Beta-cell Response to Incretin Hormones in Cystic Fibrosis

NCT01851694 | Recruiting DMC

• 1 other identifier: 817585
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Insulin is a hormone which is made by cells in the pancreas and helps carry glucose (sugar) from the food we eat to the cells of the body for energy. While cystic fibrosis related diabetes (CFRD) has many features similar to both T1D and T2D, patients with CF may not have the same symptoms as either T1D or T2D patients. Currently, there is little understanding of CFRD and the best options for treatment remain unclear. The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. In particular, we plan to study the effects of incretin hormones that can enhance insulin production in CF patients. Enrollment is complete for the protocol as initially written. In order to further study the role of the incretin hormone on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function , we have received approval to extend our investigation to include the following study groups:

• Cystic Fibrosis participants with normal glucose tolerance
• Non-Cystic Fibrosis controls

Conditions

Cystic Fibrosis; Pancreatic Insufficiency

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Second-phase insulin response during GPA test

  The key endpoint of interest will be the change in second phase insulin response derived from the Glucose-Potentiated Arginine (GPA) test. The GPA test will measure insulin (and other glucose controlling hormones) which will be a measure of pancreatic endocrine function in response to injection of arginine. Arginine is a naturally occurring amino acid (substance) in the body. It will be given in the veins to make the pancreas secrete insulin. After the first injection of arginine, a glucose infusion will be started in order to raise the level of sugar in the blood to 230 mg/dl. Once the level is achieved, arginine will be injected again and blood samples are measured. After a 2 hour break, the glucose infusion will be started to achieve a blood sugar of 340mg/dl and arginine injection will be repeated. Comparison of responses with incretin vs. placebo will be performed using statistical methods, specifically, paired t-test or Wilcoxon matched pair test.

  5 hours

Secondary Outcomes (1)

• Change in insulin secretion among CF groups

  5 hours

Study Arms (2)

GLP-1 Incretin Hormone

EXPERIMENTAL

The incretin, Glucagon-Like-peptide-1 (GLP-1) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins. (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion.

Drug: GLP-1

GIP Incretin Hormone

EXPERIMENTAL

The incretin, Glucose-dependent Insulinotropic Polypeptide (GIP) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion.

Drug: GIP

Interventions

GLP-1 DRUG

Each subject in this arm will receive GLP-1 infusion and a placebo infusion during a GPA test.

GLP-1 Incretin Hormone

GIP DRUG

Each subject in this arm will receive GIP infusion and placebo during a GPA test.

Also known as: Glucose-dependent insulinotrophic polypeptide

GIP Incretin Hormone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
• Age greater than or equal to 18y on date of consent
• Pancreatic insufficiency
• Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
• For female subjects, negative urine pregnancy test at enrollment.
• Control Subjects:
• No history of cystic fibrosis.
• Age ≥ 18y on date of consent.
• Recent OGTT consistent with NGT.
• For female subjects, negative urine pregnancy test at enrollment.

You may not qualify if:

• Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
• History of clinically symptomatic pancreatitis within last year
• Prior lung or liver transplant
• Severe CF liver disease, as defined by portal hypertension
• Fundoplication-related dumping syndrome
• Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
• Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
• Treatment with oral or intravenous corticosteroids within 6 weeks of study
• Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
• 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
• Inability to perform study specific procedures (MMTT, GPA)
• Subjects, who in study team opinion, may be non-compliant with study procedures.
• Control Subjects who will be exposed to GIP only:
• History of clinically symptomatic pancreatitis.
• History of liver disease.

Sponsors & Collaborators

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

Study Sites (1)

Children's Hospital of Philadelphia and University of Pennsylvania

Philadelphia, Pennsylvania, 19060, United States

RECRUITING

Related Publications (1)

• Nyirjesy SC, Peleckis AJ, Eiel JN, Gallagher K, Doliba A, Tami A, Flatt AJ, De Leon DD, Hadjiliadis D, Sheikh S, Stefanovski D, Gallop R, D'Alessio DA, Rubenstein RC, Kelly A, Rickels MR. Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis. Diabetes. 2022 Oct 1;71(10):2153-2165. doi: 10.2337/db22-0399.

  PMID: 35796669 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Diabetes Mellitus

Interventions

Glucagon-Like Peptide 1

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Michael R. Rickels, MD, MS

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paola Alvarado

CONTACT

215-746-2081; paola.alvarado@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 8, 2013
• First Posted: May 10, 2013
• Study Start: May 1, 2013
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon completion of enrollment, once our data has been analyzed. Informed Consent has already been shared.
• Access Criteria: Will upload on clinical trials.gov and attach to results section. Informed Consent has already been shared on ct.gov.

Locations

US (1)