Beta-cell Response to Incretin Hormones in Cystic Fibrosis

ConditionsCystic Fibrosis Pancreatic Insufficiency

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorUniversity of Pennsylvania

About this trial

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

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

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

Treatment groups

45 Participants

are divided into 2 treatment groups

Group A: GLP-1 Incretin HormoneExperimental treatment 1 intervention

Group B: GIP Incretin HormoneExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

5 hours

Secondary outcomes

Change in insulin secretion among CF groups

The change in second phase insulin secretion induced by incretins will be compared among the different subgroups of patients with CF (Ind-GT, IGT, and early CFRD) groups using nonparametric comparison of changes in slope, estimated using Mann-Whitney methods.

Time frame

5 hours

Sponsors and contacts

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University of Pennsylvania

Lead sponsor

Children's Hospital of Philadelphia

Collaborator

Source ClinicalTrials.gov

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