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| ID | Type | Description | Link |
|---|---|---|---|
| IRB # 115648-11 | Other Identifier | Alfred I. duPont Hospital for the Children | |
| 1R15HD071397-01 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Alfred I. duPont Hospital for Children | OTHER |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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Cerebral palsy (CP) is a neuromuscular disorder that affects approximately 800,000 individuals in the U.S. An estimated 70-80% of these individuals have spasticity which affects ambulation and requires management. Therefore, the treatment of spasticity is a primary goal of interventions for children with CP. One treatment widely used to reduce spasticity is Botox because of its ability to temporarily paralyze a muscle. However, no studies have determined the effect of Botox treatment on bone in humans. Also, a low magnitude vibration treatment has been shown to improve bone structure in the lower extremity bones of children with CP. The aims of this study are: 1) to determine the effect of Botox treatment in conjunction with a daily vibration treatment on bone mass and bone structure in children with spastic CP, and 2) to identify the mechanism that underlies the effect of Botox and vibration on bone.
The investigators have been working with children diagnosed with cerebral palsy (CP) for the past 10 years. The investigators have found that bone structure is markedly underdeveloped and bone strength is severely compromised in children with CP. Also, an increased fracture rate has been observed in the lower extremity bones of children with CP. There is evidence that Botox, which is used to treat spasticity in CP, can improve motor function; however the effect of Botox on human bone is unknown. There is also evidence that low magnitude vibration treatment can improve bone mass and bone structure. The overall goal of this current research study is to investigate the effect and mechanism of action of Botox and vibration on bone in children with CP. The investigators will also examine the effect of Botox on muscle volume.
A total of 36 participants will participate in this study. The investigators will assess bone structure and muscle volume using MRI. The investigators will assess bone mass using dual-energy X-ray absorptiometry (DXA).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Botox plus low-magnitude vibration | Experimental | Cerebral palsy and Botox + vibration |
|
| Botox | Experimental | Cerebral palsy and Botox |
|
| Cerebral palsy control | No Intervention | Cerebral palsy without treatment | |
| Typically developing control | No Intervention | Typically developing |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low-magnitude vibration | Device | Children will receive a daily low-magnitude vibration treatment. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Bone Structure | Change in cortical bone volume of the middle third of the tibia from baseline to 6 months, as measured by MRI. | baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Muscle Volume | Change in muscle volume of the midleg from baseline to 6 months, as measured by MRI | baseline to 6 months |
| Bone Mass | Change in bone mineral content in the distal femur from baseline to 6 months, as measured by dual-energy X-ray absorptiometry (DXA) |
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Inclusion (Children with CP):
Exclusion (Children with CP):
Inclusion (Typically developing children):
Exclusion(Typically developing children):
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Modlesky, PhD | University of Delaware | Principal Investigator |
| Freeman Miller, MD | Nemours/Alfred I duPont Hospital for Children | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Delaware | Newark | Delaware | 19716 | United States | ||
| Alfred I. duPont Hospital for Children, Nemours |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19111321 | Background | Johnson DL, Miller F, Subramanian P, Modlesky CM. Adipose tissue infiltration of skeletal muscle in children with cerebral palsy. J Pediatr. 2009 May;154(5):715-20. doi: 10.1016/j.jpeds.2008.10.046. Epub 2008 Dec 25. | |
| 17962918 | Background | Modlesky CM, Subramanian P, Miller F. Underdeveloped trabecular bone microarchitecture is detected in children with cerebral palsy using high-resolution magnetic resonance imaging. Osteoporos Int. 2008 Feb;19(2):169-76. doi: 10.1007/s00198-007-0433-x. Epub 2007 Oct 26. |
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De-identified individual participant data for all primary and secondary outcome measures will be made available.
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Within 30 days of the request.
Data access requests will be reviewed by the PIs. Requestors will be required to sign a Data Access Agreement.
