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

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ClinicalTrials.gov Identifier: NCT04508088
Recruitment Status : Recruiting
First Posted : August 11, 2020
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
Rebecca Gordon, Boston Children's Hospital

Brief Summary:
The investigators will be evaluating bone marrow composition via magnetic resonance imaging in newly diagnosed adolescent girls with Crohn disease 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. In this pilot study, data will be collected via chart review and novel imaging evaluation.

Condition or disease Intervention/treatment
Inflammatory Bowel Disease Crohn Disease Diagnostic Test: Coronal T1 weighted spin echo images Diagnostic Test: Spin-lattice relaxation (T1) Diagnostic Test: Magnetic resonance spectroscopy

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 pilot study aims to focus on abnormalities in bone marrow, and specifically whether adolescent girls 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 lesser bone formation and worse bone health. The central objective is to obtain pilot data on the differences in bone marrow between healthy adolescent girls and those with CD. Long term, the investigators want to study how abnormal fat tissue and sub-optimal bone health relate to each other.

The study involves 10 adolescent females recently diagnosed with CD and 10 healthy females. 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 females will be matched with healthy females based on age, stage of puberty, height percentile, 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.

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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Skeletal Health and Bone Marrow Composition in Newly Diagnosed Adolescent Girls With Crohn Disease
Actual Study Start Date : September 10, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Crohn's Disease

Group/Cohort Intervention/treatment
Crohn Disease

This group will be 10 adolescent girls, ages 13-20, who have been recently (within 12 months) diagnosed with Crohn Disease.

All participants will have a single study visit 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.

Control

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

All participants will have a single study visit 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.




Primary Outcome Measures :
  1. Bone marrow adiposity by magnetic resonance imaging (MRI) [ Time Frame: Baseline ]
    Bone marrow adiposity measured by MRI (T1 maps)

  2. Magnetic resonance spectroscopy (MRS) [ Time Frame: Baseline ]
    T2 corrected fat/(fat+ water) ratios


Secondary Outcome Measures :
  1. Total body bone mineral density Z-score by Dual-energy X-ray absorptiometry (DXA) [ Time Frame: Baseline ]
    Total body BMD Z-score

  2. Spine BMD Z-score by DXA [ Time Frame: Baseline ]
    Lumbar spine BMD Z-score

  3. Spine apparent density Z-score by DXA [ Time Frame: Baseline ]
    Lumbar spine bone mineral apparent density (g/cm3)

  4. Volumetric bone mineral density (vBMD) [ Time Frame: Baseline ]
    Quantitative computed tomography (pQCT) scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate

  5. Bone strength by quantitative computed tomography pQCT [ Time Frame: Baseline ]
    PQCT scans will be obtained at sites 3%, 38%, and 66% of tibial length proximal to the distal growth plate

  6. Current Crohn's Disease Activity [ Time Frame: Baseline ]
    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.

  7. Physical Activity [ Time Frame: Baseline ]
    Physical activity will be assessed through a physical activity questionnaire

  8. Dietary Calcium Intake [ Time Frame: Baseline ]
    Dietary calcium intake will be assessed through a targeted dietary questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

The experimental group will be adolescent females aged 13-20 with newly diagnosed CD (within 12 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 both height percentile 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.

Criteria

Inclusion Criteria:

  • Crohn's Disease diagnosed within the past 12 months, or a healthy, matched control
  • height between 5-95%
  • body mass index (BMI) between 5-95%

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04508088


Contacts
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Contact: Rebecca Gordon, MD (617) 355-7476 rebecca.gordon@childrens.harvard.edu

Locations
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United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Rebecca Gordon, MD         
Sponsors and Collaborators
Boston Children's Hospital
Investigators
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Principal Investigator: Rebecca Gordon, MD Boston Children's Hospital
Publications:

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Responsible Party: Rebecca Gordon, Rebecca Gordon, MD Attending Physician, Division of Endocrinology Instructor of Pediatrics, Harvard Medical School, Boston Children's Hospital
ClinicalTrials.gov Identifier: NCT04508088    
Other Study ID Numbers: IRB-P00034878
First Posted: August 11, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Rebecca Gordon, Boston Children's Hospital:
Crohn
Bone Marrow
Dual-energy X-ray absorptiometry
Peripheral Quantitative Computed Tomography
Magnetic Resonance Imaging
Additional relevant MeSH terms:
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Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases