The placebo device is identical in appearance and function to the active platform; except when activated, it emits the same sound as the active device but does not deliver the vibration.

Low magnitude, high frequency mechanical stimulation device ("vibrating") platform

Participants will be randomly assigned to stand on a low magnitude, high frequency mechanical stimulation device ("vibrating") platform for 10 minutes twice daily for one year. The study hypothesizes participants in the intervention arm intervention will demonstrate improved total bone mineral content for height, spinal and tibial bone mineral density and tibial bone strength when compared to those who are randomized to the placebo intervention.

LMHF mechanical stimulation active device

LMHF mechanical stimulation placebo device

Kirsten K Ness, PT, Ph.D

Treatment for childhood cancer interferes with normal bone maturation such that maximal peak bone mass may never be attained by some survivors of childhood cancer. In childhood cancer survivors, a randomized trial evaluating the effectiveness of vitamin D and calcium supplementation among ALL survivors is currently underway; however, few other interventions have been offered for this at risk population. Recent evidence demonstrates that low magnitude; high frequency mechanical stimulation can improve bone quantity and quality, perhaps providing an alternative or adjunct to pharmacologic intervention in populations where additional medications are either contraindicated or not acceptable to the individuals at risk. This application proposes a prospective double blind randomized clinical trial of low magnitude, high frequency mechanical (LMHF) stimulation for childhood cancer survivors whose bone mineral density is one or more standard deviations below the mean for their age and gender.

This study is a two arm parallel allocation of participants to either the intervention or control group will be utilized for a one year trial.

Participants will be randomly assigned to stand on a low magnitude, high frequency mechanical stimulation device ("vibrating") platform for 10 minutes twice daily for one year. Participants in the control arm will stand on a placebo device.

This study will evaluate the effects of low magnitude, high frequency stimulus on bone mineral content(BMC), bone mineral density (BMD), and bone strength in childhood cancer survivors who present with BMD values 1.0 or more standard deviations below the mean for their age and gender for the lumbar or whole body. This study will evaluate the effects of low magnitude, high frequency stimulus on markers of bone turnover in childhood cancer survivors who present with BMD values 1.0 or more standard deviations below the mean for their age and gender for the lumbar or whole body.

At baseline participants will have evaluations to determine bone mineral content and bone mineral density (Dual X-ray Absorptiometry and Qualitative Computed Tomography) and a blood sample collected to measure biomarkers of bone turnover, hormonal status and Vitamin D metabolism. Anthropometrics and tanner stage will be obtained at baseline, 3 months, 6 months, 9 and 12 months. A physical activity monitor will be worn for a 7 day period and a food frequency questionnaire will be completed. Tibial length will be measured. Participants have a blood sample collected either at home or at St. Jude Children's Research Hospital (SJCRH) every 3 months during the study to measure biomarkers of bone turnover, hormonal status and Vitamin D metabolism, anthropometrics and tanner stage, physical activity monitor and food frequency questionnaire. All measurements and evaluations required at baseline will be repeated at the completion of study visit.

Vibration Intervention For Bone Enhancement In Childhood Cancer Survivors

Since this is considered a "pilot study" we did not adjust for multiple comparisons. These % changes were treated as continuous variables and analyzed using two way ANOVAs adjusting for stratification.

Biological markers of bone formation and cytokines collected at baseline and 12 months were evaluated to see if there was change over time.

Biological markers of bone formation and cytokines collected at baseline and 12 months were evaluated to see if there was change over time. BCE = Bone Collagen Equivalent.

Biological markers evaluated are: Osteoprotegerin (OPG)/receptor activator nuclear factor kB ligand (sRANKL) index.

Between-group comparisons used two-sample t-tests. Biomarkers and cytokines collected at baseline and 12 months were evaluated to see if there was change over time. Variables were log transformed for analysis.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Gabrielle's Angel Foundation

St. Jude Children's Research Hospital

Adverse events were reported in real time. The SJCRH IRB requires that study PI's report any unanticipated events involving risk to subjects or others during the conduct of the study. Appropriate action is discussed and the PI is notified to implement the decided action plan.

Low magnitude, high frequency mechanical stimulation device ("vibrating") platform

LMHF mechanical stimulation active device: Participants were randomly assigned to stand on a low magnitude, high frequency mechanical stimulation device ("vibrating") platform for 10 minutes twice daily for one year. The study hypothesized participants randomized to the active device would demonstrate improved total bone mineral content for height, spinal and tibial bone mineral density and tibial bone strength when compared to those who were randomized to the placebo intervention.

LMHF Mechanical Stimulation

The placebo device is identical in appearance and function to the active platform; except when activated, it emits the same sound as the active device but does not deliver the vibration.

Placebo device: Participants were randomly assigned to stand on a placebo device for 10 minutes twice daily for one year. The study hypothesized participants in the intervention arm would demonstrate improved total bone mineral content for height, spinal and tibial bone mineral density and tibial bone strength when compared to those who were randomized to the placebo arm.

Placebo Device

Total

Age, Continuous

Sex: Female, Male

The power estimates were based on two-sided two-sample t-tests. With 30 subjects in each of the two arms and assuming no change in the control arm (0% change) and assuming the common standard deviation (SD) of 6.8%3 we will have roughly 87% power to detect an improvement of 5.5% change in the intervention arm, with type I error control α=0.05.

Dropout was higher than expected leading to small numbers for analysis. It was estimated that 30 persons were needed in each arm to detect a 5.5% difference in change in bone outcomes between the active device and placebo device arms of the study.

Kirsten K. Ness, PT, PhD

The power estimates were based on two-sided two-sample t-tests. With 30 subjects in each of the two arms and assuming no change in the control arm (0% change) and assuming the common standard deviation (SD) of 6.8% we estimated 87% power to detect an improvement of 5.5% change in the intervention arm, with type I error control α=0.05.

Percent Change in Total Bone Mineral Content (BMC) Per Height Compared Between Intervention and Placebo Groups

Active and placebo group means were compared with a 2-sample t-test after log-transforming the variable.

Mean Change in Aminoterminal Propeptide of Type I Procollagen (PINP) Compared Between the Intervention and Placebo Groups

Percent Change in Lumbar Spine Bone Mineral Content (BMC) Compared Between Intervention and Placebo Groups

The power estimates were based on two-sided two-sample t-tests. With 30 subjects in each of the two arms and assuming no change in the control arm (0% change) and assuming the common standard deviation (SD) of 6.8%3 we estimated 87% power to detect an improvement of 5.5% change in the intervention arm, with type I error control α=0.05.

Spots Global Cancer Trial Database for lmhf mechanical stimulation placebo device