Sitagliptin in Type I Diabetic Patients

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of sitagliptin on overall blood glucose concentrations in Type I Diabetic subjects. The study also aims to evaluate post meal glucagon concentrations in Type I Diabetic subjects (a possible mechanism of reduced blood glucose concentrations) and indices of oxidation stress in the plasma of these subjects.

Detailed Description
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The hypothesis is that Sitagliptin will improve overall blood glucose, fasting blood glucose, and glycemic excursions in patients with Type I Diabetes. In addition, sitagliptin will likely suppress indices of oxidative stress in patients. The study will investigate proposed mechanisms of improved glucose concentrations, including enhanced effect of endogenous GLP-1 and suppression of glucagon.

Official Title
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Effect of Sitagliptin on Glycemic Control, Post-prandial Glucagon, and Inflammation in Type 1 Diabetics

Conditions
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Diabetes Type I

Intervention / Treatment
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* Drug: sitagliptin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female adult, aged 18 to 70 years Type 1 Diabetes Mellitus for 6 months or more, as established by medical history Current treatment with multiple injections of insulin (at least 4) or CSII (continuous subcutaneous insulin infusion or insulin pump) therapy for at least 3 months prior to screening visit; and using the same insulin during the last 1 month HbA1c ≤ 8.5% Subjects should routinely practice at least 2-4 blood glucose measurements per day BMI ≤ 35 kg/m2 Subject must be able and willing to perform self-blood glucose monitoring and accept wearing a continuous glucose monitor for 3 days at the start and 3 days at the end of the study Subjects must be willing to complete study visits per study protocol Able to speak, read, and write English Exclusion Criteria: Type 1 Diabetes Mellitus for less than 6 months Coronary Event or procedure (myocardial infarction, unstable angina, coronary artery bypass surgery, or coronary angioplasty) in the previous 4 weeks Any other life-threatening, non-cardiac disease Pregnant or intends to become pregnant during the course of the study Severe unexplained hypoglycemia that required emergency treatment over the past 3 months History of hemoglobinopathies Post-renal transplantation, currently undergoing dialysis, creatinine of >1.5mg/dl or a calculated creatinine clearance of <50 mL/min. Have extensive skin changes/diseases that inhibit wearing the sensor on normal skin Subjects who have an allergy to medication being used Current participation in another study protocol History of autonomic neuropathy or gastroparesis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin<br> | Drug: sitagliptin<br>* sitagliptin 100mg by mouth once a day for 12 weeks<br>* Other names: Januvia/Sitagliptin 100mg;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Take one by mouth daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in mean glucose concentrations | The primary endpoint of the study is to detect the change from baseline in mean glucose concentrations as measured by both HbA1c, and mean glucose over the three days of continuous glucose monitoring. | baseline and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic changes | Glycemic changes including standard deviations of the glycemic levels, fructosamine, and the duration of time spent in hyperglycemia and hypoglycemia. | baseline and 3 months | 
| Post meal hyperglycemia | Post meal hyperglycemia will be measured as area under the curve (AUC). | baseline and 3 months | 
| Changes in post prandial glucose, glucagon, insulin, c-peptide, DPP-IV, GIP and, GLP-1 concentrations following meal challenge. |  | baseline and 3 months | 
| Changes in NF kappa B in the fasting state. |  | baseline and 3 months | 
| Change in NFkappaB following meal challenge. |  | baseline and 3 Months |