Pilot and Feasibility Study for the Treatment of Pre-diabetes in Patients With Cystic Fibrosis

The purpose of this study is to provide the necessary data and experience to design a larger, full scale clinical trial to determine if a certain medicine (repaglinide), which increases the amount of insulin secreted by the pancreas, can improve the nutritional status and pulmonary function of adolescents and young adults with cystic fibrosis and prediabetes by improving blood glucose control. The investigators are also trying to determine the relationship between systemic inflammatory factors and glucose impairment.

Study Overview

• Status: Completed
• Conditions: Pancreatic Insufficiency; Cystic Fibrosis Related Diabetes
• Intervention / Treatment: Drug: placebo; Drug: repaglinide

Detailed Description

As people with Cystic Fibrosis (CF) are living well into adulthood new complications are arising. CF-Related Diabetes (CFRD) has emerged as a major complication. Years prior to the diagnosis of CFRD, patients have decreasing insulin secretion, glucose intolerance, deteriorating pulmonary function, and nutritional impairment. There are no current standard recommendations for the treatment of CF patients with prediabetes, and there is little evidence that treatment of this prediabetic state in CF patients will prevent the deterioration of the lung function, nutritional status and potentially slow the progression to manifest CFRD.

To determine the feasibility of testing this hypothesis, we will perform a pilot, double-blinded, randomized controlled trial in 20 CF pancreatic insufficient patients ages of 12 to 24 years old with impaired glucose tolerance test (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) and assign them to either placebo or Repaglinide 0.5 mg PO 3 - 4 times a day before meals for two years. Patients will monitor their blood glucose daily and will be followed every 3 months for 2 years to determine changes in nutritional status by BMI and DEXA, lung function tests, frequency of hospitalizations, antibiotic courses, and degree of glucose tolerance, insulin secretion and insulin sensitivity.

In addition, based on the evidence of increased inflammation in type 2 diabetes, correlation of systemic inflammatory response at different degrees of glucose tolerance and after treatment, will be assessed in these subjects, as well as in another 20 CF pancreatic insufficient matched patients with normal glucose tolerance who will be studied once without intervention

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or females 12 -24 years old
• Diagnosis of Cystic Fibrosis by sweat test with exocrine pancreatic insufficiency
• Must have a glucose pattern by Oral Glucose Tolerance Test with fasting blood glucose <126 mg/dl and 2 hour: 140 - 199 mg/dl or >200 mg/dl.
• Weight must be stable within 5% for 3 months prior to initiation visit
• Must be able to reproducibly perform spirometry based on American Thoracic Society guidelines

Exclusion Criteria:

• Patients receiving growth hormone therapy or taking insulin
• Patients with evidence of liver dysfunction
• Patients who are status-post lung or liver transplantation
• Patients who have received systemic steroids for more than 28 days during the 6 months prior to the study
• Patients with active ABPA on steroids
• Patients taking medications that affect glucose metabolism or contraindicated with repaglinide

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1 Placebo; 1 pill before each meal 3-4 times a day for 2 years. All subjects had abnormal glucose tolerance. Subjects were randomized to placebo or drug.	Drug: placebo; CF pancreatic insufficient patients with impaired glucose tolerance (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) by OGTT will be treated with placebo by taking 1 pill before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years.
Experimental: 2. repaglinide; repaglinide 0.5 mg before each meal 3-4 times a day for 2 years. All subjects had abnormal glucose tolerance.Subjects were randomized to placebo or drug.	Drug: repaglinide; CF pancreatic insufficient patients with impaired glucose tolerance (IGT) or CFRD without fasting hyperglycemia (CFRD-No FH) by OGTT will be treated with repaglinide 0.5 mg before each meal that contains more than 20 grams of carbohydrate 3-4 times a day for 2 years.; Other Names: Prandin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMI		2 year/end of study
Body Composition	Reporting % of Fat and Lean body mass	2 year/end of study
CRP		2 year/end of study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Tolerance	We completed the OGTT at the 2 year/end of study visit.	2-year
Inflammatory Markers		2 year/end of study
Wt Z Score		2 year/end of study
Tanner Stage	Puberty scale measuring 1-5, 1 being least development, 5 being most development.	2 year/end of study
FEV 1	% of lung function	2 year/end of study
C-Peptide		2 year

Collaborators and Investigators

• Sponsor: Arbelaez, Ana Maria
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Novo Nordisk A/S; Washington University School of Medicine; National Institutes of Health (NIH)
• Investigators: Study Chair: Neil H White, M.D., Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: September 29, 2008
• First Submitted That Met QC Criteria: September 30, 2008
• First Posted (Estimate): October 1, 2008

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes; treatment; nutrition; Cystic Fibrosis; Lung function; Pre-diabetes; inflammatory markers; Cystic Fibrosis Related Diabetes; Repaglinide; oral hypoglycemic agents
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Respiratory Tract Diseases; Lung Diseases; Endocrine System Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Hyperglycemia; Pancreatic Diseases; Fibrosis; Diabetes Mellitus; Prediabetic State; Glucose Intolerance; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Hypoglycemic Agents; Physiological Effects of Drugs; Repaglinide
• Other Study ID Numbers: 05-1109; P60DK020579 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The outcome was inconclusive for this hypothesis, but the data may be valuable in future research. We are not currently sharing data from this project.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No