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

NCT ID: NCT04731272

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-16
• Study Completion Date: 2027-06-30

Brief Summary

Diabetes is a major co-morbidity in pancreatic insufficient cystic fibrosis (PI-CF) and associated with worse outcomes. While reduced β-cell mass contributes to the insulin secretory defects that characterizes cystic fibrosis-related diabetes (CFRD), other modifiable determinants appear operative in the emergence and progression of abnormal glucose tolerance towards diabetes. Identifying interventions to preserve β-cell function are crucial for delaying and potentially preventing CFRD development. In this study, we hypothesize that weekly administration of the long-acting glucagon-like peptide-1 (GLP-1) agonist dulaglutide will improve defective early-phase insulin secretion and improve glucose tolerance during a mixed-meal tolerance test.

Detailed Description

Diabetes is a major co-morbidity in pancreatic insufficient cystic fibrosis (PI-CF) and associated with worse outcomes. While reduced β-cell mass contributes to the insulin secretory defects that characterizes cystic fibrosis-related diabetes (CFRD), other modifiable determinants appear operative in the emergence and progression of abnormal glucose tolerance towards diabetes. Identifying interventions to preserve β-cell function are crucial for delaying and potentially preventing CFRD development. In this study, we hypothesize that weekly administration of the long-acting glucagon-like peptide-1 (GLP-1) agonist dulaglutide will improve defective early-phase insulin secretion and improve glucose tolerance during a mixed-meal tolerance test.

Conditions

Cystic Fibrosis; Pancreatic Insufficiency; Abnormal Glucose Tolerance; Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Dulaglutide

The Mixed Meal Tolerance Test as described in the primary outcome section will be performed at baseline and after 6 weeks of dulaglutide therapy in the intervention period.

Group Type: EXPERIMENTAL

Dulaglutide 0.75Mg/0.5Ml Inj Pen

Intervention Type: DRUG

Randomized, open-label, cross-over study of 6 weeks exposure to dulaglutide 0.75 mg subcutaneous weekly or observation.

Observation

The Mixed Meal Tolerance Test as described in the primary outcome section will be performed at baseline and after 6 weeks of no intervention in the observation period.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dulaglutide 0.75Mg/0.5Ml Inj Pen

Randomized, open-label, cross-over study of 6 weeks exposure to dulaglutide 0.75 mg subcutaneous weekly or observation.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: collaborator

Children's Hospital Colorado

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Michael R. Rickels, MD, MS

Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael R Rickels, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Andrea Kelly, MD, MSCE

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Colorado

Aurora, Colorado, United States

Site Status: RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Paola Alvarado, MS

Role: CONTACT

Paola.Alvarado@pennmedicine.upenn.edu

215-746-2081

Cornelia Dalton-Bakes

Role: CONTACT

corneliv@pennmedicine.upenn.edu

215-746-2085

Facility Contacts

Hannah Wessel

Role: primary

Hannah.Wessel@childrenscolorado.org

720-777-1880 ext. 71880

Christine Chan, MD

Role: backup

Christinel.Chan@childrenscolorado.org

720-777-0990 ext. 70990

Paola Alvarado, MS

Role: primary

Paola.Alvarado@pennmedicine.upenn.edu

215-746-2081

Cornelia Dalton-Bakes

Role: backup

corneliv@pennmedicine.upenn.edu

215-746-2085

Other Identifiers

848357

Identifier Type: -

Identifier Source: org_study_id