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

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04731272
• Collaborator: Children's Hospital of Philadelphia (Other)
• Enrollment: 30
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 74.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis; Pancreatic Insufficiency; Abnormal Glucose Tolerance; Diabetes	Drug: Dulaglutide 0.75Mg/0.5Ml Inj Pen	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Effect of GLP-1 Agonist Therapy on Insulin Secretion in Adults With Pancreatic Insufficient Cystic Fibrosis and Abnormal Glucose Tolerance: a Randomized, Open-label, Cross-over Trial
• Actual Study Start Date: Apr 20, 2021
• Anticipated Primary Completion Date: Jun 30, 2026
• Anticipated Study Completion Date: Jun 30, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: 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.
No Intervention: 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.

Outcome Measures

Primary Outcome Measures

1. Early-phase insulin secretion [18 weeks]

   The primary outcome measure is the insulin secretory rate during the first 30-min during a mixed meal tolerance test (ISR-AUC30).

Secondary Outcome Measures

1. Early-phase insulin secretion adjusted for glucose excursion [18 weeks]

   This secondary outcome measure is insulin secretory rate/glucose area under cure during the first 30-min during a mixed meal tolerance test (ISR-AUC30/ Glc-AUC30)

2. Glucose tolerance [18 weeks]

   This secondary outcome measure is mixed meal tolerance test-related glucose area under the curve over 180 min (Glc-AUC180).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Male or female, aged ≥18 years on date of consent
• 1. 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.
• 1. Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
• 1. 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)
• 1. Ability to take subcutaneous medication and be willing to adhere to the weekly administration regimen and complete study specific procedures (MMTT)
• 1. 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
• 1. Presence of first-degree atrioventricular block or other evidence for cardiac conduction system or structural heart defects
• 1. Pregnancy or lactation; a negative urine pregnancy test will be required at enrollment
• 1. Known allergic reactions to any GLP-1 agonist, and any history of severe hypersensitivity reactions (anaphylaxis or angioedema)
• 1. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)
• 1. Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to study procedures
• 1. Gastrointestinal symptom exacerbation defined by current nausea/vomiting or diarrhea
• 1. 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])
• 1. History of clinically symptomatic pancreatitis within the last year
• 1. Prior lung, liver or other solid organ transplant
• 1. Severe CF liver disease, as defined by the presence of portal hypertension
• 1. History of fundoplication-related dumping syndrome
• 1. Hemoglobin <10 g/dL, within 90 days of study procedures or at screening
• 1. 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
• 1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Children's Hospital of Philadelphia

Investigators

• Principal Investigator: Michael R Rickels, MD, MS, University of Pennsylvania
• Principal Investigator: Andrea Kelly, MD, MSCE, Children's Hospital of Philadelphia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael R. Rickels, MD, MS, Professor of Medicine, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04731272
• Other Study ID Numbers: 848357
• First Posted: Jan 29, 2021
• Last Update Posted: Jan 11, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Michael R. Rickels, MD, MS, Professor of Medicine, University of Pennsylvania: Cystic Fibrosis Related Diabetes; Glucose Intolerance; Insulin Secretion; Glucagon-Like Peptide-1 (GLP-1)
• Additional relevant MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Glucose Intolerance; Fibrosis; Dulaglutide

Study Results

No Results Posted as of Jan 11, 2022