Bone Health in Pediatric Crohn's Disease: A Low Magnitude Mechanical Stimulus Trial

Study Overview
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Brief Summary
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The purpose of this 12-month double blind, placebo controlled randomized trial is to evaluate the effects of daily treatments with low magnitude mechanical stimuli on bone in 160 children with Crohn disease.

Detailed Description
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Skeletal growth is characterized by increases in the size of the hard outer layer of bone (cortical bone), and the density of the inner layer of bone (trabecular or spongy bone). Children with Crohn disease (CD) have numerous risk factors for impaired bone accumulation, including poor growth, delayed puberty, malnutrition, glucocorticoid therapy and inflammation. We reported that children with CD had significant deficits in trabecular bone mineral density (BMD), cortical dimensions, and muscle mass; bone deficits were strongly associated with muscle deficits. No trials of therapies that build bone or prevent bone breakdown have been conducted in chronic pediatric inflammatory diseases. The capacity to increase bone mass and dimensions in response to mechanical loading is greatest during growth. Recent studies demonstrate that brief daily exposure to low magnitude mechanical stimuli (LMMS) enhances bone mass and quality. This 12-month double blind, placebo controlled randomized trial will evaluate daily 10-minute treatments with LMMS in 160 children with CD. Trabecular BMD, cortical dimensions, and muscle area will be measured by quantitative computed tomography (QCT). The LMMS device monitors adherence; these data will be transmitted by modem to the psychologist who will work closely with subjects to optimize adherence. All subjects will be provided with calcium and vitamin D supplements. The primary aims are to determine if treatment with LMMS results in increased trabecular BMD in the lower leg and spine and increased cortical dimensions in the lower leg in children with CD, compared with placebo controls.

Official Title
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Bone Health in Pediatric Crohn's Disease: A Low Magnitude Mechanical Stimulus Trial

Conditions
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Crohn Disease

Intervention / Treatment
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* Device: Low magnitude mechanical stimulus
* Device: Placebo (inactive) low magnitude mechanical stimulus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 8-21 years Diagnosis of Crohn disease > 6 months Tibia vBMD z-score < 25th%tile for age and sex Exclusion Criteria: Pregnancy Weight > 250 lb Medical illness (unrelated to Crohn) Cognitive/developmental disorder Do not speak English > 1 primary residence Unwilling to commit to 2 year study Sibling or cousin enrolled in trial

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Low Magnitude Mechanical Stimulus<br>Active Low Magnitude Mechanical Stimulus | Device: Low magnitude mechanical stimulus<br>* 10 minute daily treatment sessions standing on the low magnitude mechanical stimulus device<br>* Other names: Whole body vibration;|
| Placebo Comparator: Inactive Low Magnitude mechanical Stimulus<br>Inactive, or placebo low magnitude mechanical stimulus | Device: Placebo (inactive) low magnitude mechanical stimulus<br>* 10 minute daily treatments standing on a placebo version of a low magnitude mechanical stimulus device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tibia Trabecular Volumetric Bone Mineral Density (BMD) Z-score at 12 Months | We calculated the mean change in tibia trabecular volumetric BMD Z-score between baseline and 12 months, as measured by peripheral quantitative computed tomography (pQCT). The Z-score, or Standard Deviation Score, is a measure of the number of standard deviations that an individual is above or below the median value in a healthy child or adolescent of the same age, sex and race. For example, a Z-score of 0 means that an individual's result is equivalent to the 50th percentile in a healthy population. A Z-score of -1.0 means that an individual's result is equovalent to the 16th percentile in a healthy population. | 12 months | 
| Change in Tibia Cortical Area Z-score 12 Months | We calculated the mean change in tibia cortical area Z-score, as measured by pQCT, between baseline and 12 months. | 12 months | 
| Change in Spine Volumetric BMD Z-score at 12 Months | We calculated the mean change in spine volumetric BMD Z-score, as measured by QCT, between baseline and 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Posteroanterior Lumbar Spine Areal BMD Z-score | We calculated the mean change in posterior anterior lumbar spine areal BMD Z-score between baseline and 12 months as measured by DXA | 12 months | 
| Change in Total Hip Areal BMD Z-score Between Baseline and 12 Months | We calculated the mean change in total hip bone mineral density z-score, as measured by DXA, between baseline and 12 months | 12months | 
| Change in Femoral Neck Areal BMD Z-score Between Baseline and 12 Months | We calculated the mean change in femoral neck areal bmd Z-score between baseline and 12 months as measured by DXA | 12 months | 
| Change in Whole Body Bone Mineral Content Z-score Between Baseline and 12 Months | We calculated the mean change in whole body bone mineral content Z-score, as measured by DXA, between baseline and 12 months | 12 months | 
| Change in QCT Tibia Trabecular Volumetric BMD at 12 Months | We calculated the mean change in tibia trabecular volumetric BMDbetween baseline and 12 months as measured by (QCT) | 12 months |