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Skeletal Health and Bone Marrow Composition in Adolescents With Cystic Fibrosis

Recruiting
Conditions
Cystic Fibrosis
Interventions
Diagnostic Test: Magnetic resonance relaxometry
Diagnostic Test: Magnetic resonance spectroscopy
Diagnostic Test: Blood Draw
Diagnostic Test: DXA
Diagnostic Test: pQCT
Registration Number
NCT06216704
Lead Sponsor
Boston Children's Hospital
Brief Summary

The investigators will be evaluating bone marrow composition via magnetic resonance imaging in adolescents diagnosed with cystic fibrosis (CF) compared to healthy, matched controls. The investigators will also be assessing their bone mineral density via other imaging modalities, including dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT). This longitudinal project will focus on abnormalities in bone marrow composition, and specifically whether adolescents with diagnosed with CF exhibit increased bone marrow fat, its association with bone mineral density (BMD) and the underlying pathophysiology, including glycemic control, inflammation, and bone turnover markers.

Detailed Description

Less than optimal bone health has been seen in children that have cystic fibrosis (CF). This can present as low bone density or altered bone structure, weakening the bones and increasing fragility and fracture risk. As adolescence is especially important in bone development, conditions such as CF during this time can lead to long term bone issues. The underlying mechanisms are not well understood, but what is known is that red bone marrow converts to fat-rich yellow marrow. This study aims to focus on abnormalities in bone marrow, and specifically whether adolescents who have been diagnosed with CF have more bone marrow fat.

The primary hypothesis is that patients with CF will have associated increased fat levels in bone marrow, which will be associated with decreased bone formation and suboptimal bone health. The central objective is to obtain longitudinal data on the differences in bone marrow between patients with CF versus healthy adolescents. Long term, the investigators want to study how abnormal marrow fat and suboptimal bone health relate to one another.

The study involves 36 adolescents diagnosed with CF and 36 matched healthy controls. Eligibility criteria include no other chronic diseases that affect bone health and limited use of bone altering medications in the prior three months. The adolescents with CF will be matched with healthy adolescents based on sex, ancestry, age, and pubertal stage. Additional data on participants with CF will be collected via a chart review that will enable us to more fully characterize their CF.

Imaging will include: MRI of the knee with quantitative marrow fat assessment; dual-energy X-ray absorptiometry (DXA); and peripheral quantitative computed tomography (pQCT). All scans will be for research purposes only. The MRIs will be evaluated for any incidental findings, and if any identified, it will be reported to their primary care physician.

Additionally, blood draws will be used to assess markers of bone formation/resorption and inflammation. In participants with CF, they will have a continuous glucose monitor to assess dysglycemia. All participants will also complete questionnaires.

There will be a baseline visit, and then a follow up visit 1 year later, with identical study procedures at both visits.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
36
Inclusion Criteria
  • 13-20 years old
  • Cystic fibrosis with pancreatic insufficiency
  • Must have a stable treatment regimen, including CFTR modulator usage unchanged for the prior three months
  • Liver transplant recipients will be eligible, as long as they are at least 1 year post-transplant and are no longer on Prednisone for immunosuppressive therapy
Exclusion Criteria
  • Diagnosis of other chronic disease affecting bone health
  • Active use (within the past 3 months) of medications that are known to affect skeletal metabolism
  • CF exacerbation or glucocorticoid exposure within the prior 1 month
  • Lung transplant

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Cystic FibrosisMagnetic resonance spectroscopyThis group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
ControlMagnetic resonance relaxometryControls will be matched for age, Tanner staging, BMI percentile, and ancestry. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
ControlpQCTControls will be matched for age, Tanner staging, BMI percentile, and ancestry. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Cystic FibrosisBlood DrawThis group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
ControlMagnetic resonance spectroscopyControls will be matched for age, Tanner staging, BMI percentile, and ancestry. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
ControlBlood DrawControls will be matched for age, Tanner staging, BMI percentile, and ancestry. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Cystic FibrosisMagnetic resonance relaxometryThis group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Cystic FibrosisDXAThis group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Cystic FibrosispQCTThis group will be 36 adolescents, ages 13-20 years old, who have been diagnosed with cystic fibrosis. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
ControlDXAControls will be matched for age, Tanner staging, BMI percentile, and ancestry. All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Primary Outcome Measures
NameTimeMethod
Bone marrow adiposity by magnetic resonance relaxometry (MR relaxometry)Baseline and One Year follow-up

Change in bone marrow adiposity measured by MR relaxometry

Bone marrow adiposity by magnetic resonance spectroscopy (MRS)Baseline and One Year follow-up

Change in bone marrow adiposity measured by MRS

Secondary Outcome Measures
NameTimeMethod
c-telopeptideBaseline and One Year follow-up

Change in bone resorption assessed by c-telopeptide (pg/ml)

Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)Baseline and One Year follow-up

Change in total body less head BMD Z-score

Hip BMD Z-score by DXABaseline and One year follow-up

Change in hip BMD Z-score

Volumetric bone mineral density (vBMD)Baseline and One Year follow-up

Change in quantitative computed tomography (pQCT) scans will be obtained at the left tibia

Spine BMD Z-score by DXABaseline and One Year follow-up

Change in lumbar spine BMD Z-score

polar strength strain indexBaseline and One Year follow-up

Change in pQCT bone strength measure

osteocalcinBaseline and One Year follow-up

Change in bone formation assessed by osteocalcin (ng/mL)

procollagen type 1 N-terminal propeptideBaseline and One Year follow-up

Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL)

Trial Locations

Locations (1)

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

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