Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy
Recruitment status was: Not yet recruiting
Impaired Fasting Glucose
Impaired Glucose Tolerance
|Study Design:||Allocation: Randomized
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|
- Insulin sensitivity [ Time Frame: 7 days per subject; 18 months for entire study ]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.
- Change in active GIP [ Time Frame: 7 days per subject; 18 months for entire study ]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 ]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 ]Change in glucose response during the MTT.
- Change in insulin secretion [ Time Frame: 7 days per subject; 18 months for entire study ]Change in insulin secretion during the MTT.
- Change in disposition index [ Time Frame: 7 days per subject; 18 months for entire study ]Change in AIRg, Si and disposition index (Di) during the FSIVGTT.
|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)|
This arm involves randomization to dex 2.5 mg + sitagliptin 100 mg daily x 7 days followed by MTT and IVGTT on subsequent days.
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
2.5 mg daily x 7 days
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01488279
|United States, Vermont|
|University of Vermont Clinical Research Center|
|South Burlingont, Vermont, United States, 05403|
|Principal Investigator:||Annis M Marney, MD, MSCI||University of Vermont|