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62 children with spastic cerebral palsy eligible for botulinum toxin treatment and typically developing children were screened. 5 children did not meet the study criteria and 57 children were invited to participate in the study, of which 29 participated in the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Botox Plus Low-magnitude Vibration | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to also receive vibration treatment. Children will be asked to stand on a vibration plate 10 minutes per day for 6 months. Botox plus low-magnitude vibration: Half of the children who receive Botox treatment will be randomly assigned to receive a high-frequency, low magnitude vibration treatment. The other half of the children who receive Botox treatment and are randomly assigned to the Botox-only group will be offered the vibration treatment at the end of the study. |
| FG001 | Botox | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to serve as a Botox-only group. Botox: Children will not receive vibration treatment. Children in the Botox-only group will be offered vibration treatment at the end of the study. |
| FG002 | Cerebral Palsy Control | Children with cerebral palsy who are recommended for but decline Botox treatment will serve as controls. |
| FG003 | Typically Developing Control | Typically developing children without cerebral palsy will serve as controls. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Botox Plus Low-magnitude Vibration | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to also receive vibration treatment. Children will be asked to stand on a vibration plate 10 minutes per day for 6 months. Botox plus low-magnitude vibration: Half of the children who receive Botox treatment will be randomly assigned to receive a high-frequency, low magnitude vibration treatment. The other half of the children who receive Botox treatment and are randomly assigned to the Botox-only group will be offered the vibration treatment at the end of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Bone Structure | Change in cortical bone volume of the middle third of the tibia from baseline to 6 months, as measured by MRI. | Posted | Mean | Standard Deviation | percent change | baseline to 6 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Botox Plus Low-magnitude Vibration | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to also receive vibration treatment. Children will be asked to stand on a vibration plate 10 minutes per day for 6 months. Botox plus low-magnitude vibration: Half of the children who receive Botox treatment will be randomly assigned to receive a high-frequency, low magnitude vibration treatment. The other half of the children who receive Botox treatment and are randomly assigned to the Botox-only group will be offered the vibration treatment at the end of the study. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment | Participants became nauseous while standing on the vibration platform during a 10 minute session. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christopher Modlesky | University of Delaware | 302-831-4185 | modlesky@udel.edu |
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| ID | Term |
|---|---|
| D002547 | Cerebral Palsy |
| D009128 | Muscle Spasticity |
| ID | Term |
|---|---|
| D001925 | Brain Damage, Chronic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
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| Botox | Drug | Children who are candidates to receive Botox as part of their standard of care. |
|
| baseline to 6 months |
| Wilmington |
| Delaware |
| 19899 |
| United States |
| 11811566 | Background | Rubin C, Turner AS, Muller R, Mittra E, McLeod K, Lin W, Qin YX. Quantity and quality of trabecular bone in the femur are enhanced by a strongly anabolic, noninvasive mechanical intervention. J Bone Miner Res. 2002 Feb;17(2):349-57. doi: 10.1359/jbmr.2002.17.2.349. |
| 12572652 | Background | Judex S, Boyd S, Qin YX, Turner S, Ye K, Muller R, Rubin C. Adaptations of trabecular bone to low magnitude vibrations result in more uniform stress and strain under load. Ann Biomed Eng. 2003 Jan;31(1):12-20. doi: 10.1114/1.1535414. |
| 20864862 | Background | Wren TA, Lee DC, Hara R, Rethlefsen SA, Kay RM, Dorey FJ, Gilsanz V. Effect of high-frequency, low-magnitude vibration on bone and muscle in children with cerebral palsy. J Pediatr Orthop. 2010 Oct-Nov;30(7):732-8. doi: 10.1097/BPO.0b013e3181efbabc. |
