PANTHEON-II: 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 | ISRCTN83991850 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN83991850 |
| Secondary identifying numbers | DCpred001 |
- Submission date
- 08/05/2007
- Registration date
- 03/07/2007
- Last edited
- 17/04/2019
- 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 of protocol
Not provided at time of registration
Contact information
Dr Michaela Diamant
Scientific
Scientific
Department of Endocrinology/Diabetes Centre
Vrije University Medical Centre
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Study information
| Study design | PANTHEON-II study is a randomised, placebo controlled, double blind, dose-response, parallel group intervention study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | PANTHEON-II: 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 |
| Study acronym | PANTHEON-II |
| Study objectives | 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. Metabolic fluxes such as endogenous glucose production, rate of lipolysis and proteolysis? 2. Peripheral and hepatic insulin sensitivity? This trial is linked to the PANTHEON I study, registered under ISRCTN78149983. 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). |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Prednisolone |
| Primary outcome measure | 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. Metabolic fluxes of glucose-, fat- and protein metabolism (rates will be calculated using Steele's equation), measured at Day 14 2. Hepatic and peripheral insulin sensitivity (insulin sensitivity index measured during a two-step 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 14 2. Body composition, measured at Day 13 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 date | 01/09/2007 |
| Completion date | 01/09/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Male |
| Target number of participants | 60 |
| Key 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) |
| Key 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 |
| Date of first enrolment | 01/09/2007 |
| Date of final enrolment | 01/09/2010 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Department of Endocrinology/Diabetes Centre
Amsterdam
1081 HV
Netherlands
1081 HV
Netherlands
Sponsor information
Vrije University Medical Centre (VUMC) (The Netherlands)
Hospital/treatment centre
Hospital/treatment centre
c/o Dr M. Diamant and Dr R.J. Heine
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
| Website | http://www.vumc.nl/english/ |
|---|---|
"ROR" |
https://ror.org/00q6h8f30 |
Funders
Funder type
Industry
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 share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/08/2011 | Yes | No | |
| Results article | results | 01/03/2013 | Yes | No | |
| Results article | results | 01/07/2018 | 17/04/2019 | Yes | No |
Editorial Notes
17/04/2019: Publication reference added.
