Diabetes MellitusSPHINXNCT00721552
Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism in Males With the Metabolic Syndrome
A study testing Sitagliptin 100 mg and Prednisolone 30 mg in people with Diabetes Mellitus and Steroid Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
The investigators will assess whether the DPP-inhibitor sitagliptin will ameliorate glucocorticoid-induced impairment of glucose metabolism and beta-cell dysfunction and thus could be used as a prophylaxis for glucocorticoid-induced diabetes. Read more about this study
- Who is it for?
- Ages 35 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Steroid Diabetes, Glucocorticoid-induced Diabetes
- What is being tested?
- Sitagliptin 100 mg and Prednisolone 30 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2008to Jun 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Caucasian males
- Modified from IDF criteria for the metabolic syndrome:
- Waist circumference ≥ 94 cm
- And at least 2 or more of the following criteria:
- TG ≥ 1.7 mmol/L
- HDL cholesterol < 1.03 mmol/L
- Blood pressure >130/85 mmHg (average of three measurements) or treatment of previously diagnosed hypertension
- Fasting plasma glucose level (FPG) ≥ 5.6 mmol/L (but no diabetes)
Who cannot join
- An allergic or anaphylactic reaction to prednisolone treatment in the past
- Clinically relevant history or presence of any medical disorder, which are mentioned in the Summary of Product Characteristics (SPC) as contraindication for the use of prednisolone
- Glucocorticosteroid use during the last three months prior to the first dose
- Participation in an investigational drug trial within 90 days prior to the first dose
- Donation of blood ( > 100 mL) within 90 days prior to the first dose
- History of or current abuse of drugs or alcohol (>14 U/week)
Show all 17Show fewer
- Use of grapefruit products during the study period
- Recent changes in weight and/or physical activity
- Serious mental impairment or language problems i.e. preventing to understand the study protocol/aim
- Diabetes mellitus (defined as FPG ≥ 7.0 mmol/l and/or 2hPG ≥ 11.1 mmol/l)
- Serious pulmonary, cardiovascular, hepatic (ALT, AST more than 3x ULN) or renal disease (serum creatinine > 135 micromol/L)
- History of cardiovascular disease, such as myocardial infarction, cerebrovascular accident.
- Major psychiatric disorder, depression
- All diseases that induce changes in the hypothalamic-pituitary-adrenal (HPA) axis
- Malignant disease
- All other relevant medical disorders that potentially interfere with this trial.
- All medication interfering with study drug or interfering with study endpoints/hypotheses
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism and Beta-Cell Dysfunction in Males With the Metabolic Syndrome X: A Randomized, Placebo-controlled, Double-blind Intervention Study With a 2x2 Factorial Design
The investigators will assess whether the DPP-inhibitor sitagliptin will ameliorate glucocorticoid-induced impairment of glucose metabolism and beta-cell dysfunction and thus could be used as a prophylaxis for glucocorticoid-induced diabetes. Therefore the investigators will administer in males with the metabolic syndrome 30 mg prednisolone daily for two weeks and give simultaneously sitagliptin 100 mg daily. Subjects will undergo at baseline and after two weeks of treatment several tests to assess changes in glucose metabolism.
Read the detailed description
The investigators will conduct a randomized, placebo-controlled, double-blind, 2x2 factorial-designed intervention trial. The pharmacological intervention for prednisolone/prednisolone-placebo is 14 days and for sitagliptin/sitagliptin-placebo 28 days. Subjects fulfilling the IDF criteria26 for the metabolic syndrome (aged 35-65; n=60) will be randomized to one of four groups: I) prednisolone 30 mg and sitagliptin 100 mg daily; II) prednisolone 30 mg and sitagliptin-placebo daily; III) prednisolone-placebo and sitagliptin 100 mg daily; IV) prednisolone-placebo and sitagliptin-placebo daily. Before and at day 14 of treatment subjects will undergo a standardized mixed-meal test in order to assess glucose disposal and beta-cell function (by modeling analysis). During these meal tests, plasma concentrations of (total and active) GLP-1, GIP, glucagon and additional biomarkers will be assessed. A combined hyperglycemic-euglycemic clamp will be performed at baseline and at day 13 of treatment to assess insulin sensitivity and insulin secretion. During the euglycemic clamp adipose tissue and muscle biopsies will be obtained, both in fasting and under hyperinsulinemic conditions. At baseline and at day 28 of treatment, a 7-point OGTT will be performed to assess time to restoration of glycemic control. Body composition, body fat distribution and liver fat content, measured by respectively bio-impedance analysis and magnetic resonance imaging/spectroscopy (MRI/MRS), will be assessed at baseline and after 28 days of treatment. Blood pressure will be assessed at baseline and after two weeks of treatment. Microvascular function will be assessed with capillary videomicroscopy both at baseline and after two weeks of treatment.
