Understanding how incretin hormones affect insulin in cystic fibrosis patients

Determination of Beta-cell Responsiveness to the Incretin Hormones GLP-1 and GIP in Cystic Fibrosis

This study tests if giving incretin hormones can help improve insulin production in cystic fibrosis patients who have diabetes.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT01851694 on ClinicalTrials.gov

What this trial studies

This research focuses on cystic fibrosis related diabetes (CFRD), a condition that affects many cystic fibrosis patients. The study aims to investigate the role of incretin hormones, which are known to enhance insulin production, in improving insulin secretion from beta cells in patients with CFRD. Participants will receive either incretin hormones or a placebo, and their insulin release will be measured to determine the effectiveness of the treatment. The study will provide valuable insights into the mechanisms of CFRD and potential treatment options.

Who should consider this trial

Good fit: Ideal candidates include adults with a confirmed diagnosis of cystic fibrosis and pancreatic insufficiency who exhibit specific glucose tolerance test results.

Not a fit: Patients with established non-CF diabetes or those with fasting hyperglycemia will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for cystic fibrosis related diabetes, enhancing insulin production and overall patient health.

How similar studies have performed: While there is limited understanding of CFRD, studies on incretin hormones in other diabetes types have shown promising results, suggesting potential for success in this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
2. Age greater than or equal to 18y on date of consent
3. Pancreatic insufficiency
4. Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
5. For female subjects, negative urine pregnancy test at enrollment.

Control Subjects:

1. No history of cystic fibrosis.
2. Age ≥ 18y on date of consent.
3. Recent OGTT consistent with NGT.
4. For female subjects, negative urine pregnancy test at enrollment.

Exclusion Criteria:

1. Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
2. History of clinically symptomatic pancreatitis within last year
3. Prior lung or liver transplant
4. Severe CF liver disease, as defined by portal hypertension
5. Fundoplication-related dumping syndrome
6. Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
7. Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
8. Treatment with oral or intravenous corticosteroids within 6 weeks of study
9. Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
10. Abnormal renal function, within 90 days of Visit 1 or at Screening; defined as Creatinine greater than 2x upper limit of normal (ULN) or potassium greater than 5.5mEq/L on non-hemolyzed specimen
11. Inability to perform study specific procedures (MMTT, GPA)
12. Subjects, who in study team opinion, may be non-compliant with study procedures.

Control Subjects who will be exposed to GIP only:

1. History of clinically symptomatic pancreatitis.
2. History of liver disease.
3. 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.
4. Hemoglobin \<10g/dL, within 90 days of GPA test or at Screening.
5. Abnormal renal function, within 90 days of GPA test or at Screening; defined as creatinine \> 2x upper limit of normal (ULN) or potassium \> 5.5mEq/L on non-hemolyzed specimen.
6. Inability to perform study specific procedures (MMTT, GPA).
7. subjects, who in study team opinion, may be non-compliant with study procedures.
8. elevation of serum amylase or lipase \> 1.5x ULN within 90 days of GPA test.

Where this trial is running

Philadelphia, Pennsylvania

• Children's Hospital of Philadelphia and University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

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

Conditions Cystic Fibrosis; Pancreatic Insufficiency; Diabetes; Pancreatic insufficiency; Cystic Fibrosis with Normal Glucose Tolerance; Non-Cystic Fibrosis control group