Effect of Chronic Incretin-based Therapy in Cystic Fibrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of Pennsylvania
Sponsor:
Collaborator:
Children's Hospital of Philadelphia
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01879228
First received: June 12, 2013
Last updated: September 10, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention
Cystic Fibrosis
Pancreatic Insufficiency
Drug: Sitagliptin

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 36
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)
Arms Assigned Interventions
Experimental: Sitagliptin
The dose of sitagliptin (Januvia®) will be 100 mg tablet orally each morning for 6 months.
Drug: Sitagliptin
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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1) Confirmed diagnosis of CF, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria, 2) age ≥ 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.

Exclusion Criteria:

  • 1) Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia, (fasting glucose > 126 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 enrollment, 8) treatment with oral or intravenous corticosteroids within 6 weeks of enrollment, 9) hemoglobin <10g/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 clearance < 50 mL/min (based on the Cockcroft-Gault formula) or potassium > 5.5mEq/L on non-hemolyzed specimen, 11) a history of anaphylaxis, angioedema or Stevens-Johnson syndrome, 12) Inability to perform study specific procedures (MMTT, GPA), 13) Subjects, who in study team opinion, may be non-compliant with study procedures.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01879228

Contacts
Contact: Christina Kubrak, RRT 267-426-5135 kubrak@email.chop.edu
Contact: Nora Rosenfeld 215-746-2081 nora.rosenfeld@uphs.upenn.edu

Locations
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         
Sponsors and Collaborators
University of Pennsylvania
Children's Hospital of Philadelphia
Investigators
Principal Investigator: Michael M Rickels, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01879228     History of Changes
Other Study ID Numbers: 818014
Study First Received: June 12, 2013
Last Updated: September 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Cystic Fibrosis
Diabetes
Pancreatic Insufficiency

Additional relevant MeSH terms:
Fibrosis
Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Sitagliptin
Incretins
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014