Cerebral Palsy, Muscle Spasticity
Conditions
Keywords
Botox, Muscle strength
Brief summary
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.
Detailed description
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).
Interventions
DEVICELow-magnitude vibration
Children will receive a daily low-magnitude vibration treatment.
DRUGBotox
Children who are candidates to receive Botox as part of their standard of care.
Sponsors
Alfred I. duPont Hospital for Children
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Delaware
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
Yes
Inclusion criteria
Inclusion (Children with CP): 1. Have spastic CP 2. Between 2-12 years of age 3. Recommended for Botox treatment by their physician as part of their clinical care. Those who accept Botox treatment and those who do not accept Botox treatment are both eligible for the study. 4. A score of 1-4 on the gross motor function classification scale (GMFCS) Exclusion (Children with CP): 1. Botox treatment in the lower extremities within the last year 2. Metal rods in both legs Inclusion (Typically developing children): 1. Between 2 and 12 years of age. 2. Match a child with CP for sex, age and race. Exclusion(Typically developing children): 1. Neurological disorder 2. Surgery in the lower extremities within the last year. 3. Chronic medication use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Structure | baseline to 6 months | Change in cortical bone volume of the middle third of the tibia from baseline to 6 months, as measured by MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Volume | baseline to 6 months | Change in muscle volume of the midleg from baseline to 6 months, as measured by MRI |
| Bone Mass | baseline to 6 months | Change in bone mineral content in the distal femur from baseline to 6 months, as measured by dual-energy X-ray absorptiometry (DXA) |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 5 |
| 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. | 4 |
| Cerebral Palsy Control Children with cerebral palsy who are recommended for but decline Botox treatment will serve as controls. | 10 |
| Typically Developing Control Typically developing children without cerebral palsy will serve as controls. | 10 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Incomplete data | 0 | 0 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Botox Plus Low-magnitude Vibration | Botox | Cerebral Palsy Control | Typically Developing Control | Total |
|---|---|---|---|---|---|
| Age, Continuous | 7.73 years STANDARD_DEVIATION 2.85 | 8.50 years STANDARD_DEVIATION 2.65 | 7.61 years STANDARD_DEVIATION 2.22 | 8.71 years STANDARD_DEVIATION 1.68 | 8.13 years STANDARD_DEVIATION 2.16 |
| Region of Enrollment United States | 5 participants | 4 participants | 10 participants | 10 participants | 29 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 4 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 6 Participants | 7 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 5 | 0 / 4 | 0 / 10 | 3 / 10 |
| serious Total, serious adverse events | 0 / 5 | 0 / 4 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Bone Structure
Change in cortical bone volume of the middle third of the tibia from baseline to 6 months, as measured by MRI.
Time frame: baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Plus Low-magnitude Vibration | Bone Structure | 10.4 percent change | Standard Deviation 8.6 |
| Botox | Bone Structure | 7.6 percent change | Standard Deviation 10.2 |
| Cerebral Palsy Control | Bone Structure | 6.7 percent change | Standard Deviation 4.7 |
| Typically Developing Control | Bone Structure | 9.0 percent change | Standard Deviation 4.4 |
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)
Time frame: baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Plus Low-magnitude Vibration | Bone Mass | 8.1 percent change | Standard Deviation 4.3 |
| Botox | Bone Mass | 3.2 percent change | Standard Deviation 3.9 |
| Cerebral Palsy Control | Bone Mass | 4.2 percent change | Standard Deviation 2.5 |
| Typically Developing Control | Bone Mass | 3.1 percent change | Standard Deviation 3.9 |
Secondary
Muscle Volume
Change in muscle volume of the midleg from baseline to 6 months, as measured by MRI
Time frame: baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botox Plus Low-magnitude Vibration | Muscle Volume | 9.5 percent change | Standard Deviation 13.5 |
| Botox | Muscle Volume | 10.9 percent change | Standard Deviation 14.2 |
| Cerebral Palsy Control | Muscle Volume | 5.1 percent change | Standard Deviation 7.4 |
| Typically Developing Control | Muscle Volume | 3.9 percent change | Standard Deviation 10.1 |