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

Official title

Smart Ankle-Foot Orthosis and 5-Azacitidine to Enhance Gait and Community Mobility for Children With Cerebral Palsy

Overview

This is an intervention study to investigate the impact of a smart ankle-foot orthosis (AFO) on mobility outcomes in children with Cerebral Palsy. Participants will complete a three phase protocol including 6-weeks of at home training with the smart AFO. Participants will also have the option to participate in a randomized control trial to investigate the impact of 5-Azacitidine combined with the smart AFO to further effect mobility outcomes.

Detailed description

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.

Interventions

• Device Smart Ankle-Foot Orthosis
  The Biomotum Ambulo is an adjustable smart AFO device featuring two adjustable spring settings and provides real-time biofeedback using footplate sensors and progressive goal parameters based on individual gait.
• Drug 5-Azacitidine
  A subset of opt-in participants will receive a single dose (75mg/m²) of 5-Azacitidine (AZA), an FDA-approved drug for pediatric oncology. A registered nurse will deliver a single subcutaneous injection at midpoint.
• Drug Placebo
  A subset of opt in participants will receive a single dose (75mg/m²) of Mannitol (placebo). A registered nurse will deliver a single subcutaneous injection at midpoint.

Primary outcome measures

• 6 Minute Walking Test [Time frame: Baseline to Follow-Up, approximately 13 weeks]

Secondary outcome measures (8)

• 10 Meter Walking Test [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Gross Motor Function Measure 88 (GMFM-88) [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Selective Control Assessment of the Lower Extremity (SCALE) [Time frame: Baseline to Post-Intervention, approximately 7 weeks]
• Pediatric Berg Balance Scale (BBS) [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Modified Tardieu Scale (MTS) [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Wong-Baker FACES Pain Rating Scale [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Pictorial Children's Effort Rating Table (PCERT) [Time frame: Baseline to Follow-Up, approximately 13 weeks]
• Cerebral Palsy Quality of Life Questionnaire (CP-QOL) [Time frame: Baseline to Follow-Up, approximately 13 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Other

Study locations

United States · 1 center

• Shirley Ryan AbilityLab — Chicago

Identifiers

NCT: NCT07434492 · STU00225131

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