Effect of Botox and Vibration on Bone in Children With Cerebral Palsy

NCT ID: NCT01803464

Last Updated: 2018-03-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2015-02-28

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).

Conditions

Cerebral Palsy; Muscle Spasticity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Botox plus low-magnitude vibration

Cerebral palsy and Botox + vibration

Group Type: EXPERIMENTAL

Low-magnitude vibration

Intervention Type: DEVICE

Children will receive a daily low-magnitude vibration treatment.

Botox

Intervention Type: DRUG

Children who are candidates to receive Botox as part of their standard of care.

Botox

Cerebral palsy and Botox

Group Type: EXPERIMENTAL

Botox

Intervention Type: DRUG

Children who are candidates to receive Botox as part of their standard of care.

Cerebral palsy control

Cerebral palsy without treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Typically developing control

Typically developing

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Low-magnitude vibration

Children will receive a daily low-magnitude vibration treatment.

Intervention Type: DEVICE

Botox

Children who are candidates to receive Botox as part of their standard of care.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alfred I. duPont Hospital for Children

OTHER

Sponsor Role: collaborator

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

NIH

Sponsor Role: collaborator

University of Delaware

OTHER

Sponsor Role: lead

Responsible Party

Christopher Modlesky

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Christopher Modlesky, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Delaware

Freeman Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Nemours/Alfred I duPont Hospital for Children

Locations

University of Delaware

Newark, Delaware, United States

Alfred I. duPont Hospital for Children, Nemours

Wilmington, Delaware, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 19111321 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17962918 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11811566 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12572652 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20864862 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15040823 (View on PubMed)

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.

Reference Type: RESULT

PMID: 25199575 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24269277 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26392035 (View on PubMed)

Other Identifiers

IRB # 115648-11

Identifier Type: OTHER

Identifier Source: secondary_id

1R15HD071397-01

Identifier Type: NIH

Identifier Source: secondary_id

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1R15HD071397-01

Identifier Type: NIH

Identifier Source: org_study_id

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