Skeletal Health and Bone Marrow Composition in Adolescents With Cystic Fibrosis

NCT06216704 | Recruiting

• 2 other identifiers: IRB-P00047144005960A123
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Bone Marrow; Dual-energy X-ray absorptiometry; Peripheral Quantitative Computed Tomography; Magnetic Resonance Imaging; pediatrics; bone health

Outcome Measures

Primary Outcomes (2)

• Bone marrow adiposity by magnetic resonance relaxometry (MR relaxometry)

  Change in bone marrow adiposity measured by MR relaxometry

  Baseline and One Year follow-up

• Bone marrow adiposity by magnetic resonance spectroscopy (MRS)

  Change in bone marrow adiposity measured by MRS

  Baseline and One Year follow-up

Secondary Outcomes (8)

• Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)

  Baseline and One Year follow-up

• Spine BMD Z-score by DXA

  Baseline and One Year follow-up

• Hip BMD Z-score by DXA

  Baseline and One year follow-up

• Volumetric bone mineral density (vBMD)

  Baseline and One Year follow-up

• polar strength strain index

  Baseline and One Year follow-up

Study Arms (2)

Cystic Fibrosis

This 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.

Diagnostic Test: Magnetic resonance relaxometry; Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw; Diagnostic Test: DXA; Diagnostic Test: pQCT

Control

Controls 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.

Diagnostic Test: Magnetic resonance relaxometry; Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw; Diagnostic Test: DXA; Diagnostic Test: pQCT

Interventions

Magnetic resonance relaxometry DIAGNOSTIC_TEST

Spin-lattice relaxation (T1) relaxometry acquisition consisting of fast spin echo (FSE) acquisitions through the knee. T1 maps from the T1 relaxometry images will be generated using a two-parameter-fit iterative algorithm developed in-house using IDL software (Harris Geospatial Solutions, Melbourne, FL, USA). Mean T1 values for each region will be recorded. The anatomical locations of these regions will be consistent in size for all subjects and location. The locations chosen for the primary endpoints are ones that are known to be rich in red and yellow marrow, respectively.

Control; Cystic Fibrosis

Magnetic resonance spectroscopy DIAGNOSTIC_TEST

Magnetic resonance spectroscopy. MRS will be performed within a 1 mL voxel situated in the medial aspect of the distal femoral metaphysis. A single voxel point resolved spectral acquisition (PRESS) technique will be used to acquire non-water suppressed spectra at multiple echo times. Spectral fits using JMRUI MRS processing software (www.jmrui.eu) to the water and methylene/methyl resonances will be used to quantify peak areas and establish T2 corrected fat/(fat + water) ratios.

Control; Cystic Fibrosis

Blood Draw DIAGNOSTIC_TEST

Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and inflammation. Specific markers of bone formation that will be assessed include osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP), and a marker of bone resorption, c-telopeptide (CTX). Additionally, in participants with CF, we will assess inflammation, with a c-reactive protein (CRP), and dysglycemia, with a continuous glucose monitor.

Control; Cystic Fibrosis

DXA DIAGNOSTIC_TEST

DXA will be utilized to obtain BMD of the total body, lumbar spine, and hip using a Hologic Horizon densitometer (Hologic Inc, Bedford, MA). Body composition will be obtained from total body scans.

Control; Cystic Fibrosis

pQCT DIAGNOSTIC_TEST

pQCT will be utilized to obtain volumetric BMD (mg/cm3) of the left tibia. Measurements using a Stratec XCT 3000 device (Orthometrix, White Plains, NY) will be obtained at multiple locations, in relation to distal growth plate.

Control; Cystic Fibrosis

Eligibility Criteria

• Age: 13 Years - 20 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

The experimental group will be adolescents aged 13-20 with CF. The control group will be matched for sex, ancestry, age (within 2 years), and pubertal stage (based on Tanner staging, ± 1 Tanner stage).

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Cystic Fibrosis Foundation: collaborator

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (26)

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Biospecimen

Retention: SAMPLES WITHOUT DNA

A) Bone turnover markers: We will assess markers of bone formation, including osteocalcin (OC) and procollagen type 1 N-terminal propeptide (P1NP), and a marker of bone resorption, c-telopeptide (CTX). B) Inflammation: We will assess CRP. C) In participants with CF, we will assess dysglycemia with a continuous glucose monitor.

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

Positron-Emission Tomography; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rebecca Gordon, MD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Gordon, MD

CONTACT

(617) 355-7476; rebecca.gordon@childrens.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Physician, Division of Pediatric Endocrinology, MGH; Assistant Professor of Pediatrics, Harvard Medical School

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 22, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)