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

NCT04508088 | Recruiting

• 1 other identifier: IRB-P00034878
• Study Type: observational
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Inflammatory Bowel Disease; Crohn Disease

Keywords

Crohn; Bone Marrow; Dual-energy X-ray absorptiometry; Peripheral Quantitative Computed Tomography; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (2)

• Bone marrow adiposity by magnetic resonance imaging (MRI)

  Change in Bone marrow adiposity measured by MRI (T1 maps)

  Baseline and One Year follow-up

• Magnetic resonance spectroscopy (MRS)

  Change in T2 corrected fat/(fat+ water) ratios

  Baseline and One Year follow-up

Secondary Outcomes (12)

• 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

• Spine apparent density Z-score by DXA

  Baseline and One Year follow-up

• Volumetric bone mineral density (vBMD)

  Baseline and One Year follow-up

• Bone strength by quantitative computed tomography pQCT

  Baseline and One Year follow-up

Study Arms (2)

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; Diagnostic Test: Spin-lattice relaxation (T1); Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw

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; Diagnostic Test: Spin-lattice relaxation (T1); Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw

Interventions

Coronal T1 weighted spin echo images DIAGNOSTIC_TEST

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.

Control; Crohn Disease

Spin-lattice relaxation (T1) DIAGNOSTIC_TEST

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.

Control; Crohn Disease

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 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.

Control; Crohn Disease

Blood Draw DIAGNOSTIC_TEST

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; Crohn Disease

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 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

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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) Immune studies: We will first employ bulk RNA-seq on peripheral blood to evaluate molecular gene signatures that correlate with the various bone imaging phenotypes. Molecular markers that correlate with the bone imaging phenotypes will be used to inform development and validation of a CyTOF panel that will be used on matched PBMC samples. Utilizing CyTOF, we will evaluate differences in immune cellular populations between CD patients with normal versus low BMD, and matched controls.

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease

Interventions

Positron-Emission Tomography; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal 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: Rebecca Gordon, MD Attending Physician, Division of Pediatric Endocrinology, MGH; Assistant Professor of Pediatrics, Harvard Medical School

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: August 11, 2020
• Study Start: September 10, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 30, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)