Using GLP-1 therapy to improve glucose tolerance in cystic fibrosis patients

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

This study is testing if a weekly injection of a diabetes medication can help adults with cystic fibrosis improve their blood sugar levels and insulin response.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Locations: 2 sites (Aurora, Colorado and 1 other locations)
• Trial ID: NCT04731272 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of dulaglutide, a GLP-1 agonist, on improving insulin secretion and glucose tolerance in adults with cystic fibrosis-related diabetes. The study aims to determine if weekly administration of this medication can enhance early-phase insulin secretion during a mixed-meal tolerance test. Participants will include individuals diagnosed with cystic fibrosis and pancreatic insufficiency who exhibit abnormal glucose tolerance. The trial will assess the potential of this intervention to delay or prevent the progression of diabetes in these patients.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of cystic fibrosis and pancreatic insufficiency, who also exhibit abnormal glucose tolerance.

Not a fit: Patients with cystic fibrosis who do not have abnormal glucose tolerance or those with uncontrolled fasting hyperglycemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve glucose management and overall health outcomes for patients with cystic fibrosis-related diabetes.

How similar studies have performed: Other studies have shown promising results with GLP-1 agonists in improving glucose metabolism, suggesting potential success for this approach in cystic fibrosis-related diabetes.

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

Where this trial is running

Aurora, Colorado and 1 other locations

• Children's Hospital of Colorado — Aurora, Colorado, United States (RECRUITING)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Principal investigator: Michael R Rickels, MD, MS — University of Pennsylvania
• Study coordinator: Paola Alvarado, MS

Conditions: Cystic Fibrosis, Pancreatic Insufficiency, Abnormal Glucose Tolerance, Diabetes, Cystic Fibrosis Related Diabetes, Glucose Intolerance, Insulin Secretion, Glucagon-Like Peptide-1