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Hyperbaric Oxygen Therapy Effect on Post Concussion Syndrome in Children (TBIPED)

Primary Purpose

Hyperbaric Oxygen Therapy, Traumatic Brain Injury, Post-Concussion Syndrome

Status
Terminated
Phase
Not Applicable
Locations
Israel
Study Type
Interventional
Intervention
Hyperbaric oxygen therapy
Normobaric air SHAM
Sponsored by
Assaf-Harofeh Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hyperbaric Oxygen Therapy focused on measuring HBOT, TBI, pediatrics, PCS, PPCS, concussion, traumatic brain injury, hyperbaric oxygen

Eligibility Criteria

8 Years - 16 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • - Ages 8-15
  • Mild TBI (defined as loss of consciousness with duration of 0-30 minutes, post-traumatic amnesia with duration of less than 24 hours, Glasgow Coma Scale grade of 13-15) within 6 months-3 years prior to the inclusion in the study.
  • Moderate TBI -Patients with a GCS of 9-12 a as well as additional criteria such as CT abnormalities and admission to hospital
  • Presence of at least two PCS as measured by the Post-Concussion Symptom Inventory )see attached) (there's a RCT now recruitingwith at least 1 and not 2) for at least 3 months.
  • No change in cognitive or behavioral functions during one month prior to the beginning of the study (according to parents/teachers report).

Screening protocol:

After signing the informed consent (signed by the parents), patients will undergo computerized cognitive tests using the computerized Neurotrax in patients over 10, and standard pen and paper cognitive tests in patients under 10. Patients who fulfill inclusion criteria will be included in the study.

Inclusion criteria:

- Objective cognitive impairment: a decrease of at least 1 standard deviation (SD) from same age mean score in one or more of the following indices : memory, attention, information processing speed, executive functions in both Neurotrax

Exclusion Criteria:

  • - Dynamic neurologic improvement or worsening during the past month (according to parents/teachers report);
  • Had been treated with HBOT for any other reason prior to their inclusion;
  • Chest pathology incompatible with pressure changes (including asthma)
  • Inner ear disease;
  • Claustrophobia;
  • Inability to perform awake brain MRI test
  • Previous neurologic conditions (eg. Epilepsy, neuromuscular diseases, metabolic diseases, etc.)
  • Brain tumors
  • Skull base fractures
  • Active malignancy
  • s/p neurosurgery that included: ventricular drainage, subdural hematomas drainage, epidural hematomas drainage, intracerebral hemorrhage evacuation. Depressed fracture surgery, won't be excluded.
  • Encephalomalacia per MRI imaging
  • No informed consent

Sites / Locations

  • Assaf-Harofeh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Hyperbaric oxygen therapy

Normobaric air SHAM

Arm Description

60 Hyperbaric oxygen sessions in a multiplace hyperbaric chamber (HAUX-Life-Support GmbH). each session 1.5 ATA of 100% oxygen for 1 hour. 1 meter per minute compression and decompression.

60 sessions in a multiplace hyperbaric chamber (HAUX-Life-Support GmbH). Each session at 1 ATA of 21% oxygen (air) for 1 hour. 1 meter per minute compression and decompression. after 3 months, patients will be crossed over and treated with 60 sessions of treatment

Outcomes

Primary Outcome Measures

Cognitive function
General,Attention, Memory, Executive functions, Visual spatial and Verbal memory indices Index (scale 0-100) will be measured using the computerized standardized Neurotrax battery test. Each of above cognitive indices is computed as a normalized combined score of 2-3 cognitive tests. (At baseline, this battery will be conducted as part of the screening in patients over 10).
Cognitive function
General,Attention, Memory, Executive functions, Visual spatial and Verbal memory indices Index (scale 0-100) will be measured using the computerized standardized Neurotrax battery test. Each of above cognitive indices is computed as a normalized combined score of 2-3 cognitive tests. (At baseline, this battery will be conducted as part of the screening in patients over 10).

