NCT01620684

The Effects of Cortisol Blockade on Nutritional Sympathetic Nervous System Responsiveness in Overweight and Obese Subjects With Metabolic Syndrome

Status unknown Phase 4 Last updated 8 September 2014

What this trial tests

Phase 4 trial testing metyrapone in Metabolic Syndrome in 24 participants. Status unknown.

Timeline

1 February 2013

Primary endpoint
1 December 2014

Quick facts

Lead sponsor	Baker Heart Research Institute
Phase	Phase 4
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	24
Start date	1 February 2013
Primary completion	1 December 2014
Sites	1 location across Australia

Drugs / interventions tested

• metyrapone (METYRAPONE) — full drug profile →
• placebo

Conditions studied

• Metabolic Syndrome — all drugs for Metabolic Syndrome →
• Obesity — all drugs for Obesity →
• Insulin Resistance — all drugs for Insulin Resistance →

Sponsor

Baker Heart Research Institute

Who can join

Adults 45 to 65, any sex, with Metabolic Syndrome or Obesity. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Nutritional sympathetic nervous system responsiveness
  Time frame: 12-hours
  Effects of acute overnight metyrapone treatment will be studied

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.