Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism in Males With the Metabolic Syndrome (SPHINX)

June 28, 2012 updated by: M. Diamant, Amsterdam UMC, location VUmc

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
82

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Noord-Holland
      • Amsterdam, Noord-Holland, Netherlands, 1081 HV
        • VUMC Diabetes Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

35 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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)
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: I
prednisolone + sitagliptin
Drug: Sitagliptin 100 mg
28 days administration of 100 mg daily
Other Names:
  • Januvia
  • MK-0431
  • ATC A10BH01
Drug: Prednisolone 30 mg
14 days administration of 30 mg daily
Other Names:
  • prednison
  • ATC H02AB06
Experimental: II
prednisolone + sitagliptin-placebo
Drug: Prednisolone 30 mg
14 days administration of 30 mg daily
Other Names:
  • prednison
  • ATC H02AB06
Drug: Sitagliptin-placebo
28 days administration once daily
Experimental: III
prednisolone-placebo + sitagliptin
Drug: Sitagliptin 100 mg
28 days administration of 100 mg daily
Other Names:
  • Januvia
  • MK-0431
  • ATC A10BH01
Drug: Prednisolone-placebo
14 days administration once daily
Placebo Comparator: IV
prednisolone-placebo + sitagliptin-placebo
Drug: Sitagliptin-placebo
28 days administration once daily
Drug: Prednisolone-placebo
14 days administration once daily
No Intervention: Healthy controls
12 healthy men will be included to assess postprandial microvascular function.
No Intervention: Type 2 diabetic subjects
12 men with type 2 diabetes will be included in order to assess postprandial microvascular function.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Glucose tolerance as assessed by the area under the curve for glucose (AUCgluc) during a standardized meal test.
Time Frame: 14 days
14 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Incretin secretion during standardized meal test
Time Frame: 14 days
14 days
Insulin sensitivity
Time Frame: 14 days
14 days
Microvascular function: fasting and postprandial
Time Frame: 14 days
14 days
Body composition, body fat distribution and intra organ fat accumulation
Time Frame: 28 days
28 days
Molecular mechanisms in subcutaneous adipose tissue
Time Frame: 14 days
14 days
Blood pressure and hemodynamic parameters
Time Frame: 28 days
28 days
Biomarkers such as lipoproteins, adipocytokines, and markers of systemic inflammation
Time Frame: 14 days
14 days
Time to recovery after cessation of the two-week prednisolone treatment
Time Frame: 28 days
28 days
Beta-cell function as determined by hyperglycemic clamp tests and modeling analysis from mixed-meal tests.
Time Frame: 14 days
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Amsterdam UMC, location VUmc

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michaela Diamant, Md PhD, VUmc Diabetes Center, Amsterdam, The Netherlands

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 22, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 24, 2008

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 2, 2012

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2012

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DC2008Pred002
  • Eudract 2008-004985-25

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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