Secondary Outcome Measures

Post concussion syndrome symptoms
Patients and their parents will fill questionaries' Postconcussion Symptom Inventory (PCSI) (scale 0-21) at baseline and at their second and/or third evaluations
Health Behaviour inventory
Patients and their parents will fill questionaries' Health Behaviour inventory (scale 50-200) at baseline and at their second and/or third evaluations
Balance
Patients will undergo balance tests (BERG Balance Scale) (scale 0-56) at each of the evaluations
Brain functional imaging
Patients will undergo photon emission tomography (PET-CT) using FDG at each of the three evaluations
Brain microstructural imaging
Imaging will be conducted in using a 3 Tesla system (Siemens, Germany). The MRI protocol includes the following sequences: Axial T1, T2, FLAIR, Axial Diffusion weighted, Axial T1-PostGadollinium , dynamic contrast enhancement (DSC), diffusion tensor imaging (DTI)
Brain perfusion
Imaging will be conducted in using a 3 Tesla system (Siemens, Germany). The MRI protocol includes the following sequences: Axial T1, T2, FLAIR, Axial Diffusion weighted, Axial T1-PostGadollinium , dynamic contrast enhancement (DSC), diffusion tensor imaging (DTI)
Quality of life
Patients and their parents will complete questionnaires Pediatric Quality of Life inventory (PedsQL) - multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning.
Brain network analysis
Patients will undergo resting state EEG as well as EEG during performing cognitive tasks ,using a 64 electrodes cap.
Behaviour
The parents and their teachers will complete the following questionnaire at baseline and at their second and/or third evaluations. The rating scales are available for parent (Conners 3-P), teacher (Conners 3-T) and self-report (Conners 3-SR).Subscales include inattention, hyperactivity/impulsivity, learning, executive functioning, aggression and peer relations, as well as subscales mapping onto DSM-IV criteria for ADHD (inattentive), ADHD (hyperactive-impulsive), ADHD combined, Conduct Disorder, and Oppositional-Defiant Disorder. Means and standard deviations for the global index vary dependent on age (for 6 year-olds the mean is 5.15 with a standard deviation of 3.97; means for 17 to 18 year-olds are 3.90 with a standard deviation of 4.00). Raw scores are usually converted to T-scores or percentile scores relative to normative data. T-scores above 60 (percentiles above 84) are considered clinically significant.
Executive functions
The parents and their teachers will complete the Behavior Rating Inventory of Executive Function(BRIEF) questionnaire at baseline and at their second and/or third evaluations. he Global Executive Composite (GEC) is an overarching summary score that incorporates all of the BRIEF clinical scales. The possible range of scores for teachers is 0 to 24.

Full Information

First Posted
October 22, 2017
Last Updated
May 31, 2022
Sponsor
Assaf-Harofeh Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT03339037
Brief Title
Hyperbaric Oxygen Therapy Effect on Post Concussion Syndrome in Children
Acronym
TBIPED
Official Title
Application of Hyperbaric Oxygen Therapy for Children Suffering From Prolonged Post-Concussion Syndrome Due to Mild Traumatic Brain Injury
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Terminated
Why Stopped
Recruitment difficulties - patients refusal to sham controlled
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
November 1, 2021 (Actual)
Study Completion Date
May 20, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assaf-Harofeh Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Due its high incidence, mTBI and its consequences of PPCS are a major public health issue. There is no consensus regarding the treatment of PPCS in pediatrics. Relying on its results in adults, HBOT offers a promising new direction of treatment, which targets the basic pathological processes responsible for post-concussion symptoms. The effect of hyperbaric oxygen therapy in pediatric TBI has never been evaluated. The aim of the current study is to evaluate in a prospective cross-over, randomized study, the effect of HBOT on children with PPCS due to mild TBI.
Detailed Description
The study is designed as a prospective, randomized, controlled, cross-over two groups trial. The study will be conducted in the -Sagol center for hyperbaric medicine and research and the children neurological unit of Assaf Harofeh Medical Center, Israel. Brain MRIs evaluation will be done the radiology department of Assaf-Harofeh Medical Center, Israel. Study will include 70 patients After signing the informed consent (signed by the parents), patients will undergo computerized cognitive tests using the computerized Neurotrax and Moxo cognitive batteries. Patients who fulfill inclusion criteria will be included in the study. After signing informed consent (by parents, at the prescreening phase), patients who fill inclusion criteria, will be randomized in 1:1 manner into the treated or the control-cross group. Randomization will be performed using a computer software according to patient id. After the randomization, patients will be invited for baseline evaluation that will include full review of their medical status and complete physical examination. All patients will go through evaluation of their neurocognitive function using further neurocognitive testing battery, questionnaires and brain imaging (perfusion MRI+DTI, SPECT). In cases of brain tumors, skull base tumors, encephalomalacia findings in MRI, patients will be excluded. The patients in the treated group will be evaluated three time - at baseline, after 3 months of HBOT treatment and after another consequent 3 months period from treatment (6 months from baseline). The patients of the cross group will be evaluated three times as well- at baseline, after 3 month control period without hyperbaric treatment and after a consequent 3 month period of HBOT treatment. The following HBOT treatment protocol will be practiced: The patients will go through 60 HBOT treatments (each treatment session will be given on a separate day), distributed over three months (five days a week). Each session will be for 60 minutes in 100% oxygen atmosphere and at pressure of 1.5 ATA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperbaric Oxygen Therapy, Traumatic Brain Injury, Post-Concussion Syndrome
Keywords
HBOT, TBI, pediatrics, PCS, PPCS, concussion, traumatic brain injury, hyperbaric oxygen

