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

NCT ID: NCT01488279

Last Updated: 2018-03-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-09-30

Study Completion Date

2015-12-31

Brief Summary

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

Detailed Description

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The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled parallel arm crossover 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.

A total of 10 participants were enrolled in this study. Participants were given 2.5 mg dexamethasone daily plus either placebo tablet or sitagliptin daily for 8 days with a washout period prior to crossover. The order of study drug administration was randomized. Participants underwent blood sampling, mixed meal testing (MMT), and intravenous glucose tolerance testing (IVGTT) before and after each study period.

Conditions

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Pre-diabetes Impaired Fasting Glucose Impaired Glucose Tolerance

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Double blind, placebo controlled crossover study
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Drugs were dispensed by the pharmacy with both the patient and investigator blinded

Study Groups

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Dexamethasone 2.5mg and Sitagliptin100mg

Participants received Dexamethasone 2.5 mg plus Sitagliptin 100 mg daily for 8 days

Group Type ACTIVE_COMPARATOR

Dexamethasone 2.5 mg and Sitagliptin 100 mg

Intervention Type DRUG

Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days

Dexamethasone 2.5 mg and placebo tablet

Intervention Type DRUG

Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days

Dexamethasone 2.5mg and placebo tablet

Participants received Dexamethasone 2.5 mg plus Sitagliptin-matched placebo tablet daily for 8 days.

Group Type PLACEBO_COMPARATOR

Dexamethasone 2.5 mg and Sitagliptin 100 mg

Intervention Type DRUG

Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days

Dexamethasone 2.5 mg and placebo tablet

Intervention Type DRUG

Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days

Interventions

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Dexamethasone 2.5 mg and Sitagliptin 100 mg

Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days

Intervention Type DRUG

Dexamethasone 2.5 mg and placebo tablet

Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days

Intervention Type DRUG

Other Intervention Names

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Sitagliptin Placebo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Vermont

OTHER

Sponsor Role lead

Responsible Party

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Annis Marney, MD, MSCI

Assistant Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Annis M Marney, MD, MSCI

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Locations

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University of Vermont Clinical Research Center

South Burlington, Vermont, United States

Site Status

Countries

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United States

Other Identifiers

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MISP 39681

Identifier Type: -

Identifier Source: org_study_id

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