Cystic Fibrosis Related Diabetes

Study Overview
=================
Brief Summary
-----------------
Cystic Fibrosis (CF) is a chronic disease characterized by recurrent pulmonary infections and exocrine pancreatic insufficiency. The vast majority of patients with CF will develop pancreatic endocrine insufficiency over time manifested as altered glucose metabolism. The presence of overt diabetes in patients with CF is associated with adverse clinical outcomes. The underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter of investigation. In addition to localized tissue damage developing similar to that of the exocrine pancreas, additional mechanisms may be involved. The investigators have recently shown that insulin secretion in patients with CF is significantly altered prior to the development of diabetes. This phenomenon is associated with reduced secretion of gut derived incretins (specifically GIP). The blunting of incretin induced insulin secretion (whether due to a deranged interaction of gastrointestinal contents with enterocytes resulting in reduced secretion or due to rapid clearance of such peptides) may be a major underlying driver of altered glucose metabolism in such patients.

Official Title
-----------------
DPP-IV Inhibition in Patients With Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: Saxagliptin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years No diabetes based on screening OGTT No C/I for use of the medications Normal kidney function Willing and able to participate Exclusion Criteria: Use of anti-hyperglycemic medications Acute illness or infection at enrollment

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saxagliptin administration<br>Saxagliptin Administration- The participants in this study will undergo an OGTT (Oral Glucose Tolerance Test) at recruitment and then will start treatment with the DPP IV inhibitor- Saxagliptin. After 6 weeks of treatment the participants will return to perform a second OGTT. | Drug: Saxagliptin<br>* The participants in this study will undergo an OGTT at recruitment and then will start treatment with the DPP IV inhibitor- Saxagliptin at a dose between 2.5- 5mg a day. After 6 weeks of treatment the participants will return to perform a second OGTT.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glucose tolerance after treatment with Saxagliptin | Bloods taken during the OGTT will be analyzed for Glucose, Insulin, C-peptide and glucagon levels. Gut hormone levels and incretins will also be valued. | The outcome will be measured at 2 timepoints. at baseline and 6 weeks after Saxagliptin treatment |