GLP-1 Agonist Therapy in Cystic Fibrosis-Related Glucose Intolerance

This is an interventional other trial for Cystic Fibrosis focused on measuring Cystic Fibrosis Related Diabetes, Glucose Intolerance, Insulin Secretion, Glucagon-Like Peptide-1 (GLP-1) Read More

Inclusion Criteria:

• 1. Male or female, aged ≥18 years on date of consent
• 2. Confirmed diagnosis of CF, defined by positive sweat test or Cystic Fibrosis transmembrane conductance regulator (CFTR) mutation analysis according to Cystic Fibrosis Foundation (CFF) diagnostic criteria.
• 3. Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
• 4. Abnormal glucose tolerance defined by oral glucose tolerance test (OGTT) criteria for early glucose intolerance (EGI), impaired glucose tolerance (IGT), or CFRD without fasting hyperglycemia (fasting hyperglycemia is defined as fasting glucose ≥126 mg/dL)
• 5. Ability to take subcutaneous medication and be willing to adhere to the weekly administration regimen and complete study specific procedures (MMTT)
• 6. For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 6 weeks after the end of dulaglutide or observation administration; oral contraceptives, intra-uterine devices, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable

Exclusion Criteria:

• 1. BMI <19 kg/m2
• 2. Presence of first-degree atrioventricular block or other evidence for cardiac conduction system or structural heart defects
• 3. Pregnancy or lactation; a negative urine pregnancy test will be required at enrollment
• 4. Known allergic reactions to any GLP-1 agonist, and any history of severe hypersensitivity reactions (anaphylaxis or angioedema)
• 5. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)
• 6. Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to study procedures
• 7. Gastrointestinal symptom exacerbation defined by current nausea/vomiting or diarrhea
• 8. Established diagnosis of non-CF diabetes (e.g. type 1 diabetes) or CFRD with fasting hyperglycemia (fasting glucose ≥126 mg/dL [use of prandial insulin or repaglinide will be permitted])
• 9. History of clinically symptomatic pancreatitis within the last year
• 10. Prior lung, liver or other solid organ transplant
• 11. Severe CF liver disease, as defined by the presence of portal hypertension
• 12. History of fundoplication-related dumping syndrome
• 13. Hemoglobin <10 g/dL, within 90 days of study procedures or at screening
• 14. Abnormal renal function, within 90 days of study procedures or at screening; defined as creatinine >2x upper limit of normal (ULN) or potassium >5.5mEq/L on non-hemolyzed specimen
• 15. History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk to the subject