Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
DCpred001
Study information
Scientific title
Acronym
PANTHEON-II
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. 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
Ethics approval received from the Ethics Committee of the VU University Medical Centre on the 11th October 2007 (ref: 2007/179).
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
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 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 trial start date
01/09/2007
Overall trial end date
01/09/2010
Reason abandoned (if study stopped)
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
60
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
Department of Endocrinology/Diabetes Centre
Amsterdam
1081 HV
Netherlands
Sponsor information
Organisation
Vrije University Medical Centre (VUMC) (The Netherlands)
Sponsor details
c/o Dr M. Diamant and Dr R.J. Heine
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Industry
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
Basic results (scientific)
Publication list
1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21562755
2. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23386653
Publication citations
-
Results
van Raalte DH, Brands M, van der Zijl NJ, Muskiet MH, Pouwels PJ, Ackermans MT, Sauerwein HP, Serlie MJ, Diamant M, Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial., Diabetologia, 2011, 54, 8, 2103-2112, doi: 10.1007/s00125-011-2174-9.
-
Results
Brands M, van Raalte DH, João Ferraz M, Sauerwein HP, Verhoeven AJ, Aerts JM, Diamant M, Serlie MJ, No difference in glycosphingolipid metabolism and mitochondrial function in glucocorticoid-induced insulin resistance in healthy men., J. Clin. Endocrinol. Metab., 2013, 98, 3, 1219-1225, doi: 10.1210/jc.2012-3266.