Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by University of Vermont.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by (Responsible Party):
Annis Marney, MD, MSCI, University of Vermont
ClinicalTrials.gov Identifier:
NCT01488279
First received: December 5, 2011
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

The investigators hypothesize that sitagliptin will significantly reduce impairments in insulin secretion and insulin resistance resulting from short-term oral glucocorticoid therapy.


Condition Intervention
Pre-diabetes
Impaired Fasting Glucose
Impaired Glucose Tolerance
Drug: Dexamethasone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy

Resource links provided by NLM:


Further study details as provided by University of Vermont:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    The primary outcome variable will be the difference in the disposition index (DI) determined as the product of the acute insulin response to glucose (AIRg) x the insulin sensitivity index (SI) in subjects on oral dex and either placebo or sitagliptin 100 mg for 1 week. The primary analyses will be an ANCOVA, including baseline responses as a covariate.


Secondary Outcome Measures:
  • Change in active GIP [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    Change in active GIP in response to the MTT.

  • Change in active GLP-1 [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    Change in active GLP-1 in response to the MTT.

  • Change in glucose response [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    Change in glucose response during the MTT.

  • Change in insulin secretion [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    Change in insulin secretion during the MTT.

  • Change in disposition index [ Time Frame: 7 days per subject; 18 months for entire study ] [ Designated as safety issue: No ]
    Change in AIRg, Si and disposition index (Di) during the FSIVGTT.


Estimated Enrollment: 20
Study Start Date: September 2012
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin
This arm involves randomization to dex 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days.
Drug: Dexamethasone
2.5 mg daily x 7 days
Placebo Comparator: Placebo
This arm involves randomization to dex 2.5 mg orally + placebo x 7 days followed by MTT and IVGTT on subsequent days
Drug: Dexamethasone
2.5 mg daily x 7 days

Detailed Description:

The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled parallel arm study comparing insulin secretion and insulin resistance in subjects with impaired fasting glucose on oral glucocorticoid therapy + placebo versus subjects on oral glucocorticoid therapy + sitagliptin. For the oral glucocorticoid therapy, we plan to use dexamethasone (dex) 2.5 mg daily. We chose dex for known glycemic effects, improved compliance, and once daily dosing.

Previous studies have shown that in humans, glucocorticoid-induced insulin resistance develops within 4 hours with infused drug at high dose (methylprednisolone 500 mg x single infusion) and does not change with duration of drug therapy of up to 3 months.10 Furthermore, more modest doses over a short duration (dex 2.0 mg orally daily x 2 days) have been shown to decrease insulin-mediated glucose disposal.11 12 Thus, studying acute effects of oral dex at 2.5 mg daily x 7 days should be more than adequate to achieve impaired glucose-mediated insulin secretion and impaired insulin-mediated glucose disposal.

In order for sitagliptin to have the desired effect, drug should be administered for at least 7 days (5 half-lives plus 40% more for margin of error). We plan to study subjects with impaired fasting glucose or impaired glucose tolerance as they would likely be candidates for DPP-IV therapy in the future and would be likely to have impaired insulin secretion and impaired glucose disposal amenable to DPP-IV therapy.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women
  • impaired fasting glucose
  • We will stratify for weight and age.

Exclusion Criteria:

  • Known Type 2 DM
  • Severe disease preventing participation in study
  • On chronic steroids for any reason
  • Already taking DPP-4 inhibitor
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488279

Contacts
Contact: Annis M Marney, MD, MSCI 802-847-4157 annis.marney@uvm.edu
Contact: Angela Ferro, RN 802-847-8908 angela.ferro@vtmednet.org

Locations
United States, Vermont
University of Vermont Clinical Research Center Not yet recruiting
South Burlingont, Vermont, United States, 05403
Principal Investigator: Annis M Marney, MD, MSCI         
Sponsors and Collaborators
University of Vermont
Investigators
Principal Investigator: Annis M Marney, MD, MSCI University of Vermont
  More Information

No publications provided

Responsible Party: Annis Marney, MD, MSCI, Assistant Professor of Medicine, University of Vermont
ClinicalTrials.gov Identifier: NCT01488279     History of Changes
Other Study ID Numbers: MISP 39681
Study First Received: December 5, 2011
Last Updated: July 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Vermont:
Pre-diabetes
Impaired fasting glucose
Impaired glucose tolerance
Steroid-induced hyperglycemia

Additional relevant MeSH terms:
Glucose Intolerance
Prediabetic State
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Dexamethasone
Glucocorticoids
Sitagliptin
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Hypoglycemic Agents
Incretins
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014