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

NCT01803464 | Completed Results DMC

• 2 other identifiers: 1R15HD071397-01IRB # 115648-11
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Cerebral Palsy; Muscle Spasticity

Keywords

Botox; Muscle strength

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Muscle Volume

  baseline to 6 months

• Bone Mass

  baseline to 6 months

Study Arms (4)

Botox plus low-magnitude vibration

EXPERIMENTAL

Cerebral palsy and Botox + vibration

Device: Low-magnitude vibration; Drug: Botox

Botox

EXPERIMENTAL

Cerebral palsy and Botox

Drug: Botox

Cerebral palsy control

NO INTERVENTION

Cerebral palsy without treatment

Typically developing control

NO INTERVENTION

Typically developing

Interventions

Low-magnitude vibration DEVICE

Children will receive a daily low-magnitude vibration treatment.

Botox plus low-magnitude vibration

Botox DRUG

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

Botox; Botox plus low-magnitude vibration

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Delaware: lead
• Alfred I. duPont Hospital for Children: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

University of Delaware

Newark, Delaware, 19716, United States

Location

Alfred I. duPont Hospital for Children, Nemours

Wilmington, Delaware, 19899, United States

Location

Related Publications (9)

• 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.

  PMID: 19111321 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.

  PMID: 17962918 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.

  PMID: 11811566 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.

  PMID: 12572652 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.

  PMID: 20864862 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.

  PMID: 15040823 BACKGROUND

• 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.

  PMID: 25199575 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.

  PMID: 24269277 RESULT

• 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.

  PMID: 26392035 DERIVED

MeSH Terms

Conditions

Cerebral Palsy; Muscle Spasticity

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Dr. Christopher Modlesky
• Organization: University of Delaware

modlesky@udel.edu

302-831-4185

Study Officials

• Christopher Modlesky, PhD

  University of Delaware

  PRINCIPAL INVESTIGATOR

• Freeman Miller, MD

  Nemours/Alfred I duPont Hospital for Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 4, 2013
• Study Start: March 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 20, 2018
• Results First Posted: March 20, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 30 days of the request.
• Access Criteria: Data access requests will be reviewed by the PIs. Requestors will be required to sign a Data Access Agreement.

Locations

US (2)