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Inflammatory Bowel DiseaseNCT04508088

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

An observational study of Inflammatory Bowel Disease and Crohn Disease, run by Massachusetts General Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 13 to 20 yearsHealthy volunteers can take part
Conditions the study is for
Inflammatory Bowel Disease, Crohn Disease
What is being tested?
Coronal T1 weighted spin echo images, Spin-lattice relaxation (T1) and Magnetic resonance spectroscopy
How many people
92 participants
Where
1 siteUnited States
Study dates
10 Sep 2020to Dec 2026
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 to 20 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

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.

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Rebecca Gordon, MD contact

(617) 355-7476

rebecca.gordon@childrens.harvard.edu

United States1 site, 1 recruiting

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

    Rebecca Gordon, MD

    Recruiting

Other trials in United States

About this study

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.

Read the 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.

Being tested
Coronal T1 weighted spin echo images, Spin-lattice relaxation (T1), Magnetic resonance spectroscopy, Blood Draw
Keywords
Crohn, Bone Marrow, Dual-energy X-ray absorptiometry, Peripheral Quantitative Computed Tomography, Magnetic Resonance Imaging
Medical subject headings
Inflammatory Bowel Diseases, Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Coronal T1 weighted spin echo imagesDiagnostic 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.

  • 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.

  • Magnetic resonance spectroscopyDiagnostic 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.

  • Blood DrawDiagnostic 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.

Study groups in NCT04508088
Study groupRoleWhat they receive
Crohn DiseaseThis 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.
Receives: Diagnostic Test: Coronal T1 weighted spin echo images; Diagnostic Test: Spin-lattice relaxation (T1); Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw
ControlControls 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.
Receives: Diagnostic Test: Coronal T1 weighted spin echo images; Diagnostic Test: Spin-lattice relaxation (T1); Diagnostic Test: Magnetic resonance spectroscopy; Diagnostic Test: Blood Draw

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bone marrow adiposity by magnetic resonance imaging (MRI)

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

    Measured: Baseline and One Year follow-up

  2. Magnetic resonance spectroscopy (MRS)

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

    Measured: Baseline and One Year follow-up

Secondary outcomes (12)

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

    Change in Total body BMD Z-score

    Measured: Baseline and One Year follow-up

  2. Spine BMD Z-score by DXA

    Change in Lumbar spine BMD Z-score

    Measured: Baseline and One Year follow-up

  3. Spine apparent density Z-score by DXA

    Change in Lumbar spine bone mineral apparent density (g/cm3)

    Measured: Baseline and One Year follow-up

  4. Volumetric bone mineral density (vBMD)

    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

    Measured: Baseline and One Year follow-up

  5. Bone strength by quantitative computed tomography pQCT

    Change in PQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate

    Measured: Baseline and One Year follow-up

  6. Bone Formation Marker #1

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

    Measured: Baseline and One Year follow-up

  7. Bone Formation Marker #2

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

    Measured: Baseline and One Year follow-up

  8. Bone Resorption Marker

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

    Measured: Baseline and One Year follow-up

  9. Immune Studies

    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.

    Measured: Baseline and One Year follow-up

  10. Current Crohn's Disease Activity

    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.

    Measured: Baseline and One Year follow-up

  11. Physical Activity

    Physical activity will be assessed through a physical activity questionnaire

    Measured: Baseline and One Year follow-up

  12. Dietary Calcium Intake

    Dietary calcium intake will be assessed through a targeted dietary questionnaire

    Measured: Baseline and One Year follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2020
  2. Study start10 Sep 2020
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case-control
Time perspective
Prospective
Enrolment
92 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04508088
Sponsor's protocol ID
IRB-P00034878
Status last verified
Oct 2025
First submitted
22 Jul 2020
Last updated
30 Oct 2025
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gupta A, Paski S, Issenman R, Webber C. Lumbar spine bone mineral density at diagnosis and during follow-up in children with IBD. J Clin Densitom. 2004 Fall;7(3):290-5. doi: 10.1385/jcd:7:3:290.

    PubMed 15319499

  • Sylvester FA, Wyzga N, Hyams JS, Davis PM, Lerer T, Vance K, Hawker G, Griffiths AM. Natural history of bone metabolism and bone mineral density in children with inflammatory bowel disease. Inflamm Bowel Dis. 2007 Jan;13(1):42-50. doi: 10.1002/ibd.20006.

    PubMed 17206638

  • Schmidt S, Mellstrom D, Norjavaara E, Sundh SV, Saalman R. Low bone mineral density in children and adolescents with inflammatory bowel disease: a population-based study from Western Sweden. Inflamm Bowel Dis. 2009 Dec;15(12):1844-50. doi: 10.1002/ibd.20962. Epub 2009 Apr 30.