| 15040823 | Background | Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Miner Res. 2004 Mar;19(3):360-9. doi: 10.1359/JBMR.040129. Epub 2004 Jan 27. |
| 25199575 | Result | Modlesky CM, Whitney DG, Singh H, Barbe MF, Kirby JT, Miller F. Underdevelopment of trabecular bone microarchitecture in the distal femur of nonambulatory children with cerebral palsy becomes more pronounced with distance from the growth plate. Osteoporos Int. 2015 Feb;26(2):505-12. doi: 10.1007/s00198-014-2873-4. Epub 2014 Sep 9. |
| 24269277 | Result | Modlesky CM, Whitney DG, Carter PT, Allerton BM, Kirby JT, Miller F. The pattern of trabecular bone microarchitecture in the distal femur of typically developing children and its effect on processing of magnetic resonance images. Bone. 2014 Mar;60:1-7. doi: 10.1016/j.bone.2013.11.009. Epub 2013 Nov 20. |
| 26392035 | Derived | Singh H, Whitney DG, Knight CA, Miller F, Manal K, Kolm P, Modlesky CM. Site-Specific Transmission of a Floor-Based, High-Frequency, Low-Magnitude Vibration Stimulus in Children With Spastic Cerebral Palsy. Arch Phys Med Rehabil. 2016 Feb;97(2):218-23. doi: 10.1016/j.apmr.2015.08.434. Epub 2015 Sep 21. |
| Withdrawal by Subject |
|
| BG001 | Botox | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to serve as a Botox-only group. Botox: Children will not receive vibration treatment. Children in the Botox-only group will be offered vibration treatment at the end of the study. |
| BG002 | Cerebral Palsy Control | Children with cerebral palsy who are recommended for but decline Botox treatment will serve as controls. |
| BG003 | Typically Developing Control | Typically developing children without cerebral palsy will serve as controls. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Botox |
Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to serve as a Botox-only group. Botox: Children will not receive vibration treatment. Children in the Botox-only group will be offered vibration treatment at the end of the study. |
| OG002 | Cerebral Palsy Control | Children with cerebral palsy who are recommended for but decline Botox treatment will serve as controls. |
| OG003 | Typically Developing Control | Typically developing children without cerebral palsy will serve as controls. |
|
|
|
| Secondary | Muscle Volume | Change in muscle volume of the midleg from baseline to 6 months, as measured by MRI | Posted | Mean | Standard Deviation | percent change | baseline to 6 months |
|
|
|
|
| Secondary | Bone Mass | Change in bone mineral content in the distal femur from baseline to 6 months, as measured by dual-energy X-ray absorptiometry (DXA) | Posted | Mean | Standard Deviation | percent change | baseline to 6 months |
|
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| EG001 | Botox | Children with cerebral palsy who are recommended for and scheduled to receive Botox treatment will randomized to serve as a Botox-only group. Botox: Children will not receive vibration treatment. Children in the Botox-only group will be offered vibration treatment at the end of the study. | 0 | 4 | 0 | 4 |
| EG002 | Cerebral Palsy Control | Children with cerebral palsy who are recommended for but decline Botox treatment will serve as controls. | 0 | 10 | 0 | 10 |
| EG003 | Typically Developing Control | Typically developing children without cerebral palsy will serve as controls. | 0 | 10 | 3 | 10 |
|
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| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009122 | Muscle Hypertonia |
| D020879 | Neuromuscular Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| Cohen's d |
| 0.57 |
| 2-Sided |
Cohen's d was calculated. The % change of the Botox group minus the % change of the cerebral palsy control group was the numerator. The pooled SD of the % change for the 2 groups was the denominator. |
| Other |
| Cohen's d | 0.13 | 2-Sided | Cohen's d was calculated. The % change of the typically developing group minus the % change of the cerebral palsy control group was the numerator. The pooled SD of the % change for the 2 groups was the denominator | Other |
| Cohen's d |
| 0.33 |
| 2-Sided |
Cohen's d was calculated. The % change of the Botox group minus the % change of the cerebral palsy control group was the numerator. The pooled SD of the % change for the 2 groups was the denominator. |
| Other |
| Cohen's d | 0.33 | 2-Sided | Cohen's d was calculated. The % change of the typically developing control group minus the % change of the cerebral palsy control group was the numerator. The pooled SD of the % change for the 2 groups was the denominator. | Other |