Crohn Disease
Conditions
Brief summary
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
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.
Interventions
DEVICELow magnitude mechanical stimulus
10 minute daily treatment sessions standing on the low magnitude mechanical stimulus device
DEVICEPlacebo (inactive) low magnitude mechanical stimulus
10 minute daily treatments standing on a placebo version of a low magnitude mechanical stimulus device
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Children's Hospital of Philadelphia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 21 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Tibia Trabecular Volumetric Bone Mineral Density (BMD) Z-score at 12 Months | 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. |
| Change in Tibia Cortical Area Z-score 12 Months | 12 months | We calculated the mean change in tibia cortical area Z-score, as measured by pQCT, between baseline and 12 months. |
| Change in Spine Volumetric BMD Z-score at 12 Months | 12 months | We calculated the mean change in spine volumetric BMD Z-score, as measured by QCT, between baseline and 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Whole Body Bone Mineral Content Z-score Between Baseline and 12 Months | 12 months | We calculated the mean change in whole body bone mineral content Z-score, as measured by DXA, between baseline and 12 months |
| Change in Posteroanterior Lumbar Spine Areal BMD Z-score | 12 months | We calculated the mean change in posterior anterior lumbar spine areal BMD Z-score between baseline and 12 months as measured by DXA |
| Change in QCT Tibia Trabecular Volumetric BMD at 12 Months | 12 months | We calculated the mean change in tibia trabecular volumetric BMDbetween baseline and 12 months as measured by (QCT) |
| Change in Total Hip Areal BMD Z-score Between Baseline and 12 Months | 12months | We calculated the mean change in total hip bone mineral density z-score, as measured by DXA, between baseline and 12 months |
| Change in Femoral Neck Areal BMD Z-score Between Baseline and 12 Months | 12 months | We calculated the mean change in femoral neck areal bmd Z-score between baseline and 12 months as measured by DXA |
Countries
United States
Participant flow
Recruitment details
The recruitment period began May 17, 2007 and ended June 25, 2010. Participants were recruited from the Center for Inflammatory Bowel Disease at CHOP and through referrals from physicians outside CHOP. The study was also advertised on the Crohn's and Colitis Foundation Website.
Pre-assignment details
Patients between the ages of 8-21 years with a diagnosis of Crohn disease for at least 6 months were eligible for a screening visit. Patients meeting the entry criteria (pQCT trabecular volumetric BMD z-score below the 25th percentile)were randomly allocated 1:1 to an active LMMS device or a placebo device.
Participants by arm
| Arm | Count |
|---|---|
| Active Active Low Magnitude Mechanical Stimulus
Low magnitude mechanical stimulus : 10 minute daily treatment sessions standing on the low magnitude mechanical stimulus device | 69 |
| Pacebo Placebo (inactive) low magnitude mechanical stimulus : 10 minute daily treatments standing on a placebo version of a low magnitude mechanical stimulus device | 69 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Intervention Period | Lost to Follow-up | 4 | 3 |
| Intervention Period | Pregnancy | 1 | 0 |
| Intervention Period | Withdrawal by Subject | 4 | 5 |
| Post Intervention Follow-up Period | Lost to Follow-up | 5 | 11 |
Baseline characteristics
| Characteristic | Pacebo | Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 63 Participants | 63 Participants | 126 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Continuous | 14.51452 years STANDARD_DEVIATION 2.720447 | 14.11475 years STANDARD_DEVIATION 2.900821 | 14.3134 years STANDARD_DEVIATION 2.816848 |
| Region of Enrollment United States | 69 participants | 69 participants | 138 participants |
| Sex: Female, Male Female | 33 Participants | 33 Participants | 66 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 69 | 10 / 69 |
| serious Total, serious adverse events | 7 / 69 | 6 / 69 |
Outcome results
Primary
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
Time frame: 12 months
Population: The number was determined by the number of participants with measures at both baseline and 12 month time points. The analysis was intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Spine Volumetric BMD Z-score at 12 Months | 0.22 Z-score | Standard Deviation 0.59 |
| Pacebo | Change in Spine Volumetric BMD Z-score at 12 Months | -0.02 Z-score | Standard Deviation 0.67 |
p-value: 0.02Regression, Linear
Primary
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.
Time frame: 12 months
Population: The number was determined by the number of participants with measures at both baseline and 12 month time points. The analysis was intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Tibia Cortical Area Z-score 12 Months | 0.17 Z-score | Standard Deviation 0.58 |
| Pacebo | Change in Tibia Cortical Area Z-score 12 Months | 0.20 Z-score | Standard Deviation 0.59 |
p-value: 0.8Regression, Linear
Primary
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.
Time frame: 12 months
Population: The number was determined by the number of participants with measures at both baseline and 12 month time points. The analysis was intention to treat.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Tibia Trabecular Volumetric Bone Mineral Density (BMD) Z-score at 12 Months | 0.15 Z-score | Standard Deviation 0.55 |
| Pacebo | Change in Tibia Trabecular Volumetric Bone Mineral Density (BMD) Z-score at 12 Months | 0.23 Z-score | Standard Deviation 0.7 |
p-value: 0.38Regression, Linear
Secondary
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
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Femoral Neck Areal BMD Z-score Between Baseline and 12 Months | 0.19 Z-score | Standard Deviation 0.45 |
| Pacebo | Change in Femoral Neck Areal BMD Z-score Between Baseline and 12 Months | 0.22 Z-score | Standard Deviation 0.45 |
p-value: 0.66Regression, Linear
Secondary
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
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Posteroanterior Lumbar Spine Areal BMD Z-score | 0.20 Z-score | Standard Deviation 0.44 |
| Pacebo | Change in Posteroanterior Lumbar Spine Areal BMD Z-score | 0.09 Z-score | Standard Deviation 0.44 |
p-value: 0.27Regression, Linear
Secondary
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)
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in QCT Tibia Trabecular Volumetric BMD at 12 Months | 1.05 cm^3 | Standard Deviation 10.5 |
| Pacebo | Change in QCT Tibia Trabecular Volumetric BMD at 12 Months | 1.35 cm^3 | Standard Deviation 12.93 |
p-value: 0.98Regression, Linear
Secondary
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
Time frame: 12months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Total Hip Areal BMD Z-score Between Baseline and 12 Months | 0.24 Z-score | Standard Deviation 0.44 |
| Pacebo | Change in Total Hip Areal BMD Z-score Between Baseline and 12 Months | 0.25 Z-score | Standard Deviation 0.43 |
p-value: 0.84Regression, Linear
Secondary
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
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change in Whole Body Bone Mineral Content Z-score Between Baseline and 12 Months | 0.20 Z-score | Standard Deviation 0.4 |
| Pacebo | Change in Whole Body Bone Mineral Content Z-score Between Baseline and 12 Months | 0.18 Z-score | Standard Deviation 0.43 |
p-value: 0.7Regression, Linear