PANTHEON-I: The peripheral effects of prednisolone on glucose metabolism, metabolic hormones, insulin sensitivity and insulin secretion in healthy young males and males with metabolic syndrome: a randomised, placebo controlled, double blind, dose-response, parallel group intervention study

Recruitment & Eligibility

Status: Completed

Sex: Male

Target Recruitment: 64

Inclusion Criteria

For all participants:
1. Written informed consent
2. Male caucasian
3. Smoking less than five cigarettes per day and capable of stopping during the trial period

For healthy participants:
1. Healthy as determined by history taking, physical examination, laboratory examinations and Electrocardiogram (ECG):
1.1. Aged 20 to 55 years
1.2. Body Mass Index (BMI) between 20 and 25 kg/m^2
1.3. Fasting glucose less than 5.6 mmol/L and glucose less than 7.8 mmol/L at two hours after intake of 75 g glucose (Oral Glucose Tolerance Test [OGTT])

For participants with metabolic syndrome:
1. Aged 20 to 55 years
2. Waist circumference more than 94 cm
3. Three of following criteria:
3.1. Triglycerides more than 1.7 mmol/L
3.2. High Density Lipoprotein (HDL) cholesterol less than 1.03 mmol/L
3.3. Blood pressure more than 130/85 mmHg
3.4. Fasting glucose level less than 6.1 mmol/L and glucose less than 11.0 mmol/L at two hours after intake of 75 g glucose (OGTT)

Exclusion Criteria

For all participants:
1. Idiosyncrasy/sensitivity to Glucocorticoids (GC)
2. GC use during the last three months prior to first study dose
3. Participation in an investigational drug trial within 90 days prior to the first dose
4. Donation of blood (more than 100 mL) within 90 days prior to the first dose
5. History of or current abuse of drugs or alcohol
6. Serious mental impairment or language problems, i.e., preventing to understand the study protocol/aim

For healthy participants:
1. Presence of a medical disorder
2. Medication use, except for incidental analgesic agents
3. First degree relative with type two diabetes mellitus
4. Performing intensive physical activity more than twice a week

For participants with metabolic syndrome:
1. Serious pulmonary, cardiovascular, hepatic (Alanine Aminotransferase [ALT], Aspartate Aminotransferase [AST] more than 3 x Upper Limit of Normal [ULN]) or renal disease (serum creatinine more than 135 mmol/L)
2. History of cardiovascular disease, such as myocardial infarction, cerebrovascular accident
3. Major psychiatric disorder
4. Depression
5. All diseases that induce changes in the Hypothalamic-Pituitary-Adrenal (HPA) axis
6. Malignant disease
7. All other relevant medical disorders that potentially interfere with this trial*
8. All medication interfering with study drug or interfering with study endpoints/hypotheses*

* the study physician and internist will make an individual assessment per subject whether he is eligible for inclusion

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the effects of a two-week treatment with 7.5 or 30 mg prednisolone daily, compared to placebo, in healthy males and males with the metabolic syndrome on: <br>1. Beta cell function (first phase insulin secretion, corrected for insulin sensitivity, during hyperglycaemic clamp procedure, measured at Day 14<br>2. Whole-body insulin sensitivity (insulin sensitivity index as measured during hyperinsulinaemic-euglycaemic clamp procedure), measured at Day 14

Secondary Outcome Measures

Name	Time	Method
To assess the effects of a two-week treatment with 7.5 or 30 mg prednisolone daily, compared to placebo, in healthy males and males with the metabolic syndrome on: <br>1. Circulating biomarkers (plasma), measured at Day 13<br>2. Insulin-stimulated microvascular function, measured at Day 14<br>3. Blood pressure and haemodynamic parameters, measured at Day 13<br>4. Body fat distribution (Magnetic Resonance Imaging [MRI]), measured at Day 13<br>5. Molecular mechanisms underlying prednisolone effects, measured at Day 14