RECRUITING

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

Conditions

Cystic Fibrosis Pancreatic Insufficiency Abnormal Glucose Tolerance Diabetes Cystic Fibrosis Related Diabetes Glucose Intolerance Insulin Secretion Glucagon-Like Peptide-1 (GLP-1)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

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

Quick Facts

Study Start:2021-04-20

Study Completion:2027-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04731272

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Paola Alvarado, MS

CONTACT

215-746-2081

Paola.Alvarado@pennmedicine.upenn.edu

Cornelia Dalton-Bakes

CONTACT

215-746-2085

corneliv@pennmedicine.upenn.edu

Principal Investigator

Michael R Rickels, MD, MS

PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Andrea Kelly, MD, MSCE

PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Study Locations (Sites)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: University of Pennsylvania

Michael R Rickels, MD, MS, PRINCIPAL_INVESTIGATOR, University of Pennsylvania
Andrea Kelly, MD, MSCE, PRINCIPAL_INVESTIGATOR, Children's Hospital of Philadelphia

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-20

Study Completion Date2027-06-30

Study Record Updates

Study Start Date2021-04-20

Study Completion Date2027-06-30

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Cystic Fibrosis
Pancreatic Insufficiency
Abnormal Glucose Tolerance
Diabetes