral sugar tolerance test.

The results will provide important new information regarding the role of cortisol on nervous system function in overweight/obese individuals.
Trial website
https://clinicaltrials.gov/study/NCT01620684
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Nora E Straznicky, PhD MPH
Address 0 0
Baker IDI Heart & Diabetes Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nora E Straznicky, PhD MPH
Address 0 0
Country 0 0
Phone 0 0
61 3 8532 1371
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01620684