Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease

January 10, 2024 updated by: Rebecca Gordon, Boston Children's Hospital
The investigators will be evaluating bone marrow composition via magnetic resonance imaging in newly diagnosed adolescents with Crohn disease (CD) 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 and peripheral quantitative computed tomography. This longitudinal project will focus on abnormalities in bone marrow composition, and specifically whether adolescents with newly diagnosed CD exhibit increased bone marrow fat, its association with bone mineral density (BMD) and the underlying pathophysiology, including bone turnover markers and immune cellular/molecular parameters.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Less than optimal bone health has been seen in children that have inflammatory bowel disease (IBD), including Crohn disease (CD). 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 CD 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 CD have more bone marrow fat.

The primary hypothesis is that newly diagnosed CD is associated with increased fat levels in bone, which is associated with decreased bone formation and suboptimal bone health. The central objective is to obtain longitudinal data on the differences in bone marrow between healthy adolescents and those with CD. Long term, the investigators want to study how abnormal fat tissue and suboptimal bone health relate to each other.

The study involves 46 adolescents recently diagnosed with CD and 46 healthy adolescents. Eligibility criteria include no other chronic diseases that affect bone health and limited use of bone altering medications in the last three months. The CD adolescents will be matched with healthy adolescents based on age, stage of puberty, and BMI percentile. Additional data on CD participants will be collected via a chart review that will enable us to more fully characterize their CD.

Imaging will include MRIs of the knee. Measurements will include a visual assessment and quantitative marrow fat analysis, 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 abnormalities, and if there is an incidental finding, it will be reported to the primary care physician.

Additionally, blood draws will be used to attain and assess markers of bone formation/resorption and to perform immune studies.

Study Type

Observational

Enrollment (Estimated)

92

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Boston Children's Hospital
        • Contact:
          • Rebecca Gordon, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The experimental group will be adolescents aged 13-20 with newly diagnosed CD (within 3 months of diagnosis, based on histologic diagnosis and verified with their gastroenterologist).

The control group will be matched for age (within 1 year), pubertal stage (based on Tanner staging), and BMI percentile. Tanner staging will be based on clinically documented Tanner stage by GI physician for participants with CD and by their primary care physician for control participants. If there is no documented Tanner staging, then it will either be performed by the participants primary care physician, or by a pediatric endocrinologist.

Description

Inclusion Criteria:

  • Crohn's Disease diagnosed within the past 3 months, or a healthy, matched control

Exclusion Criteria:

  • Participants with chronic disease known to affect skeletal metabolism
  • Participants on certain medications within the prior 3 months that are known to affect skeletal metabolism
  • Participants who are pregnant
  • Participants who have a history of: claustrophobia, internal body metal that is not compatible with MRI machine, or a known abnormality on or adjacent to the left knee

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Crohn Disease

This group will be 46 adolescents, ages 13-20, who have been recently (within 3 months) diagnosed with Crohn Disease.

All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Diagnostic test: Coronal T1 weighted spin echo images
Coronal T1 weighted spin echo images will be obtained through the knee with a field of view of 16cm to include distal femoral and proximal tibial metaphyses.
Diagnostic test: Spin-lattice relaxation (T1)
Spin-lattice relaxation (T1) relaxometry acquisition consisting of seven 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.
Diagnostic test: Magnetic resonance spectroscopy
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 echo times of 20, 30, 40, and 50 ms using 32 signal averages per echo time with a TR of 2.5 s (total scan time = 5.4 minutes). 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.
Diagnostic test: Blood Draw
Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and to perform immune studies. 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). We will also evaluate molecular gene signatures from the blood samples that correlate with the previously described bone imaging phenotypes. At that point, the information will be used to develop a CyTOF panel to evaluate differences in immune cellular populations between CD patients with normal versus low BMD, and matched controls.
Control

Controls will be matched for age, Tanner staging, and BMI percentile.

