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

Crohn Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04508088
• Other study ID #: IRB-P00034878
• Status: Recruiting
• Start date: September 10, 2020
• Est. completion date: December 2024

Study information

• Verified date: January 2024
• Source: Boston Children's Hospital
• Contact: Rebecca Gordon, MD
• Phone: (617) 355-7476
• Email: rebecca.gordon[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 13 Years to 20 Years

Eligibility

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

Related Conditions & MeSH terms

• Crohn Disease
• Inflammatory Bowel Disease
• Inflammatory Bowel Diseases

Intervention

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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Boston Children's Hospital

Country where clinical trial is conducted

United States, 

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* Note: There are 53 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone marrow adiposity by magnetic resonance imaging (MRI)	Change in Bone marrow adiposity measured by MRI (T1 maps)	Baseline and One Year follow-up
Primary	Magnetic resonance spectroscopy (MRS)	Change in T2 corrected fat/(fat+ water) ratios	Baseline and One Year follow-up
Secondary	Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)	Change in Total body BMD Z-score	Baseline and One Year follow-up
Secondary	Spine BMD Z-score by DXA	Change in Lumbar spine BMD Z-score	Baseline and One Year follow-up
Secondary	Spine apparent density Z-score by DXA	Change in Lumbar spine bone mineral apparent density (g/cm3)	Baseline and One Year follow-up
Secondary	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	Baseline and One Year follow-up
Secondary	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	Baseline and One Year follow-up
Secondary	Bone Formation Marker #1	Change in bone formation assessed by osteocalcin (ng/mL)	Baseline and One Year follow-up
Secondary	Bone Formation Marker #2	Change in bone formation assessed by procollagen type 1 N-terminal propeptide (ng/mL)	Baseline and One Year follow-up
Secondary	Bone Resorption Marker	Change in bone resorption assessed by c-telopeptide (pg/ml)	Baseline and One Year follow-up
Secondary	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.	Baseline and One Year follow-up
Secondary	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.	Baseline and One Year follow-up
Secondary	Physical Activity	Physical activity will be assessed through a physical activity questionnaire	Baseline and One Year follow-up
Secondary	Dietary Calcium Intake	Dietary calcium intake will be assessed through a targeted dietary questionnaire	Baseline and One Year follow-up