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

NCT04731272 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 848357
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Cystic Fibrosis; Pancreatic Insufficiency; Abnormal Glucose Tolerance; Diabetes

Keywords

Cystic Fibrosis Related Diabetes; Glucose Intolerance; Insulin Secretion; Glucagon-Like Peptide-1 (GLP-1)

Outcome Measures

Primary Outcomes (1)

• Early-phase insulin secretion

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

  18 weeks

Secondary Outcomes (2)

• Early-phase insulin secretion adjusted for glucose excursion

  18 weeks

• Glucose tolerance

  18 weeks

Study Arms (2)

Dulaglutide

EXPERIMENTAL

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

Observation

NO INTERVENTION

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.

Interventions

Dulaglutide 0.75Mg/0.5Ml Inj Pen DRUG

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

Dulaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Male or female, aged ≥18 years on date of consent
• \. 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.
• \. Pancreatic insufficiency defined by clinical requirement for pancreatic enzyme replacement.
• \. Abnormal glucose tolerance defined by OGTT criteria for EGI, IGT, or CFRD, or diagnosed CFRD.
• 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)
• 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.
• \. Ability to take subcutaneous medication and be willing to adhere to the weekly administration regimen and complete study specific procedures (MMTT)
• \. 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

You may not qualify if:

• \. BMI \<19 kg/m2
• \. Presence of first-degree atrioventricular block or other evidence for cardiac conduction system or structural heart defects
• \. Pregnancy or lactation; a negative urine pregnancy test will be required at enrollment
• \. Known allergic reactions to any GLP-1 agonist, and any history of severe hypersensitivity reactions (anaphylaxis or angioedema)
• \. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2)
• \. Pulmonary exacerbation requiring IV antibiotics or systemic glucocorticoids within 4 weeks prior to study procedures
• \. Gastrointestinal symptom exacerbation defined by current nausea/vomiting or diarrhea
• \. Established diagnosis of non-CF diabetes (e.g. type 1 diabetes) or CFRD with fasting hyperglycemia (fasting glucose ≥126 mg/dL \[use of prandial insulin or repaglinide will be permitted\])
• \. History of clinically symptomatic pancreatitis within the last year
• \. Prior lung, liver or other solid organ transplant
• \. Severe CF liver disease, as defined by the presence of portal hypertension
• \. History of fundoplication-related dumping syndrome
• \. Hemoglobin \<10 g/dL, within 90 days of study procedures or at screening
• \. 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
• \. 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Children's Hospital of Philadelphia: collaborator
• Children's Hospital Colorado: collaborator

Study Sites (2)

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Diabetes Mellitus; Glucose Intolerance

Interventions

dulaglutide

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Study Officials

• Michael R Rickels, MD, MS

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Andrea Kelly, MD, MSCE

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Alvarado, MS

CONTACT

215-746-2081; Paola.Alvarado@pennmedicine.upenn.edu

Cornelia Dalton-Bakes

CONTACT

215-746-2085; corneliv@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: January 29, 2021
• Study Start: July 16, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 27, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Upon completion of enrollment.
• Access Criteria: Consent will be uploaded to CT.gov

Locations

US (2)