All participants will have a two study visits approximately one year apart during which the listed diagnostic testing will be performed.
Diagnostic test: Coronal T1 weighted spin echo images
Coronal T1 weighted spin echo images will be obtained through the knee with a field of view of 16cm to include distal femoral and proximal tibial metaphyses.
Diagnostic test: Spin-lattice relaxation (T1)
Spin-lattice relaxation (T1) relaxometry acquisition consisting of seven 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.
Diagnostic test: Magnetic resonance spectroscopy
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 echo times of 20, 30, 40, and 50 ms using 32 signal averages per echo time with a TR of 2.5 s (total scan time = 5.4 minutes). 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.
Diagnostic test: Blood Draw
Blood draw. Blood draws will be used to attain and assess markers of bone formation/resorption and to perform immune studies. 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). We will also evaluate molecular gene signatures from the blood samples that correlate with the previously described bone imaging phenotypes. At that point, the information will be used to develop a CyTOF panel to evaluate differences in immune cellular populations between CD patients with normal versus low BMD, and matched controls.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bone marrow adiposity by magnetic resonance imaging (MRI)
Time Frame: Baseline and One Year follow-up
Change in Bone marrow adiposity measured by MRI (T1 maps)
Baseline and One Year follow-up
Magnetic resonance spectroscopy (MRS)
Time Frame: Baseline and One Year follow-up
Change in T2 corrected fat/(fat+ water) ratios
Baseline and One Year follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)
Time Frame: Baseline and One Year follow-up
Change in Total body BMD Z-score
Baseline and One Year follow-up
Spine BMD Z-score by DXA
Time Frame: Baseline and One Year follow-up
Change in Lumbar spine BMD Z-score
Baseline and One Year follow-up
Spine apparent density Z-score by DXA
Time Frame: Baseline and One Year follow-up
Change in Lumbar spine bone mineral apparent density (g/cm3)
Baseline and One Year follow-up
Volumetric bone mineral density (vBMD)
Time Frame: Baseline and One Year follow-up
Change in Quantitative computed tomography (pQCT) scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate
Baseline and One Year follow-up
Bone strength by quantitative computed tomography pQCT
Time Frame: Baseline and One Year follow-up
Change in PQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate
Baseline and One Year follow-up
Bone Formation Marker #1
Time Frame: Baseline and One Year follow-up
Change in bone formation assessed by osteocalcin (ng/mL)
Baseline and One Year follow-up
Bone Formation Marker #2
Time Frame: Baseline and One Year follow-up
Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL)
Baseline and One Year follow-up
Bone Resorption Marker
Time Frame: Baseline and One Year follow-up
Change in bone resorption assessed by c-telopeptide (pg/ml)
Baseline and One Year follow-up
Immune Studies
Time Frame: Baseline and One Year follow-up
Bulk RNA-sequencing on peripheral blood to evaluate molecular gene signatures that correlate with various bone imaging phenotypes; these will then be used to inform development and validation of a Mass Cytometry by Time-of-Flight panel that will be used on matched peripheral blood mononuclear cells samples.
Baseline and One Year follow-up
Current Crohn's Disease Activity
Time Frame: Baseline and One Year follow-up
Current Crohn's disease activity will be assessed using the pediatric Crohn disease activity index (PCDAI). The assessment will be made based on questionnaires answered.
Baseline and One Year follow-up
Physical Activity
Time Frame: Baseline and One Year follow-up
Physical activity will be assessed through a physical activity questionnaire
Baseline and One Year follow-up
Dietary Calcium Intake
Time Frame: Baseline and One Year follow-up
Dietary calcium intake will be assessed through a targeted dietary questionnaire
Baseline and One Year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boston Children's Hospital

Investigators

  • Principal Investigator: Rebecca Gordon, MD, Boston Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 10, 2020

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

July 22, 2020

First Submitted That Met QC Criteria

August 9, 2020

First Posted (Actual)

August 11, 2020

Study Record Updates

Last Update Posted (Actual)

January 11, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-P00034878

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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