Role of Body Fat Distribution in Metabolic and Pulmonary Decline in Cystic Fibrosis (ORBIT-CF)

Outcomes Related to Body Composition in Teens and Adults With Cystic Fibrosis (ORBIT-CF)

Nutrition and body composition, the amount of muscle and fat in the body, has a role in overall health. This study wants to learn more about how nutrition and body composition affects health outcomes like glucose tolerance and lung function in patients with cystic fibrosis (CF) who are ages 16-30 years old. 60 adolescents and young adults with CF will be recruited, and 30 volunteers without cystic fibrosis. A total of 40 of these study participants with CF will be asked to return for annual study visits for 2 years after the first visit.

The long-term goal of this study is to use the information collected to make decisions about future nutrition monitoring and interventions which help maintain optimal health for individuals with CF.

Study Overview

• Status: Recruiting
• Conditions: Cystic Fibrosis

Detailed Description

This is a prospective, observation study to test the central hypothesis that individuals with cystic fibrosis (CF) have a higher propensity to increased visceral adipose tissue (VAT) accumulation and decreased lean body mass (LBM) compared to healthy controls, and this dysregulation in adipose and protein deposition exacerbates glucose intolerance and lung function decline. A sub-set of participants with CF will be followed longitudinally for two years (n=40). The investigators will conduct detailed body composition, fat distribution, metabolic, and nutritional phenotyping in this cohort. Body fat distribution will be assessed with MRI. Whole body composition will be assessed with DEXA. Glucose tolerance will be assessed with an oral glucose tolerance test (OGTT) and mathematical modeling of the C-peptide and insulin response to glucose. Lung health will be assessed by objective clinical data and self-reported symptoms.

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Jessica A Alvarez, PhD, RD; Phone Number: 4047271390; Email: jessica.alvarez@emory.edu
• Study Contact Backup: Name: Swati Zaveri, PhD; Phone Number: 440-778-8373; Email: swati.shital.zaveri@emory.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Not yet recruiting
      • University of Alabama at Birmingham (UAB)/Children's of Alabama
      • Contact: Michael Stalvey, MD; Phone Number: 205-638-9107
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University/Children's Hospital of Atlanta (CHOA)
      • Contact: Jessica Alvarez, PhD, RD; Phone Number: 404-727-1390; Email: jessica.alvarez@emory.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This will be a two-site study of n=60 patients with CF ages 16 years and older and n=30 age-, sex-, BMI-, and race-matched healthy controls. As a sub-study, 40 of these CF subjects will be followed longitudinally and assessed annually for two years.

Description

Inclusion Criteria:

CF inclusion criteria

1. confirmed CF diagnosis based on sweat testing by pilocarpine iontophoresis and/or cystic fibrosis trans membrane genotyping (CFTR) with two disease causing mutations
2. pancreatic exocrine insufficiency
3. ages 16 years and older
4. clinically stable, defined as no changes in medical regimen (including medications) for at least 21 days prior to study visit
5. baseline FEV1% predicted ≥40% where baseline is defined as the average of the best FEV1% for each quarter of the calendar year
6. participation in the Cystic Fibrosis Foundation (CFF) Patient Registry

Longitudinal study inclusion:

CF participants who have normal glucose tolerance results after their initial study oral glucose tolerance test (OGTT).

Healthy controls inclusion criteria:

1. male or female ages 16 years and older
2. clinically stable. Healthy controls will be recruited who are similar in age, gender, and BMI as the participants with CF.

Exclusion Criteria:

CF exclusion criteria:

1. diagnosis of CF-related diabetes (CFRD)
2. nocturnal tube feeds
3. life expectancy <6 months
4. history of or on waiting list for lung transplant
5. un-removable metal that is incompatible with MRI
6. inability or unwillingness to perform major study activities (OGTT, DEXA, MRI) due to claustrophobia, fear of blood draw, or other reasons
7. current pregnancy or lactation
8. inability to provide informed consent or assent

Healthy controls exclusion criteria:

