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

Not Applicable

Completed

Conditions: Cystic Fibrosis Related Diabetes
Pancreatic Insufficiency

Interventions: Drug: repaglinide
Drug: placebo

Registration Number: NCT00763412

Lead Sponsor: Arbelaez, Ana Maria

Brief Summary: 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.

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 31

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2. repaglinide	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.
1 Placebo	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.

Primary Outcome Measures

Name	Time	Method
Body Composition	2 year/end of study	Reporting % of Fat and Lean body mass
BMI	2 year/end of study
CRP	2 year/end of study

Secondary Outcome Measures

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