Muscle Accrual and Function in Cystic Fibrosis-Impact of Glucose Intolerance

Completed

• Conditions: Cystic Fibrosis

• Registration Number: NCT02776098
• Lead Sponsor: Children's Hospital of Philadelphia

Brief Summary

This study will investigate the link between glucose abnormalities and elements critical to muscle function including mass, composition and energy metabolism. the primary goal of the study is to determine whether Cystic Fibrosis (CF) disease is associated with muscle dysfunction, especially in the presence of glucose intolerance. This is a longitudinal cohort study of 3 main groups: CF subjects without Cystic Fibrosis-related diabetes (CFRD), healthy matched controls and CF subjects with newly diagnosed CFRD started on insulin therapy.

Detailed Description

Cystic Fibrosis (CF) is a lethal inherited disease that primarily affects the lungs but also confers a high risk of diabetes, with up to 40-50% of adults experiencing Cystic Fibrosis-related diabetes (CFRD). CFRD is associated with an accelerated decline in lung function, nutritional status and survival and despite treatment mortality in patients with CFRD remains high. Airway inflammation and susceptibility to infections caused by hyperglycemia, and the catabolic effect of insulin deficiency are posited mechanisms of CFRD-associated morbidity. Respiratory failure caused by airway disease is well known but the contribution of respiratory muscle dysfunction may be critical. In Type 2 Diabetes Mellitus (T2DM) glucose and insulin defects are closely correlated with muscle function. The pulmonary muscles are crucial to respiration and airway clearance in CF. Muscle function is dependent on its mass, composition, and energy metabolism. Lean body mass (LBM) deficits are present in CF and improvement in LBM improves pulmonary function. Using T2DM as a model for muscle dysfunction, the study hypothesis is that glucose intolerance exacerbates LBM deficits, negatively affects muscle composition, and alters muscle metabolism leading to respiratory muscle dysfunction and a decline in pulmonary function.

CF subjects without CFRD and healthy controls will undergo 3 study visits (baseline then annually for 2 years) and CFRD subjects will undergo 2 study visits (baseline and 6 months after baseline). Evaluations will include neurologic exams, anthropometric assessments, 3-day dietary recall, MRI scans, oral glucose tolerance tests (CF subjects only), blood work, pulmonary function testing, muscle strength testing, exercise testing, bone density scans, and adverse event assessment.

Study Timeline

• Study Start: 2016-05
• Study First Submitted: 2016-05-16
• Study First Submitted QC: 2016-05-16
• Study First Posted: 2016-05-18
• Status Verified: 2024-03
• Primary Completion: 2024-03-04
• Study Completion: 2024-03-04
• Last Update Submitted: 2024-03-06
• Last Update Posted: 2024-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Compare change in mean lean body mass (LBM) from baseline to end of study	24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects

Secondary Outcome Measures

Name	Time	Method
Compare Intramyocellular lipid (IMCL) accumulation from baseline to end of study	24 months (CF without CFRD subjects & healthy controls); 6 months for CF subjects	Proton magnetic resonance spectroscopy will be used to measure IMCL per previously published methods.

Trial Locations

Locations (2)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States