An Evaluation of Hyperbaric Treatments for Children With Cerebral Palsy

Study Overview
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Brief Summary
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The study is to evaluate the effectiveness of hyperbaric treatments and the potential longer-term effects in children between the ages of 3 and 8 years with spastic cerebral palsy (CP). One group will receive 100% oxygen and the other group will receive the equivalent of 21% oxygen (room air). The children will receive pre-treatment testing (baseline). After 40 experimental treatments are completed, the children will be retested at 0, 3, and 6 months to evaluate any changes.

Detailed Description
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The study proposed herein is a randomized, double blind study to evaluate the therapeutic effectiveness of HBO in children (ages 3-8 years) with a diagnosis of spastic CP. Ninety-four children will be randomly assigned to either a hyperbaric oxygen treatment group or hyperbaric air treatment (HBA) group. Each group will receive 40 dives of 60 minutes duration each at 1.5 atmospheres of pressure (ATA) (the HBO group receiving 100% oxygen, and the HBA group receiving an air mixture containing 14% oxygen, which simulates 21% oxygen at 1.5 ATA). Neurological testing (Gross Motor Function Measure, Pediatric Evaluation of Disability Inventory, and the Test of Variables of Attention) will be performed at baseline, immediately after experimental treatment #40, and at 3 and 6 months after experimental treatment #40. Statistical analysis will be performed on these test data to determine any changes from baseline, or between group differences, in the functional capabilities of the study subjects.

Official Title
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An Evaluation of the Therapeutic Effectiveness of Hyperbaric Oxygen Treatments and Hyperbaric Air Treatments for Children With Cerebral Palsy

Conditions
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Cerebral Palsy, Cerebral Palsy, Spastic

