CFTR Modulator Effects on Bone and Muscle in Adults With Cystic Fibrosis

Study is looking at the effects of cystic fibrosis treatment on bone muscle.

Study Overview

• Status: Active, not recruiting
• Conditions: Cystic Fibrosis; Bone Loss; Muscle Loss
• Intervention / Treatment: Drug: Cftr Modulators

Detailed Description

Cystic fibrosis (CF) is a complex multisystem genetic disease, with pulmonary and gastrointestinal consequences dominating the clinical picture. The life-expectancy of CF patients has increased through several therapeutic advances. Although respiratory failure remains the major cause of mortality in CF, musculoskeletal impairments contribute to major morbidity. In the general population, musculoskeletal conditions are among the most common reasons for seeking medical care, and the risk of osteoporotic fracture increases with age. As the CF population ages, the morbidity related to musculoskeletal effects may increase.

The etiology of CF related bone disease is multifactorial and includes effects of pancreatic insufficiency, poor nutritional status, vitamin D deficiency, glucocorticoid treatment, inflammation, hypogonadism, and sarcopenia, collectively resulting in attenuated bone mineral accrual and low bone density The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulating drugs on bone disease in CF has not been evaluated. Effects of CFTR modulators may help counter the bone and muscle consequences of CF either directly by effects on bone or muscle cells, or indirectly by improved lung disease, improved nutritional status, decreased systemic inflammation or glucocorticoid use, or subsequent increases in physical activity.

The rationale that underlies the proposed research is that better understanding of the bone and muscle effects of CFTR modulator therapies will help guide strategies to optimize bone accrual, prevent osteoporosis and fractures, and improve functional outcomes in the aging CF population. Set on the backbone of a longitudinal observational cohort study, the study will systematically and comprehensively evaluate changes in bone and muscle mass and strength from baseline to 12 month and 24 month time points among patients receiving CFTR modulator therapies and also among controls not receiving CFTR modulator therapies.

• Study Type: Observational
• Enrollment (Actual): 63

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5149
      • Indiana University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Enrollment will target groups that are frequency matched for age (decade), race, sex, pancreatic insufficiency and glucocorticoid usage (inhaled or systemic as both have skeletal effects in some studies) to control for these factors influencing relevant bone and muscle outcomes. (see statistical description). The study will enroll up to 30 subjects in each group, expecting up to 25% dropout.

Description

Inclusion Criteria:

• documented, confirmed diagnosis of CF

  • Age ≥18 years old
  • >21 days since the start of their last pulmonary exacerbation at the baseline visit
  • Provide signed written informed consent to participate

Exclusion Criteria:

• • Estimated glomerular filtration rate (eGFR) <30 ml/min/m2 using the CKD-EPI equation,

  • Treatment with any osteoporosis medication within 6 months for oral agents or 1 year for intravenous or injectable agents (Subjects may participate if therapy stopped earlier than these time periods).
  • Current treatment with growth hormone or IGF-1
  • Currently pregnant or lactating or planning plan on becoming pregnant during the duration of the study.
  • Life expectancy less than 12 months
  • History of lung transplantation
  • Conditions that in the opinion of the investigators would interfere with the ability to collect or interpret the data, or put the patient at higher safety risk from study procedures.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
on CFTR; For patients on or near time of initiation CFTR modulator therapy	Drug: Cftr Modulators; CFTR modulators are drugs used to treat cystic fibrosis
Controls; controls will be patients not eligible for available treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify the effects of CFTR modulators on bone mineral density	Changes from baseline to 12 month in total volumetric BMD and in estimated failure load as measured by HRpQCT at the distal radius and tibia	12 months
establish the effect of CFTR modulators on sarcopenia.	changes from baseline to 12 months in whole body lean mass using body composition software on DXA	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify the effect of CFTR modulators on bone mineral density	Changes from baseline to 24 month in total volumetric BMD and in estimated failure load as measured by HRpQCT at the distal radius and tibia. Changes from baseline to 6, 12, and 24 month in HRpQCT measure of cortical vBMD and trabecular vBMD at both the distal radius and tibia and cortical vBMD and trabecular vBMD at diaphyseal site. Changes from baseline to 6, 12 and 24 month in HRpQCT measure of cortical vBMC and trabecular vBMD at both the distal radius and tibia and cortical vBMD at a diaphyseal site Changes from baseline to 6,12, and 24 month in areal BMD using DXA at eh lumbar spine, total body, femur neck and total hip	6, 12 and 24 month
establish the effect of CFTR modulators on sarcopenia.	changes from baseline to 6 and 24 months in whole body lean mass using body composition software on DXA Changes from baseline to 6, 12, 24 months in appendicular lean mass relative to height measured using body composition software on DXA	6, 12 and 24 month

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Cystic Fibrosis Foundation
• Investigators: Principal Investigator: Erik A Imel, MD, Indiana University

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2019
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 18, 2019
• First Submitted That Met QC Criteria: December 18, 2019
• First Posted (Actual): December 20, 2019

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Bone Diseases; Musculoskeletal Diseases; Nervous System Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Genetic Diseases, Inborn; Metabolic Diseases; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Muscular Atrophy; Cystic Fibrosis; Bone Diseases, Metabolic
• Other Study ID Numbers: 1908566174

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No