Prevention of Cystic Fibrosis Diabetes

This study is currently recruiting participants.
Verified March 2014 by Emory University
Information provided by (Responsible Party):
Arlene Stecenko, Emory University Identifier:
First received: August 27, 2009
Last updated: March 13, 2014
Last verified: March 2014

Acute systemic hyperglycemia causes oxidative stress and a pro-inflammatory response. The pro-inflammatory cytokines induced by hyperglycemia are toxic to islet insulin producing cells, and thus worsen glucose intolerance. Patients with cystic fibrosis (CF) have a high prevalence of CF related diabetes (CFRD) and up to 40% of CF adults develop CFRD. During the prediabetic phase in CF, there is progression from normal glucose homeostasis to high risk prediabetes characterized by episodes of acute hyperglycemia after meals and during respiratory exacerbations. The mild hyperglycemia seen in CF patients with high risk prediabetes following a meal would be expected to induce a degree of systemic inflammation and oxidative stress. These repetitive episodes, if left unchecked, could lead to progression of glucose impairment, worsening severity of oxidative stress and inflammation, and ultimately the development of CFRD, all via hyperglycemia-induced toxicity to beta cells. Furthermore, this process may be accelerated in CF because lung disease and resultant respiratory exacerbations are associated with oxidative stress and inflammation and this will further contribute to beta cell damage.

Sitagliptin is a recently approved agent for type 2 diabetes and markedly enhances insulin secretion in the presence of hyperglycemia and has been shown to be effective in preventing postprandial hyperglycemia. The hypothesis to be tested in this project is that sitagliptin will prevent the development of CFRD in CF subjects with high risk prediabetes by blocking postprandial hyperglycemia. The investigators propose a randomized, double-blind, placebo-controlled, multicenter, 27-month longitudinal study in 186 CF subjects with high risk prediabetes to test this hypothesis. Specifically, the investigators aim to show that chronic treatment with sitagliptin: prevents the conversion to diabetes; results in preservation of beta cell function; reduces systemic measures of oxidative stress and inflammation; and slows the rate of progression of lung disease.

Funding Source - FDA Office of Orphan Products Development

Condition Intervention Phase
Cystic Fibrosis
Drug: Sitagliptin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Determine Whether Chronic Treatment of Cystic Fibrosis Subjects With Impaired Glucose Tolerance Using Sitagliptin (Januvia) Prevents the Development of Diabetes

Resource links provided by NLM:

Further study details as provided by Emory University:

Primary Outcome Measures:
  • Conversion to cystic fibrosis related diabetes [ Time Frame: every two weeks for 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Preservation of beta cell function [ Time Frame: every 6 months for 2 years ] [ Designated as safety issue: No ]
  • Reduction in airway redox imbalance, oxidative stress, and inflammation [ Time Frame: every 6 months for 2 years ] [ Designated as safety issue: No ]
    Only in a subset of subjects

  • Reduction in systemic redox imbalance, oxidative stress, and inflammation [ Time Frame: every 6 months for 2 years ] [ Designated as safety issue: No ]
  • Slow the rate of progression of lung disease [ Time Frame: every 3 months for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 186
Study Start Date: May 2010
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin

CF patients receiving Sitagliptin.

Intervention: Dose is 100 mg taken orally once a day in the morning with breakfast. Duration is two years or until converted to CF diabetes, whichever comes sooner.

Drug: Sitagliptin
100 mg of sitagliptin is taken orally each morning with breakfast. Duration is 24 months or conversion to CF diabetes, whichever comes first.
Other Name: Januvia
Placebo Comparator: Sugar pill

CF patients receiving placebo.

Intervention: Placebo is taken orally once a day in the morning with breakfast. Duration is two years or until converted to CF diabetes, whichever comes sooner.

