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

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

Detailed Description
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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.

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

Conditions
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Cystic Fibrosis, Bone Loss, Muscle Loss

Intervention / Treatment
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* Drug: Cftr Modulators


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| on CFTR<br>For patients on or near time of initiation CFTR modulator therapy | Drug: Cftr Modulators<br>* CFTR modulators are drugs used to treat cystic fibrosis<br>|
| Controls<br>controls will be patients not eligible for available treatment | |

What is the study measuring?
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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 |