NCT00721552

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at P25-P50 for not_applicable diabetes-mellitus

Timeline
Completed

Started Oct 2008

Longer than P75 for not_applicable diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 22, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 24, 2008

Completed
2 months until next milestone

Study Start

First participant enrolled

October 1, 2008

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
Last Updated

July 2, 2012

Status Verified

June 1, 2012

Enrollment Period

3.7 years

First QC Date

July 22, 2008

Last Update Submit

June 28, 2012

Conditions

Keywords

beta-cell functionglucocorticoid-induced diabetesglucocorticoidDPP-4 inhibitorssitagliptindiabetes mellitussteroid diabetesinsulin resistanceinsulin sensitivity

Outcome Measures

Primary Outcomes (1)

  • Glucose tolerance as assessed by the area under the curve for glucose (AUCgluc) during a standardized meal test.

    14 days

Secondary Outcomes (9)

  • Incretin secretion during standardized meal test

    14 days

  • Insulin sensitivity

    14 days

  • Microvascular function: fasting and postprandial

    14 days

  • Body composition, body fat distribution and intra organ fat accumulation

    28 days

  • Molecular mechanisms in subcutaneous adipose tissue

    14 days

  • +4 more secondary outcomes

Study Arms (6)

I

EXPERIMENTAL

prednisolone + sitagliptin

Drug: Sitagliptin 100 mgDrug: Prednisolone 30 mg

II

EXPERIMENTAL

prednisolone + sitagliptin-placebo

Drug: Prednisolone 30 mgDrug: Sitagliptin-placebo

III

EXPERIMENTAL

prednisolone-placebo + sitagliptin

Drug: Sitagliptin 100 mgDrug: Prednisolone-placebo

IV

PLACEBO COMPARATOR

prednisolone-placebo + sitagliptin-placebo

Drug: Sitagliptin-placeboDrug: 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.

Interventions

28 days administration of 100 mg daily

Also known as: Januvia, MK-0431, ATC A10BH01
IIII

14 days administration of 30 mg daily

Also known as: prednison, ATC H02AB06
III

28 days administration once daily

IIIV

14 days administration once daily

IIIIV

Eligibility Criteria

Age35 Years - 65 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VUmc Diabetes Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Related Publications (2)

  • 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.

  • van 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.

MeSH Terms

Conditions

Diabetes MellitusInsulin Resistance

Interventions

Sitagliptin PhosphatePrednisolonePrednisone

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinism

Intervention Hierarchy (Ancestors)

TriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsPyrazinesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsPregnadienediols

Study Officials

  • Michaela Diamant, Md PhD

    VUmc Diabetes Center, Amsterdam, The Netherlands

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. M. Diamant

Study Record Dates

First Submitted

July 22, 2008

First Posted

July 24, 2008

Study Start

October 1, 2008

Primary Completion

June 1, 2012

Study Completion

June 1, 2012

Last Updated

July 2, 2012

Record last verified: 2012-06

Locations