Drug: Sitagliptin
100 mg of sitagliptin is taken orally each morning with breakfast. Duration is 24 months or conversion to CF diabetes, whichever comes first.
Other Name: Januvia

  Show Detailed Description


Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Aged 13 years of age or older at the time of enrollment
  • Diagnosis of cystic fibrosis (CF) confirmed by pilocarpine iontophoresis sweat chloride measurements and/or genotyping
  • Clinically stable with no lower respiratory tract exacerbation requiring intravenous antibiotics in the three weeks prior to enrollment
  • On a stable clinical treatment regimen for at least three weeks prior to enrollment
  • Male or female. If female, is not lactating and has a negative pregnancy test at screening. If female of child bearing potential, willing to practice effective birth control (i.e. a method known to decrease the risk of pregnancy to less than 1%)
  • Able to understand and provide informed consent
  • Willing and able to comply with the study schedule and testing
  • High risk prediabetes as defined by high-risk impaired fasting glucose levels of 110-125 mg/dl and/or a 2-hour plasma glucose level of 140 to 199 mg/dl found on an Oral Glucose Tolerance Test performed at screening 8 weeks or less before enrollment
  • Available by telephone
  • Has literacy and language skills required to fill out study material

Exclusion Criteria:

  • Diagnosed with CF related diabetes
  • Chronic heart failure with NYHA class III/IV, ejection fraction less than 25%, or receiving digoxin
  • Liver disease as defined by ALT or AST three times above the upper limit of normal.
  • Serum creatinine greater than 1.3 mg/dl for males and greater than 1.1 mg/dl for females or receiving chronic dialysis
  • Taking chronic oral or intravenous glucocorticosteroids during the past month
  • On insulin therapy during the past month
  • CF lung disease severe enough to require daytime chronic oxygen therapy via nasal cannula during the past month
  • Unable to perform pulmonary function testing
  • History of any illness or condition that, in the opinion of the sponsor might confound the results of the study or pose an additional risk in administering study drug to the subject
  • Post lung or liver transplant
  • Listed and awaiting organ transplant
  • Current drug or alcohol dependency
  • Participating in another clinical drug trial or past participant within 30 days of enrollment
  • Pancreatic sufficient
  • History of acute pancreatitis as documented by characteristic clinical manifestations and elevation of serum amylase and lipase within the last 2 years.
  • Using overnight enteral tube feedings in the previous six weeks.
  Contacts and Locations
Please refer to this study by its identifier: NCT00967798

Contact: Arlene A Stecenko, MD 404 712 2657

United States, Georgia
Emory University and Children's Healthcare of Atlanta at Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Arlene A Stecenko, MD    404-712-8283   
Principal Investigator: Arlene A Stecenko, MD         
Children's Healthcare of Atlanta at Scottish Rite Recruiting
Atlanta, Georgia, United States, 30342
Contact: Kevin Kirchner, MD    404-252-7339   
Principal Investigator: Kevin Kirchner, MD         
United States, Ohio
Nationwide Children's Hospital Completed
Columbus, Ohio, United States, 43205
United States, Tennessee
Vanderbilt University Medical Center Not yet recruiting
Nashville, Tennessee, United States, 37232
Contact: Howard B Baum, MD, PhD    615-343-8332   
Principal Investigator: Howard B Baum, MD         
Canada, Quebec
Institut de Recherches Cliniques de Montreal Not yet recruiting
Montreal, Quebec, Canada, H2W 1R7
Principal Investigator: Remi Rabasa-Lhoret, MD         
Sponsors and Collaborators
Emory University
Principal Investigator: Arlene A Stecenko, MD Emory University
  More Information

No publications provided

Responsible Party: Arlene Stecenko, Associate Professor, Emory University Identifier: NCT00967798     History of Changes
Other Study ID Numbers: IRB00012724, 1RO1FD003527-01
Study First Received: August 27, 2009
Last Updated: March 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Emory University:
cystic fibrosis
oxidative stress
redox balance
lung disease

Additional relevant MeSH terms:
Cystic Fibrosis
Glucose Intolerance
Prediabetic State
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Glucose Metabolism Disorders
Metabolic Diseases
Diabetes Mellitus
Endocrine System Diseases
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs processed this record on April 17, 2014