- Being tested
- Sitagliptin 100 mg, Prednisolone 30 mg, Sitagliptin-placebo, Prednisolone-placebo
- Keywords
- beta-cell function, glucocorticoid-induced diabetes, glucocorticoid, DPP-4 inhibitors, sitagliptin, diabetes mellitus, steroid diabetes, insulin resistance, insulin sensitivity
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sitagliptin 100 mgDrug
Also called Januvia, MK-0431, ATC A10BH01
28 days administration of 100 mg daily
Prednisolone 30 mgDrug
Also called prednison, ATC H02AB06
14 days administration of 30 mg daily
Sitagliptin-placeboDrug
28 days administration once daily
Prednisolone-placeboDrug
14 days administration once daily
| Study group | Role | What they receive |
|---|---|---|
| I | Experimental | prednisolone + sitagliptin Receives: Drug: Sitagliptin 100 mg; Drug: Prednisolone 30 mg |
| II | Experimental | prednisolone + sitagliptin-placebo Receives: Drug: Prednisolone 30 mg; Drug: Sitagliptin-placebo |
| III | Experimental | prednisolone-placebo + sitagliptin Receives: Drug: Sitagliptin 100 mg; Drug: Prednisolone-placebo |
| IV | Placebo comparator | prednisolone-placebo + sitagliptin-placebo Receives: Drug: Sitagliptin-placebo; Drug: Prednisolone-placebo |
| Healthy controls | No intervention | 12 healthy men will be included to assess postprandial microvascular function. |
| Type 2 diabetic subjects | No intervention | 12 men with type 2 diabetes will be included in order to assess postprandial microvascular function. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucose tolerance as assessed by the area under the curve for glucose (AUCgluc) during a standardized meal test.
Measured: 14 days
Secondary outcomes (9)
Incretin secretion during standardized meal test
Measured: 14 days
Insulin sensitivity
Measured: 14 days
Microvascular function: fasting and postprandial
Measured: 14 days
Body composition, body fat distribution and intra organ fat accumulation
Measured: 28 days
Molecular mechanisms in subcutaneous adipose tissue
Measured: 14 days
Blood pressure and hemodynamic parameters
Measured: 28 days
Biomarkers such as lipoproteins, adipocytokines, and markers of systemic inflammation
Measured: 14 days
Time to recovery after cessation of the two-week prednisolone treatment
Measured: 28 days
Beta-cell function as determined by hyperglycemic clamp tests and modeling analysis from mixed-meal tests.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2008 (estimated)
- Study startOct 2008
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Diamant, Amsterdam UMC, location VUmc
- Investigators
- Michaela Diamant, Md PhD, Principal investigator, VUmc Diabetes Center, Amsterdam, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00721552
- Sponsor's protocol ID
- DC2008Pred002
- Other IDs
- Eudract 2008-004985-25
- Acronym
- SPHINX
- Status last verified
- Jun 2012
- First submitted
- 22 Jul 2008
- Last updated
- 2 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
van Genugten RE, van Raalte DH, Muskiet MH, Heymans MW, Pouwels PJ, Ouwens DM, Mari A, Diamant M. Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of glucocorticoids in men with the metabolic syndrome? A randomized controlled trial. Eur J Endocrinol. 2014 Feb 4;170(3):429-39. doi: 10.1530/EJE-13-0610. Print 2014 Mar.
PubMed 24297090van Genugten RE, Serne EH, Heymans MW, van Raalte DH, Diamant M. Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes. Diabetologia. 2013 Mar;56(3):583-7. doi: 10.1007/s00125-012-2783-y. Epub 2012 Nov 24.
PubMed 23178932
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism and Beta-Cell Dysfunction in Males With the Metabolic Syndrome X: A Randomized, Placebo-controlled, Double-blind Intervention Study With a 2x2 Factorial Design
- ClinicalTrials.gov ID
- NCT00721552
- Acronym / sponsor ID
- SPHINX / DC2008Pred002
- Keywords
- beta-cell function, glucocorticoid-induced diabetes, glucocorticoid, DPP-4 inhibitors, sitagliptin, diabetes mellitus, steroid diabetes, insulin resistance
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 24 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will assess whether the DPP-inhibitor sitagliptin will ameliorate glucocorticoid-induced impairment of glucose metabolism and beta-cell dysfunction and thus could be used as a prophylaxis for glucocorticoid-induced diabetes. Therefore the investigators will administer in males with the metabolic syndrome 30 mg prednisolone daily for two weeks and give simultaneously sitagliptin 100 mg daily. Subjects will undergo at baseline and after two weeks of treatment several tests to assess changes in glucose metabolism.