Intervention / Treatment
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* Device: Hyperbaric Oxygen Treatment
* Device: Hyperbaric Air Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female children, ages 3 to 8 years with a diagnosis of spastic cerebral palsy. No documented evidence of hypoxic-ischemic encephalopathy (HIE). Hypoxic-ischemic encephalopathy (HIE) is not one of the major causes of CP. Medically cleared to participate. Your child's primary care physician will be asked to medically clear your child before entering the study. Able to pass pretest screening exercise. Each child will undergo the following screening exercise to determine the likelihood of being able to participate in the study: In order to assess ability to tolerate the placement of the oxygen hood in the hyperbaric setting, a hyperbaric oxygen hood will be placed upon the shoulders, or body of your child (depending upon size of your child) and with encouragement and comforting by you and study nurse, the child will be asked to maintain the placement of the hood for 15 minutes. Each child will be asked to blow through a straw, blow the nose, drink through a straw, or to swallow on command. Exclusion Criteria: Any previous HBO treatments. Thoracic surgery within 6 months of beginning the study. Unstable epilepsy as determined by a history of having had more than one major motor (generalized or partial tonic/clonic) seizure within the past six months. Having multiple motor seizures, requiring more than three anticonvulsant drugs for seizure control; or requiring changes in seizure medications more than once per month. Significant pulmonary dysfunction as determined by a history of chronic pulmonary disease, cystic fibrosis, interstitial lung disease, or chronic shortness of breath or cough. Uncontrolled asthma/reactive airway disease. Significant behavioral problems requiring medication. Any major congenital deformities of the brain or spinal cord. Active pneumothorax (collapsed lung). Recent cancer treatment with cisplatinum, bleomycin, or doxorubicin. Certain heart problems that cause the heart to pump poorly as determined by a history of congenital heart disease, cardiomyopathy, or symptoms of chest pain, dizziness, and shortness of breath. Optic neuritis. Diabetics requiring insulin therapy. Spherocytosis. Major GI reflux with frequent emesis. Botulinum toxin A (Botox) treatments within 6 months of entering study. Before entering the study, we will require that chronic medications be unchanged for the prior three months except for minor dosage adjustments.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric Oxygen Treatment (HBO)<br>100% oxygen at 1.5 ATA for 60 mins, Mon-Fri, 40 treatments total | Device: Hyperbaric Oxygen Treatment<br>* 100% oxygen at 1.5 ATA for 60 mins, Mon-Fri, 40 treatments total<br>* Other names: HBO;|
| Active Comparator: Hyperbaric Air Treatment (HBA)<br>14% oxygen at 1.5 ATA for 60 mins, Mon-Fri, 40 treatments total | Device: Hyperbaric Air Treatment<br>* 14% oxygen at 1.5 ATA for 60 mins, Mon-Fri, 40 treatments total<br>* Other names: HBA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Total Score (GMFM-88). | GMFM-88: total percent score on 88 items (I) of motor function grouped into 5 dimensions: A) lying and rolling (17 I), B) sitting (20 I), C) crawling and kneeling (14 I), D) standing (13 I), E) walking, running, jumping (24 I). Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Scores in each dimension determined by dividing score obtained by maximum possible score for that dimension, and multiplying by 100. Range is 0-100% for each: the higher the percent score, the greater the functional ability. Dimension scores and total GMFM-88 score calculated as: A) lying and rolling: (score achieved/51)x100 B) sitting: (score achieved/60)x100 C) crawling and kneeling: (score achieved/42)x100 D) standing: (score achieved/39)x100 E) walking, running, and jumping: (score achieved/72)x 100 GMFM-88 = (%A+%B+%C+%D+%E)/number of dimensions GMFM-66: [(total score on subset of 66 items/198)x100] | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure 66-Item Subscale Score (GMFM-66). | GMFM-66: total percent score on 66-item subscale of GMFM-88: Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score determined by dividing score obtained by maximum possible score for the 66 items, and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. GMFM-66: [(total score on subset of 66 items/198)x100]. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Dimension A | Total percent score on 17 items of GMFM grouped into Dimension A) lying and rolling. Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score in Dimension A determined by dividing score obtained by maximum possible score for that dimension (51), and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. A) lying and rolling: (score achieved/51)x100. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Dimension B | Total percent score on 20 items of GMFM grouped into Dimension B) sitting. Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score in Dimension B determined by dividing score obtained by maximum possible score for that dimension (60), and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. B) sitting: (score achieved/60)x100. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Dimension C | Total percent score on 14 items of GMFM grouped into Dimension C) crawling and kneeling. Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score in Dimension C determined by dividing score obtained by maximum possible score for that dimension (42), and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. C) crawling and kneeling: (score achieved/42)x100. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Dimension D | Total percent score on 13 items of GMFM grouped into Dimension D) standing. Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score in Dimension D determined by dividing score obtained by maximum possible score for that dimension (39), and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. D) standing: (score achieved/51)x100. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Score (Post-treatment Minus Pre-treatment) on Gross Motor Function Measure Dimension E | Total percent score on 24 items of GMFM grouped into Dimension E) walking, running, and jumping. Each item scored on 0-3 scale: 0 = does not initiate, 1 = initiates, 2 = partially completes, 3 = completes. Score in Dimension E determined by dividing score obtained by maximum possible score for that dimension (72), and multiplying by 100. Range is 0-100%: the higher the percent score, the greater the functional ability. E) walking, running, and jumping: (score achieved/72)x 100. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills: Self-care | Primary caregiver-reported (through structured interview) child capabilities for 73 items of functional skills grouped under self-care. Scores are 0 = unable to perform; 1 = capable of performing. Scores range from 0-73 and are rescaled to a 0-100% scale. Higher scores indicate greater abilities. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills: Mobility | Primary caregiver-reported (through structured interview) child capabilities for 59 items of functional skills grouped under mobility. Scores are 0 = unable to perform; 1 = capable of performing. Scores range from 0-59 and are rescaled to a 0-100% scale. Higher scores indicate greater abilities. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Functional Skills: Social Function | Primary caregiver-reported (through structured interview) child capabilities for 65 items of functional skills grouped under social function. Scores are 0 = unable to perform; 1 = capable of performing. Scores range from 0-65 and are rescaled to a 0-100% scale. Higher scores indicate greater abilities. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Caregiver Assistance: Self-care | Primary caregiver-reported (through structured interview) amount of caregiver assistance required by child to complete 8 items of daily activity grouped under self-care. Scores are 0 = total assistance, 1 = maximal assistance, 3 = minimal assistance, 4 = supervise/prompt/monitor, 5 = independent. Total scores range from 0-40 and are rescaled to 0-100%. Higher scores indicate greater ability to perform independently. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Caregiver Assistance: Mobility | Primary caregiver-reported (through structured interview) amount of caregiver assistance required by child to complete 7 items of daily activity grouped under mobilityare. Scores are 0 = total assistance, 1 = maximal assistance, 3 = minimal assistance, 4 = supervise/prompt/monitor, 5 = independent. Total scores range from 0-35 and are rescaled to 0-100%. Higher scores indicate greater ability to perform independently. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups (HBO Minus HBA) in Change in Scores (Post-treatment Minus Pre-treatment) on Pediatric Evaluation of Disability Inventory (PEDI) Caregiver Assistance: Social Function | Primary caregiver-reported (through structured interview) amount of caregiver assistance required by child to complete 5 items of daily activity grouped under social function. Scores are 0 = total assistance, 1 = maximal assistance, 3 = minimal assistance, 4 = supervise/prompt/monitor, 5 = independent. Total scores range from 0-25 and are rescaled to 0-100%. Higher scores indicate greater ability to perform independently. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups in Change in Scores (Post-treatment Minus Pre-treatment) on the Test of Variables of Attention (TOVA): Number of Correct Responses. | One of 4 parts of the TOVA, a computerized continuous performance test that measures attention and impulsivity in visual mode. Measures the number of times a target is correctly selected when it appears on a screen. Score ranges from 0-160; higher scores represent greater number of correct responses. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups in Change in Scores (Post-treatment Minus Pre-treatment) on the Test of Variables of Attention (TOVA): Number of Correct Nonresponses. | One of 4 parts of the TOVA, a computerized continuous performance test that measures attention and impulsivity in visual mode. Measures the number of times a target is correctly not selected (number of times a child correctly refrains from hitting a buzzer) when it appears on a screen. Score ranges from 0-160; higher scores represent greater number of correct nonresponses. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups in Change in Scores (Post-treatment Minus Pre-treatment) on the Test of Variables of Attention (TOVA): Response Time in Milliseconds | One of 4 parts of the TOVA, a computerized continuous performance test that measures attention and impulsivity in visual mode. Measures the processing time in milliseconds that it takes to correctly respond to a target. Lower times represent better response times. Range = 0 - 2000 milliseconds | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 
| The Difference Between Groups in Change in Scores (Post-treatment Minus Pre-treatment) on the Test of Variables of Attention (TOVA): Response Time Variability in Milliseconds | One of 4 parts of the TOVA, a computerized continuous performance test that measures attention and impulsivity in visual mode. Measures the variability in processing time in milliseconds that it takes to correctly respond to a target. Response time variability = the standard deviation of response times for correct responses. Lower values represent less variability and better responses. Range of response times = 0-2000 milliseconds. | Baseline (within 1 week of starting 8-week treatment period) and post-treatment (within 1 week of ending 8-week treatment period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Palsy, Spastic Cerebral Palsy, CP, Hyperbaric, HBOT