1. malignant neoplasm (other than localized basal cell cancer of the skin) during the previous 5 years
2. respiratory (including asthma), endocrine (including diabetes), autoimmune, or other chronic disease
3. HIV or other chronic infection
4. current use of any medications to treat an acute or chronic disease or illness
5. acute illness within the past 3 weeks
6. intravenous or oral antibiotics or use of systemic corticosteroids within the past 3 weeks
7. inability or unwillingness to perform major study activities due to claustrophobia, fear of blood draw, or other reasons
8. current pregnancy or lactation
9. inability to provide informed consent or assent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Subjects with Cystic Fibrosis; n=60 patients with CF ages 16-30
Healthy Controls; n=30 healthy controls matched to participants with CF for age, sex, BMI, and race.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visceral Adipose Tissue volume (VAT) by Magnetic Resonance Imaging (MRI)	Body fat distribution and body composition in 60 individuals with Cystic Fibrosis (CF) and 30 matched, healthy control will be assessed by Magnetic Resonance Imaging (MRI)	Baseline, 1 year, 2 year
Change in Disposition Index	The disposition index (DI) is a measure of the ability of B-cells to compensate for insulin resistance. A lower DI indicates a loss of B-cell function, which means decreased pancreatic function. The disposition index will be assessed with an oral glucose tolerance test (OGTT) and mathematical modeling of the C-peptide and insulin response to glucose. This study seeks to determine if glucose intolerance is associated with body composition and fat distribution in CF subjects.	Baseline, 1 year, 2 year
Change in Forced Expiratory Volume in the first second (FEV1%)	Clinical spirometry is a test of lung function that will be used to assess the progression of lung disease with the baseline Forced Expiratory Volume (FEV%) predicted within the past year. Baseline is defined as the average of the best FEV1% for each quarter of the calendar year. FEV1% predicted is a method of determining the severity of pulmonary disease and declines as disease severity increases.	Baseline, 1 year, 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pancreatic lipid	Pancreatic lipid contributes to the Visceral Adipose Tissue volume (VAT) and it will me measured with the magnetic resonance imaging (MRI). Participants will lay in the supine position for approximately 30 minutes while in the MRI scanner, and images of the abdominal area (L1-L5 vertebrae) and thigh area will be obtained. Images will later be analyzed for quantification of VAT volume and lipid content of pancreas will be analyzed	Baseline, 1 year, 2 year
Change in Hepatic lipid	Hepatic lipid contributes to the Visceral Adipose Tissue volume (VAT) and it will me measured with the MRI. Participants will lay in the supine position for approximately 30 minutes while in the MRI scanner, and images of the abdominal area (L1-L5 vertebrae) and thigh area will be obtained. Images will later be analyzed for quantification of VAT volume and lipid content of liver will be analyzed	Baseline, 1 year, 2 year
Change in Thigh perimuscular adipose tissue (PMAT)	Thigh PMAT contributes to the VAT and it will me measured with the MRI. Participants will lay in the supine position for approximately 30 minutes while in the MRI scanner, and images of the abdominal area (L1-L5 vertebrae) and thigh area will be obtained. Images will later be analyzed for quantification of VAT volume and Thigh PMAT	Baseline, 1 year, 2 year
Change in Body Composition Analysis	Dual-energy X-ray absorptiometry (DEXA) is an imaging technique that provides whole body and regional estimates of the three main body components: fat, lean soft tissues and bone mineral mass.	Baseline, 1 year, 2 year
Change in Insulin secretion	Insulin secretion measures the total beta cell response (PhiTot), and will be assessed with an oral glucose tolerance test (OGTT). Fasted blood samples will be drawn 30 minutes and 15 minutes before the initiation of glucose consumption. At time "zero", an oral glucose solution at the dose of 1.75 gm/kg to a maximum of 75 gms will be provided and consumed within 5 minutes of administration. Subsequent blood samples will be drawn at 10, 20, 30, 60, 90, and 120 min following initiation of glucose ingestion. Decreased insulin secretion has been associated with lower B-cell function.	Baseline, 1 year, 2 year
Change in Whole body insulin sensitivity index (WBISI)	Insulin sensitivity describes how sensitive the body is to the effects of insulin. Whole body insulin sensitivity index (WBISI) is derived from glucose and insulin levels from the full length of the OGTT. The index is calculated using a formula. Decreased insulin sensitivity index is associated with more advanced CF disease.	Baseline, 1 year, 2 year
Annual rate of Forced Expiratory Volume in the first second (FEV1%) decline	FEV1 is the maximal amount of air you can forcefully exhale in one second. It is then converted to a percentage of normal, based on your height, weight, and race. It is assessed when doing the spirometry.	Baseline, 1 year, 2 year
Number of pulmonary exacerbations needing intravenous (IV) antibiotics within previous five years	Number of pulmonary exacerbations needing intravenous (IV) antibiotics within previous five years will be recorded.	Baseline
Number of Perceived respiratory symptoms measured with the Cystic Fibrosis Questionnaire-Revised (CFQ-R)	The Cystic Fibrosis Questionnaire-Revised (CFQ-R) is a disease-specific instrument, designed to measure impact on overall health, daily life, perceived well-being and symptoms. Scores range from 0 to 100, with higher scores indicating better health.	Baseline, 1 year, 2 year

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Jessica A Alvarez, PhD, RD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2019
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: June 27, 2019
• First Submitted That Met QC Criteria: June 27, 2019
• First Posted (Actual): July 1, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: IRB00110358

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Completely de-identified participant data will be shared after publication of all results.
• IPD Sharing Time Frame: Beginning 9 months following publication of results. No end date.

IPD Sharing Access Criteria

Researchers who provide a methodologically sound proposal that is approved by all primary study co-investigators.

Types of analyses: To achieve the aims in the approved proposal and for individual participant data-meta analysis.

Proposals should be directed to Dr. Alvarez at jessica.alvarez@emory.edu

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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