    PubMed 19408319

  • Werkstetter KJ, Pozza SB, Filipiak-Pittroff B, Schatz SB, Prell C, Bufler P, Koletzko B, Koletzko S. Long-term development of bone geometry and muscle in pediatric inflammatory bowel disease. Am J Gastroenterol. 2011 May;106(5):988-98. doi: 10.1038/ajg.2010.495. Epub 2011 Jan 11.

    PubMed 21224841

  • Bechtold S, Alberer M, Arenz T, Putzker S, Filipiak-Pittroff B, Schwarz HP, Koletzko S. Reduced muscle mass and bone size in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010 Feb;16(2):216-25. doi: 10.1002/ibd.21021.

    PubMed 19637389

  • Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB. Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn's disease. Gastroenterology. 2009 Jan;136(1):123-30. doi: 10.1053/j.gastro.2008.09.072. Epub 2008 Nov 1.

    PubMed 19026647

  • Bonjour JP, Theintz G, Law F, Slosman D, Rizzoli R. Peak bone mass. Osteoporos Int. 1994;4 Suppl 1:7-13. doi: 10.1007/BF01623429.

    PubMed 8081064

  • Tuchman S, Thayu M, Shults J, Zemel BS, Burnham JM, Leonard MB. Interpretation of biomarkers of bone metabolism in children: impact of growth velocity and body size in healthy children and chronic disease. J Pediatr. 2008 Oct;153(4):484-90. doi: 10.1016/j.jpeds.2008.04.028. Epub 2008 Jun 16.

    PubMed 18555484

  • Waitches G, Zawin JK, Poznanski AK. Sequence and rate of bone marrow conversion in the femora of children as seen on MR imaging: are accepted standards accurate? AJR Am J Roentgenol. 1994 Jun;162(6):1399-406. doi: 10.2214/ajr.162.6.8192007.

    PubMed 8192007

  • Taccone A, Oddone M, Dell'Acqua AD, Occhi M, Ciccone MA. MRI "road-map" of normal age-related bone marrow. II. Thorax, pelvis and extremities. Pediatr Radiol. 1995;25(8):596-606. doi: 10.1007/BF02011826.

    PubMed 8570312

  • Taccone A, Oddone M, Occhi M, Dell'Acqua AD, Ciccone MA. MRI "road-map" of normal age-related bone marrow. I. Cranial bone and spine. Pediatr Radiol. 1995;25(8):588-95. doi: 10.1007/BF02011825.

    PubMed 8570311

  • Thayu M, Leonard MB, Hyams JS, Crandall WV, Kugathasan S, Otley AR, Olson A, Johanns J, Marano CW, Heuschkel RB, Veereman-Wauters G, Griffiths AM, Baldassano RN; Reach Study Group. Improvement in biomarkers of bone formation during infliximab therapy in pediatric Crohn's disease: results of the REACH study. Clin Gastroenterol Hepatol. 2008 Dec;6(12):1378-84. doi: 10.1016/j.cgh.2008.07.010.

    PubMed 19081527

  • Thornton D, Gordon CM. Restrictive Eating Disorders and Skeletal Health in Adolescent Girls and Young Women. Calcif Tissue Int. 2017 May;100(5):449-460. doi: 10.1007/s00223-016-0164-0. Epub 2016 Jun 23.

    PubMed 27339670

  • Ecklund K, Vajapeyam S, Feldman HA, Buzney CD, Mulkern RV, Kleinman PK, Rosen CJ, Gordon CM. Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res. 2010 Feb;25(2):298-304. doi: 10.1359/jbmr.090805.

    PubMed 19653811

  • Ecklund K, Vajapeyam S, Mulkern RV, Feldman HA, O'Donnell JM, DiVasta AD, Gordon CM. Bone marrow fat content in 70 adolescent girls with anorexia nervosa: Magnetic resonance imaging and magnetic resonance spectroscopy assessment. Pediatr Radiol. 2017 Jul;47(8):952-962. doi: 10.1007/s00247-017-3856-3. Epub 2017 Apr 22.

    PubMed 28432403

Questions about this trial

What is this clinical trial studying?

An observational study of Inflammatory Bowel Disease and Crohn Disease, run by Massachusetts General Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Rebecca Gordon, MD ((617) 355-7476, rebecca.gordon@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bone marrow adiposity by magnetic resonance imaging (MRI) (time frame: Baseline and One Year follow-up). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04508088, which also lists 53 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2025.

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