Treatment of Dysglycemia Using Sitagliptin in Adolescents With Cystic Fibrosis

Study Overview
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Brief Summary
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This pilot study will be conducted in adolescents with cystic fibrosis (CF) without diabetes but with abnormal glucose tolerance, and will assess the effects of sitagliptin on glucose regulation. An oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT), will be performed at baseline and again  4 weeks after treatment with study drug. We will also look at blood sugars throughout the day using a continuous glucose monitor (CGM) before each time the MMTT/OGTT are performed. Several hormones that may affect the way the body regulates blood sugars will be measured in blood when the OGTT and MMTT are done. We will assess the effect this medicine has on blood sugars (using CGM) and the effect the medicine has on the hormones measured during the OGTT and MMTT.

Official Title
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Treatment of Dysglycemia Using Sitagliptin in Adolescents With Cystic Fibrosis.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Sitagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CF between 13 and <21 yrs old Known impaired or indeterminate glucose tolerance (based on a prior OGTT) No history of CFRD Exclusion Criteria: Insulin use in the last two months Acute pulmonary exacerbation / oral corticosteroid use in the last 6 weeks History of pancreatitis in the last 12 months Skin rashes or conditions that may affect CGM placement and wear Pregnancy or intent on becoming pregnant Patients on growth hormone therapy Renal insufficiency with creatinine clearance <50 ml/min (based on Schwartz formula)

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 20 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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin<br>Treatment with sitagliptin | Drug: Sitagliptin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to sitagliptin | Baseline and stimulated C-peptide levels (using mixed meal tolerance test) before and after treatment with sitagliptin. | Change from baseline to  4 weeks of study drug | 
| Response to sitagliptin | Change in glycemic variability using continuous glucose monitoring data before and after treatment with dipeptidyl peptidase-4 inhibitor. | Change from baseline to  4 weeks of study drug | 
| Response to sitagliptin | Change in incretins concentrations (glucagon like peptide 1; glucose-dependent insulinotropic polypeptide) in response to study drug. | Change from baseline to  4 weeks of study drug | 
| Response to sitagliptin | Change in incretin (glucagon like peptide 1; glucose-dependent insulinotropic polypeptide) concentrations in response to study drug. | Change from baseline to  4 weeks of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell function | Beta-cell function will be measured using mixed meal tolerance tests (MMTT) and oral glucose tolerance tests (OGTT), assessing maximum concentration and area under the curve (AUC) of glucose, insulin and c-peptide for both OGTT and MMTT. | Change from baseline to  4 weeks of study drug | 
| Continuous glucose monitoring (CGM) | Baseline and post-treatment changes in glycemic variability using CGM, including mean amplitude of glycemic excursion (MAGE), peak post-prandial blood sugars, and glucose area under the curve. | change from baseline to  4 weeks of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cystic fibrosis, CF, CFRD, sitagliptin, incretins, GLP1, GIP, beta cell function, adolescents