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

ISRCTN ISRCTN78149983
DOI https://doi.org/10.1186/ISRCTN78149983
Secondary identifying numbers DCpred001
Submission date
26/04/2007
Registration date
03/07/2007
Last edited
14/08/2013
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Dr Michaela Diamant
Scientific

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Study information

Study designPANTHEON-I study is a randomised, placebo controlled, double blind, dose-response, parallel group intervention study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Scientific title
Study acronymPANTHEON-I
Study hypothesisGlucocorticoids (GCs), like prednisolone, are the most commonly prescribed anti-inflammatory and immunosuppressive drugs. Although GCs display excellent efficacy in a great number of (auto-immune) diseases, the side effect profile often limits their therapeutical benefit. Major side effects associated with GC treatment include changes in glucose, lipid and protein metabolism, leading to adult onset (a.o.) insulin resistance, glucose intolerance, muscle wasting and dyslipidemia. Currently a renewed interest exists in these poorly understood diabetogenic side effects, with the development of so called 'dissociated glucocorticoid receptor activators', which seem to be lacking these deleterious effects. With this trial, we expect to obtain results that will aid the development of such compounds by a pharmaceutical company that is involved in this study project. This novel class of drugs could become of great importance for the millions of people currently requiring glucocorticoid therapy.

Hypotheses:
What are the effects of a two-week treatment with 7.5 mg prednisolone daily or 30 mg prednisolone daily, versus placebo, on:
1. Various aspects of beta-cell function?
2. Whole-body insulin sensitivity?

This trial is linked to the PANTHEON II study, registered under ISRCTN83991850. Although these trials have the same interventions, the outcomes being looked at are different.
Ethics approval(s)Ethics approval received from the Ethics Committee of the VU University Medical Centre on the 11th October 2007 (ref: 2007/179).
ConditionMetabolic syndrome
InterventionThe effects of a two-week treatment with either prednisolone 7.5 mg daily or prednisolone 30 mg daily versus placebo, will be evaluated.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Prednisolone
Primary outcome measureTo 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:
1. Beta cell function (first phase insulin secretion, corrected for insulin sensitivity, during hyperglycaemic clamp procedure, measured at Day 14
2. Whole-body insulin sensitivity (insulin sensitivity index as measured during hyperinsulinaemic-euglycaemic clamp procedure), measured at Day 14
Secondary outcome measuresTo 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:
1. Circulating biomarkers (plasma), measured at Day 13
2. Insulin-stimulated microvascular function, measured at Day 14
3. Blood pressure and haemodynamic parameters, measured at Day 13
4. Body fat distribution (Magnetic Resonance Imaging [MRI]), measured at Day 13
5. Molecular mechanisms underlying prednisolone effects, measured at Day 14
Overall study start date01/09/2007
Overall study end date01/09/2010

Eligibility

Participant type(s)Patient
Age groupAdult
SexMale
Target number of participants64
Participant inclusion criteriaFor 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)
Participant exclusion criteriaFor 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
Recruitment start date01/09/2007
Recruitment end date01/09/2010

Locations

Countries of recruitment

  • Netherlands

Study participating centre

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Sponsor information

Vrije University Medical Centre (VUMC) (The Netherlands)
Hospital/treatment centre

c/o Dr M. Diamant or Dr R.J. Heine
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

http://www.vumc.nl/english/
ROR logo https://ror.org/00q6h8f30

Funders

Funder type

Hospital/treatment centre

Top Institute Pharma (TIP) (The Netherlands) - a collaborative structure consisting of industrial and academic research teams (www.tipharma.com)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article islet-cell function results 01/04/2013 Yes No
Results article microvascular function results 01/11/2013 Yes No
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