Effect of Chronic Incretin-based Therapy in Cystic Fibrosis
In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 and Type 2 diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin. 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 Type 1 and Type 2 diabetes, it is very different; therefore, treatment and care of CFRD is not the same.
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. The primary objective is to determine effectiveness of chronic incretin-based therapy vs. placebo on insulin secretion in CF patients with indeterminate glucose tolerance, impaired glucose tolerance, or CFRD.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
|Official Title:||A Randomized, Double-blind, Placebo Controlled Study of the Effectiveness of Chronic Incretin-based Therapy on Insulin Secretion in Cystic Fibrosis|
- Change in second-phase insulin response derived from the glucose-potentiated arginine test as a measure of β-cell sensitivity to glucose at baseline and at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]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 the 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 340 mg/dl and the arginine injection will be repeated. Comparison of responses at baseline and after 6 months of incretin-based therapy (Sitagliptin) or placebo will be performed using statistical methods.
|Study Start Date:||June 2013|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
The dose of sitagliptin (Januvia®) will be 100 mg tablet orally each morning for 6 months.
The GPA test as described in the primary outcome section will be performed at baseline and after 6 months of therapy in the Sitagliptin and placebo arms. Furthermore, evaluation of endogenous GLP-1 levels will be assessed by a mixed meal tolerance test compared at baseline and 6 months.
Other Name: Januvia
Placebo Comparator: Placebo
Placebo tablet will be orally each morning for 6 months.
Insufficient incretin action has been associated with T2D. To study the possible link between insufficient incretin action and impaired insulin secretion in CFRD as in T2D, the present study will determine whether early intervention with incretin-based therapy using the DPP-4 inhibitor sitagliptin (Januvia®) to raise endogenous levels of the incretin hormones--i.e.--glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic polypeptide (GIP) for a 6-month period will improve insulin secretion in CF patients with indeterminate glucose tolerance, impaired glucose tolerance or early CFRD.
|Contact: Christina Kubrak, RRTfirstname.lastname@example.org|
|Contact: Nora Rosenfeldemail@example.com|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia and University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19194|
|Contact: Christina Kubrak, RRT 267-426-5135|
|Principal Investigator: Michael M Rickels, MD, MS|
|Principal Investigator: Andrea Kelly, M.D., M.S|
|Principal Investigator:||Michael M Rickels, MD||University of Pennsylvania|