Detailed description
The investigators will conduct a randomized, placebo-controlled, double-blind, 2x2 factorial-designed intervention trial. The pharmacological intervention for prednisolone/prednisolone-placebo is 14 days and for sitagliptin/sitagliptin-placebo 28 days. Subjects fulfilling the IDF criteria26 for the metabolic syndrome (aged 35-65; n=60) will be randomized to one of four groups: I) prednisolone 30 mg and sitagliptin 100 mg daily; II) prednisolone 30 mg and sitagliptin-placebo daily; III) prednisolone-placebo and sitagliptin 100 mg daily; IV) prednisolone-placebo and sitagliptin-placebo daily. Before and at day 14 of treatment subjects will undergo a standardized mixed-meal test in order to assess glucose disposal and beta-cell function (by modeling analysis). During these meal tests, plasma concentrations of (total and active) GLP-1, GIP, glucagon and additional biomarkers will be assessed. A combined hyperglycemic-euglycemic clamp will be performed at baseline and at day 13 of treatment to assess insulin sensitivity and insulin secretion. During the euglycemic clamp adipose tissue and muscle biopsies will be obtained, both in fasting and under hyperinsulinemic conditions. At baseline and at day 28 of treatment, a 7-point OGTT will be performed to assess time to restoration of glycemic control. Body composition, body fat distribution and liver fat content, measured by respectively bio-impedance analysis and magnetic resonance imaging/spectroscopy (MRI/MRS), will be assessed at baseline and after 28 days of treatment. Blood pressure will be assessed at baseline and after two weeks of treatment. Microvascular function will be assessed with capillary videomicroscopy both at baseline and after two weeks of treatment.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| I | Experimental | Drug: Sitagliptin 100 mg, Drug: Prednisolone 30 mgprednisolone + sitagliptin |
| II | Experimental | Drug: Prednisolone 30 mg, Drug: Sitagliptin-placeboprednisolone + sitagliptin-placebo |
| III | Experimental | Drug: Sitagliptin 100 mg, Drug: Prednisolone-placeboprednisolone-placebo + sitagliptin |
| IV | Placebo comparator | Drug: Sitagliptin-placebo, Drug: Prednisolone-placeboprednisolone-placebo + sitagliptin-placebo |
| Healthy controls | No intervention | –12 healthy men will be included to assess postprandial microvascular function. |
| Type 2 diabetic subjects | No intervention | –12 men with type 2 diabetes will be included in order to assess postprandial microvascular function. |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Caucasian males
- Modified from IDF criteria for the metabolic syndrome:
- And at least 2 or more of the following criteria:
Key exclusion criteria (17 listed)
- An allergic or anaphylactic reaction to prednisolone treatment in the past
- Clinically relevant history or presence of any medical disorder, which are mentioned in the Summary of Product Characteristics (SPC) as contraindication for the use of prednisolone
- Glucocorticosteroid use during the last three months prior to the first dose
- Participation in an investigational drug trial within 90 days prior to the first dose
- Donation of blood ( > 100 mL) within 90 days prior to the first dose
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sitagliptin 100 mgAlso: Januvia, MK-0431, ATC A10BH0128 days administration of 100 mg daily | Drug | I, III |
| Prednisolone 30 mgAlso: prednison, ATC H02AB0614 days administration of 30 mg daily | Drug | I, II |
| Sitagliptin-placebo28 days administration once daily | Drug | II, IV |
| Prednisolone-placebo14 days administration once daily | Drug | III, IV |
Primary outcome
Glucose tolerance as assessed by the area under the curve for glucose (AUCgluc) during a standardized meal test.
Time frame: 14 days
9 secondary outcomes
Incretin secretion during standardized meal test
Time frame: 14 days
Insulin sensitivity
Time frame: 14 days
Microvascular function: fasting and postprandial
Time frame: 14 days
Body composition, body fat distribution and intra organ fat accumulation
Time frame: 28 days
Molecular mechanisms in subcutaneous adipose tissue
Time frame: 14 days
Blood pressure and hemodynamic parameters
Time frame: 28 days
Biomarkers such as lipoproteins, adipocytokines, and markers of systemic inflammation
Time frame: 14 days
Time to recovery after cessation of the two-week prednisolone treatment
Time frame: 28 days
Beta-cell function as determined by hyperglycemic clamp tests and modeling analysis from mixed-meal tests.
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2012.
- Derived from this study: PubMed 24297090van Genugten RE, van Raalte DH, Muskiet MH, Heymans MW, Pouwels PJ, Ouwens DM, Mari A, Diamant M. Does dipeptidyl peptidase-4 inhibition prevent the diabetogenic effects of glucocorticoids in men with the metabolic syndrome? A randomized controlled trial. Eur J Endocrinol. 2014 Feb 4;170(3):429-39. doi: 10.1530/EJE-13-0610. Print 2014 Mar.
- Derived from this study: PubMed 23178932van Genugten RE, Serne EH, Heymans MW, van Raalte DH, Diamant M. Postprandial microvascular function deteriorates in parallel with gradual worsening of insulin sensitivity and glucose tolerance in men with the metabolic syndrome or type 2 diabetes. Diabetologia. 2013 Mar;56(3):583-7. doi: 10.1007/s00125-012-2783-y. Epub 2012 Nov 24.
Related trials for Diabetes Mellitus
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michaela Diamant, Md PhD principal investigator
VUmc Diabetes Center, Amsterdam, The Netherlands
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sitagliptin 100 mg and Prednisolone 30 mg in people with Diabetes Mellitus and Steroid Diabetes, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glucose tolerance as assessed by the area under the curve for glucose (AUCgluc) during a standardized meal test. (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00721552, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2012.