Redox Imbalance and the Development of Cystic Fibrosis Diabetes

NCT02202876 | Completed

• 1 other identifier: IRB00060962
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Cystic fibrosis-related diabetes (CFRD) occurs in almost 20% of teens and 50% of adults. The investigators' long term goal is to determine the cause of CFRD in order to translate this knowledge into therapies aimed at preventing CFRD. Since CFRD and type 2 diabetes share several clinical features and since oxidative stress is a key factor in the development of type 2 diabetes, the investigators explored the role of oxidative stress in CFRD. The investigators discovered a unique CF biochemical signature that they believe could be implicated in the development of CFRD. The investigators found that glucose ingestion in CF teens and young adults causes an acute and profound systemic redox imbalance to the oxidizing state. The degree of redox imbalance was quite severe and would be expected to damage the insulin producing cells as these cells are particularly vulnerable to oxidative stress. Thus, these findings could prove to be a critical factor in the pathogenesis of CFRD. This proposal will test the hypothesis that glucose-induced redox imbalance is an intrinsic, metabolic defect in CF. In addition, because CF people are required to consume a high calorie diet to maintain their weight, the investigators also hypothesize that certain high caloric foods will recapitulate the redox imbalance induced by ingesting glucose and thus hasten the development of CFRD. Specifically, the investigators aim to:

• Determine whether young children with CF have glucose-induced redox imbalance
• Determine whether eating a meal with a high glycemic index induces acute redox imbalance
• Determine whether commonly consumed beverages containing simple sugars (i.e., soda or fruit juice) induce acute redox imbalance

Conditions

Diabetes Mellitus, Type 2; Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Acute oxidation

  cysteine/cysteine ratio

  Up to three hours

Study Arms (6)

Aim 1: Children with Cystic Fibrosis

ACTIVE COMPARATOR

Cystic Fibrosis children aged 1 to 9 years with normal glucose tolerance receiving Oral Glucose Tolerance Test

Other: Oral Glucose Tolerance Test

Aim 1: Control Children

ACTIVE COMPARATOR

Children with out Cystic Fibrosis aged 1 to 9 years controls with normal glucose tolerance receiving Oral Glucose Tolerance Test

Other: Oral Glucose Tolerance Test

Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal

ACTIVE COMPARATOR

Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating High Glycemic Index Meal

Other: High Glycemic Index Meal

Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal

ACTIVE COMPARATOR

Cystic Fibrosis subjects 12 years of age or older with normal glucose tolerance eating Low Glycemic Index Meal

Other: Low Glycemic Index Meal

Aim 2b: Cystic Fibrosis Consuming Test Soda

ACTIVE COMPARATOR

Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of a test soda. A week later these participants will have an Oral Glucose Tolerance Test.

Other: Oral Glucose Tolerance Test; Other: Test Soda

Aim 2b: Cystic Fibrosis Consuming Fruit Juice

ACTIVE COMPARATOR

Participants with Cystic Fibrosis 12 years of age or older with normal glucose tolerance or impaired glucose tolerance consuming a test beverage of fruit juice. A week later these participants will have an Oral Glucose Tolerance Test.

Other: Oral Glucose Tolerance Test; Other: Fruit juice

Interventions

Oral Glucose Tolerance Test OTHER

1.75 gm/kg to a maximum of 75 gm of an oral glucose solution

Also known as: OGTT

Aim 1: Children with Cystic Fibrosis; Aim 1: Control Children; Aim 2b: Cystic Fibrosis Consuming Fruit Juice; Aim 2b: Cystic Fibrosis Consuming Test Soda

High Glycemic Index Meal OTHER

isocaloric breakfasts - set the high glycemic index to 80 The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat

Aim 2a: Teens with Cystic Fibrosis - High Glycemic Meal

Low Glycemic Index Meal OTHER

isocaloric breakfasts - set the low glycemic index to 30 The nutrient composition of each meal will be 10 kcal per kg, 50% kcal from carbohydrates, 20% kcal from protein, and 30% kcal from fat

Aim 2a: Teens with Cystic Fibrosis - Low Glycemic Meal

Test Soda OTHER

Test soda containing 60% fructose and 40% glucose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams.

Aim 2b: Cystic Fibrosis Consuming Test Soda

Fruit juice OTHER

Fruit juice containing a combination fructose, glucose, and sucrose at a dose of 1.75 grams per kilogram body weight to a maximum of 75 grams

Aim 2b: Cystic Fibrosis Consuming Fruit Juice

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• For CF children with class I-III mutations
• CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation analysis
• CFTR mutation analysis showing two Class I to III mutations
• Aged 1-9 years
• On a clinically stable medical regimen for at least three weeks
• No IV or oral antibiotics for a respiratory exacerbation for at least three weeks
• No hospitalization for at least six weeks
• For CF children with class IV-VI mutations
• CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation analysis
• CFTR mutation analysis showing at least one Class IV-VI mutation
• Aged 1-9 years
• On a clinically stable medical regimen for at least three weeks
• No IV or oral antibiotics for a respiratory exacerbation for at least three weeks
• No hospitalization for at least six weeks
• Not taking pancreatic enzyme replacement therapy

You may not qualify if:

• Current or past diagnosis of CFRD (for CF children)
• Parents unwilling to have an IV inserted for blood draws
• Aim 2a
• CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation analysis
• CFTR mutation analysis showing two Class I to III mutations
• Aged 12 years or older
• On a clinically stable medical regimen for at least three weeks
• No IV or oral antibiotics for a respiratory exacerbation for at least three weeks
• Current or past diagnosis of CFRD
• Allergy or intolerance to egg or dairy products
• Aim 2b
• CF diagnosed by pilocarpine electrophoresis sweat test and/or CFTR genetic mutation analysis
• CFTR mutation analysis showing two Class I to III mutations
• Aged 12 years or older
• On a clinically stable medical regimen for at least three weeks

Sponsors & Collaborators

• Emory University: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

Children's Healthcare of Atlanta and Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Cystic Fibrosis

Interventions

Glucose Tolerance Test; Fruit and Vegetable Juices

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Endocrine; Investigative Techniques; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Arlene Stecenko, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 25, 2014
• First Posted: July 29, 2014
• Study Start: November 1, 2014
• Primary Completion: September 9, 2018
• Study Completion: September 9, 2018
• Last Updated: June 4, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)