Clinical trial NCT04508088: Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease
Official title: Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescents With Crohn Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Inflammatory Bowel Disease
Crohn Disease
Keywords: Crohn
Bone Marrow
Dual-energy X-ray absorptiometry
Peripheral Quantitative Computed Tomography
Magnetic Resonance Imaging
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
First posted: 2020-08-11
Enrollment: 92
Sex: ALL
Minimum age (years): 13
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Bone marrow adiposity by magnetic resonance imaging (MRI)
timeFrame: Baseline and One Year follow-up
measure: Magnetic resonance spectroscopy (MRS)
timeFrame: Baseline and One Year follow-up
Secondary outcomes:
measure: Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA)
timeFrame: Baseline and One Year follow-up
measure: Spine BMD Z-score by DXA
timeFrame: Baseline and One Year follow-up
measure: Spine apparent density Z-score by DXA
timeFrame: Baseline and One Year follow-up
measure: Volumetric bone mineral density (vBMD)
timeFrame: Baseline and One Year follow-up
measure: Bone strength by quantitative computed tomography pQCT
timeFrame: Baseline and One Year follow-up
measure: Bone Formation Marker #1
timeFrame: Baseline and One Year follow-up
measure: Bone Formation Marker #2
timeFrame: Baseline and One Year follow-up
measure: Bone Resorption Marker
timeFrame: Baseline and One Year follow-up
measure: Immune Studies
timeFrame: Baseline and One Year follow-up
measure: Current Crohn's Disease Activity
timeFrame: Baseline and One Year follow-up
measure: Physical Activity
timeFrame: Baseline and One Year follow-up
measure: Dietary Calcium Intake
timeFrame: Baseline and One Year follow-up
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Rebecca Gordon, MD
role: PRINCIPAL_INVESTIGATOR
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