Condition category
Nutritional, Metabolic, Endocrine
Date applied
26/04/2007
Date assigned
03/07/2007
Last edited
14/08/2013
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Michaela Diamant

ORCID ID

Contact details

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

DCpred001

Study information

Scientific title

Acronym

PANTHEON-I

Study hypothesis

Glucocorticoids (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

Ethics approval received from the Ethics Committee of the VU University Medical Centre on the 11th October 2007 (ref: 2007/179).

Study design

PANTHEON-I study is a randomised, placebo controlled, double blind, dose-response, parallel group intervention study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Metabolic syndrome

Intervention

The effects of a two-week treatment with either prednisolone 7.5 mg daily or prednisolone 30 mg daily versus placebo, will be evaluated.

Intervention type

Drug

Phase

Not Specified

Drug names

Prednisolone

Primary outcome measures

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:
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 measures

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:
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 trial start date

01/09/2007

Overall trial end date

01/09/2010

Reason abandoned

Eligibility

Participant 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)

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

64

Participant 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

Recruitment start date

01/09/2007

Recruitment end date

01/09/2010

Locations

Countries of recruitment

Netherlands

Trial participating centre

De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Sponsor information

Organisation

Vrije University Medical Centre (VUMC) (The Netherlands)

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

http://www.vumc.nl/english/

Funders

Funder type

Hospital/treatment centre

Funder name

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

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2013 islet-cell function results in http://www.ncbi.nlm.nih.gov/pubmed/23164480
2. 2013 microvascular function results in http://www.ncbi.nlm.nih.gov/pubmed/23933953

Publication citations

  1. Microvascular function results

    van Raalte DH, Diamant M, Ouwens DM, Ijzerman RG, Linssen MM, Guigas B, Eringa EC, Serné EH, Glucocorticoid treatment impairs microvascular function in healthy men in association with its adverse effects on glucose metabolism and blood pressure: a randomised controlled trial., Diabetologia, 2013, 56, 11, 2383-2391, doi: 10.1007/s00125-013-3016-8.

  2. van Raalte DH, Kwa KA, van Genugten RE, Tushuizen ME, Holst JJ, Deacon CF, Karemaker JM, Heine RJ, Mari A, Diamant M, Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?, Metab. Clin. Exp., 2013, 62, 4, 568-577, doi: 10.1016/j.metabol.2012.10.007.

Additional files

Editorial Notes