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

Launched by UNIVERSITY OF PENNSYLVANIA · Jan 26, 2021

Keywords

ClinConnect Summary

This clinical trial is studying a medication called dulaglutide to see if it can help improve blood sugar levels in adults with cystic fibrosis who also have issues with glucose tolerance or diabetes. Cystic fibrosis-related diabetes (CFRD) is a common problem for people with cystic fibrosis, which can lead to serious health issues. The researchers believe that giving dulaglutide once a week might help the body release insulin more effectively, especially after meals, and improve overall glucose control.

To participate in this trial, individuals must be at least 18 years old, have a confirmed diagnosis of cystic fibrosis and pancreatic insufficiency, and show signs of abnormal glucose tolerance. Participants should be able to take the medication by injection once a week and complete specific study tests. However, there are certain conditions that would exclude someone from joining, such as a very low body mass index (BMI) or a history of severe heart problems. If eligible, participants will receive the study medication and will be closely monitored throughout the trial, helping to advance our understanding of how to better manage diabetes in cystic fibrosis patients.

Gender

ALL

Eligibility criteria

• 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 OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
• • 1. There will be no restriction on enrollment of individuals with CFRD but without fasting hyperglycemia (fasting hyperglycemia is defined as fasting glucose ≥126 mg/dL)
• • 2. Individuals with CFRD and fasting hyperglycemia (defined as above or by the use of basal insulin therapy) must also have a HbA1c ≤8% and a random (non-fasting) C-peptide ≥1.2 ng/mL17; enrollment of this subgroup will be limited to n =10.
• • 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