Clinical trial NCT02167022: Intense Physiotherapies to Improve Function in Young Children With Cerebral Palsy
Official title: Intense Physiotherapies to Improve Function in Young Children With Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cerebral Palsy
Keywords: intense therapy
brain plasticity
Perception-Action approach
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: Tucson Medical Center
name: Phoenix Children's Hospital
name: United Cerebral Palsy-Central Arizona
name: Nemours Children's Hospital
First posted: 2014-06-18
Enrollment: 90
Sex: ALL
Minimum age (years): 12
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cerebral palsy (CP) is a non-progressive disorder caused by an insult or injury to the brain when the brain is most rapidly developing and which results in some motor dysfunction. Causes for the injury to the brain are numerous and can occur prior to birth, during the birth process, or within the first few months following birth. The motor dysfunction can involve any or all four extremities but most often affects the legs, causing abnormal ambulation. The level of severity depends on the extent of the injury to the brain and can be mild to severe. In severe instances, the child is dependent on others for all his/her care.

There is no known cure for CP, but physical and occupational therapies are administered in an attempt to improve function. The frequency of these therapies varies from once a week (the standard of care in the Western Hemisphere) to five times a week (the standard of care in Asia and some Eastern European countries). The current understanding of brain plasticity offers a theoretical explanation to justify the more intense approach. Active repetitive motor skill-directed rehabilitation utilizes the plasticity of the brain and can restore some function. Intense active physiotherapy can stimulate non-injured but 'dormant' neurons and prevent their 'natural' degeneration in order for them to substitute for the function of injured neurons. It is the very young brain that is most likely to respond to this therapy.

The aim of this proposal is to evaluate the effect of administering both physical and occupational therapy five times each week for 12 weeks and compare it with the standard of care (SOC) approach of one time each week in children between the ages of 12 months and 36 months. This is the first randomized crossover trial to both enroll this young a population of children with cerebral palsy as well as to evaluate this approach from both the therapists and the parents perspectives. The number of children that this study will enroll is larger than in most CP studies. The children will be evaluated clinically with two validated instruments, one of which was designed specifically for children with CP and is administered and scored by certified therapists and the other which was designed for children with developmental disabilities and is scored by the child's care provider. A sub-set of children will have a special type of MRI to evaluate any changes in the neurological structure of the brain.

The Department of Pediatrics at the University of Arizona recently completed a collaborative study with the Neurologic Department at the Beijing Children's Hospital where the intense approach of five therapies per week is the SOC. The positive results prompted another investigation to determine if such an approach would be feasible in the United States. A compliance rate of 81% confirmed feasibility and the perception that parents who have a child diagnosed with CP will do whatever they can to improve their child's motor function.

Detailed description: Specific Aim #1: To compare the effectiveness of an intense physiotherapy program with the current standard of care in the management of children with spastic cerebral palsy.

Hypothesis #1: Children receiving a short cluster of intense therapies (5 times per week for 12 weeks) will show greater functional gains as determined by the Gross Motor Function Measure (GMFM-66) and the Pediatric Evaluation Disability Inventory (PEDI) than those receiving the same therapies once a week, the current standard of care.

Specific Aim #2: To determine if the functional gains by children with spastic cerebral palsy achieved with an intense physiotherapy program will continue to improve while receiving less intense standard weekly therapies for at least 36 weeks (9 months) following completion of the intense program.

Hypothesis #2: Motor skills gained after 12 weeks of intensely administered physiotherapies as determined by the GMFM and the PEDI will continue to improve at a rate greater than that seen in children receiving the same therapies once a week, the current standard of care.

Specific Aim #3: After receiving the same number of therapies at the end of the 48-week protocol, children receiving the intense series of therapies during the first 12-weeks will have made greater functional gains than those receiving them during the last 12-weeks.

Hypothesis #3: Children who receive intense physiotherapies at an earlier age make greater gains then those who receive the same therapies at a later age.

Specific Aim #4: To develop a clinical profile that will identify those children most likely to benefit from intensely administered physiotherapies.

Hypothesis #4: Clinical and radiologic characteristics play a major role in response to therapy.

Explorative Aim: To assess the correlation between clinical improvement from intense physiotherapies and anatomical changes using magnetic resonance imaging (MRI).

Hypothesis: The improvements from intense physiotherapies seen in the clinical assessments will be reflected by alterations of brain connectivity parameters available from neuroanatomical MRI and diffusion tensor imaging (DTI).

Eligibility criteria: Inclusion Criteria:

1. Age: 12 to 36 months of age (The diagnosis of CP is often uncertain under the age of 12 months. The cutoff at 36 months is to have a population of young children when the brain is most "plastic" and most susceptible to reorganization).
2. Diagnosis: Diagnosis of spastic CP confirmed by a pediatric neurologist or pediatric rehabilitation specialist.
3. Etiology: The insult to the central nervous system that caused the motor dysfunction must have occurred during gestation or within one year after birth independent of gestational age.
4. Disease severity level: Gross Motor Function Classification System (GMFCS) levels I, II and III.

Exclusion Criteria:

1. Diagnosis: Diagnosis of CP secondary to neuronal migration.
2. Co-morbidities: Medical conditions that may prevent the administration of rehabilitation therapies at the intensity required by the study, or that may compromise the study ability to maintain blindness, or that have a co-morbidity not typically associated with CP (i.e. cancer, cystic fibrosis).
3. Co-interventions: Anticipated pharmacological intervention or procedure or participation in other studies that may interfere with this study.

Primary outcomes:
measure: Change in Gross Motor Function Measure-66 (GMFM-66)
timeFrame: Change from Baseline at 12 weeks, 24 weeks, 36 weeks, and 48 weeks
Secondary outcomes:
measure: Change in Pediatric Evaluation of Disability Inventory-Functional Skills (PEDI-FS)
timeFrame: Change from Baseline at 12 weeks, 24 weeks, 36 weeks, and 48 weeks
Other outcomes:
measure: Change in Magnetic Resonance Imaging (MRI)/Diffusion Tensor MRI (DTI)
timeFrame: Change from Baseline at 36 weeks
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Phoenix
country: United States
facility: United Cerebral Palsy-Central Arizona
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
Study officials:
affiliation: University of Arizona
name: Burris R Duncan, MD
role: PRINCIPAL_INVESTIGATOR
References: