Smart AFO and 5-Azacitidine to Enhance Mobility in Children With Cerebral Palsy

The goal of this project is to investigate the impact of the Biomotum Ambulo ankle-foot orthosis on gait outcomes in children with Cerebral Palsy. The device will be tested for its orthotic benefits when providing mechanical ankle assistance and its therapeutic benefits when providing progressive, resistance-based ankle exercise. Through a 1:1 randomization, a subset of opt-in participants will also receive a dose of 5-azacitidine (AZA), an FDA-approved drug for pediatric oncology, or a placebo. Research in muscle fibers has shown that AZA aids in muscle growth and regeneration. The use of AZA in this study is an off-label application employed together with the smart AFO intervention to investigate the impact of targeting both muscular and mechanical deficits related to CP. This project will also collect blood samples of participants to investigate the potential genetic and epigenetic correlations with the severity and trajectory of musculoskeletal impairments and with responses to the smart AFO and AZA interventions.

Inclusion criteria

• Diagnosis of cerebral palsy classified as Gross Motor Function Classification System (GMFCS) levels I to III
• Between 8 and 17 years and 8 months of age at the time of enrollment/consent. Participants that will turn 18 during the course of the study will not be included as pausing the at-home protocol until re-consenting is possible could interfere with intervention results.
• Stable medical condition as determined by the investigator.
• Adequate caregiver support to be able to participate in training and assessment sessions for the duration of the study, at the discretion of the PI.
• Height/weight/BMI between the 5th - 95th percentile of children with cerebral palsy
• Able to walk for at least 6 minutes (assisted or unassisted)
• Able to understand and follow simple directions
• Able to safely fit into a device configuration and tolerate assistance without knee hyperextension while walking
• At least 20 degrees of passive ankle plantar flexion range of motion
• Physician approval for participation

Exclusion criteria

• Knee extension or ankle dorsiflexion contractures greater than 15 degrees
• Immunodeficiency or hematologic condition
• Allergy to AZA or mannitol
• Plans to receive a vaccine within 30 days of the planned AZA or placebo injection to take place at week 5
• Pregnancy
• Orthopedic surgery on the lower limbs completed in the prior 12 months
• New implanted device (e.g., baclofen pump) and/or active intrathecal medication titration that may affect muscle spasticity
• Botulinum toxin treatment within 3 months preceding enrollment unless given approval by the study physician
• Severe osteoporosis unless given approval by the study physician
• Current enrollment in a conflicting research study
• Any other health condition or diagnosis not listed above that may put the participant at risk as determined by the PI or study physician