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
randomized controlled trial using a SHAM treatment compared to treatment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
randomization by computer, sham/ treatment will be known to chamber technicians and nurses but not to investigators
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hyperbaric oxygen therapy
Arm Type
Active Comparator
Arm Description
60 Hyperbaric oxygen sessions in a multiplace hyperbaric chamber (HAUX-Life-Support GmbH). each session 1.5 ATA of 100% oxygen for 1 hour. 1 meter per minute compression and decompression.
Arm Title
Normobaric air SHAM
Arm Type
Sham Comparator
Arm Description
60 sessions in a multiplace hyperbaric chamber (HAUX-Life-Support GmbH). Each session at 1 ATA of 21% oxygen (air) for 1 hour. 1 meter per minute compression and decompression. after 3 months, patients will be crossed over and treated with 60 sessions of treatment
Intervention Type
Device
Intervention Name(s)
Hyperbaric oxygen therapy
Intervention Description
60 HBOT sessions at 2 ATA 100% oxygen
Intervention Type
Device
Intervention Name(s)
Normobaric air SHAM
Intervention Description
60 sessions at 1 ATA 21% oxygen (air)
Primary Outcome Measure Information:
Title
Cognitive function
Description
General,Attention, Memory, Executive functions, Visual spatial and Verbal memory indices Index (scale 0-100) will be measured using the computerized standardized Neurotrax battery test. Each of above cognitive indices is computed as a normalized combined score of 2-3 cognitive tests. (At baseline, this battery will be conducted as part of the screening in patients over 10).
Time Frame
at 3 months
Title
Cognitive function
Description
General,Attention, Memory, Executive functions, Visual spatial and Verbal memory indices Index (scale 0-100) will be measured using the computerized standardized Neurotrax battery test. Each of above cognitive indices is computed as a normalized combined score of 2-3 cognitive tests. (At baseline, this battery will be conducted as part of the screening in patients over 10).
Time Frame
at 6 months
Secondary Outcome Measure Information:
Title
Post concussion syndrome symptoms
Description
Patients and their parents will fill questionaries' Postconcussion Symptom Inventory (PCSI) (scale 0-21) at baseline and at their second and/or third evaluations
Time Frame
baseline, 3 months and 6 months from baseline
Title
Health Behaviour inventory
Description
Patients and their parents will fill questionaries' Health Behaviour inventory (scale 50-200) at baseline and at their second and/or third evaluations
Time Frame
baseline, 3 months and 6 months from baseline
Title
Balance
Description
Patients will undergo balance tests (BERG Balance Scale) (scale 0-56) at each of the evaluations
Time Frame
baseline, 3 months and 6 months from baseline
Title
Brain functional imaging
Description
Patients will undergo photon emission tomography (PET-CT) using FDG at each of the three evaluations
Time Frame
baseline, 3 months
Title
Brain microstructural imaging
Description
Imaging will be conducted in using a 3 Tesla system (Siemens, Germany). The MRI protocol includes the following sequences: Axial T1, T2, FLAIR, Axial Diffusion weighted, Axial T1-PostGadollinium , dynamic contrast enhancement (DSC), diffusion tensor imaging (DTI)
Time Frame
baseline, 3 months and 6 months from baseline
Title
Brain perfusion
Description
Imaging will be conducted in using a 3 Tesla system (Siemens, Germany). The MRI protocol includes the following sequences: Axial T1, T2, FLAIR, Axial Diffusion weighted, Axial T1-PostGadollinium , dynamic contrast enhancement (DSC), diffusion tensor imaging (DTI)
Time Frame
baseline, 3 months and 6 months from baseline
Title
Quality of life
Description
Patients and their parents will complete questionnaires Pediatric Quality of Life inventory (PedsQL) - multi-dimensional concept that includes domains related to physical, mental, emotional, and social functioning.
Time Frame
baseline, 3 months and 6 months from baseline
Title
Brain network analysis
Description
Patients will undergo resting state EEG as well as EEG during performing cognitive tasks ,using a 64 electrodes cap.
Time Frame
baseline, 3 months and 6 months from baseline
Title
Behaviour
Description
The parents and their teachers will complete the following questionnaire at baseline and at their second and/or third evaluations. The rating scales are available for parent (Conners 3-P), teacher (Conners 3-T) and self-report (Conners 3-SR).Subscales include inattention, hyperactivity/impulsivity, learning, executive functioning, aggression and peer relations, as well as subscales mapping onto DSM-IV criteria for ADHD (inattentive), ADHD (hyperactive-impulsive), ADHD combined, Conduct Disorder, and Oppositional-Defiant Disorder. Means and standard deviations for the global index vary dependent on age (for 6 year-olds the mean is 5.15 with a standard deviation of 3.97; means for 17 to 18 year-olds are 3.90 with a standard deviation of 4.00). Raw scores are usually converted to T-scores or percentile scores relative to normative data. T-scores above 60 (percentiles above 84) are considered clinically significant.
Time Frame
baseline, 3 months and 6 months from baseline
Title
Executive functions
Description
The parents and their teachers will complete the Behavior Rating Inventory of Executive Function(BRIEF) questionnaire at baseline and at their second and/or third evaluations. he Global Executive Composite (GEC) is an overarching summary score that incorporates all of the BRIEF clinical scales. The possible range of scores for teachers is 0 to 24.
Time Frame
baseline, 3 months and 6 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: - Ages 8-15 Mild TBI (defined as loss of consciousness with duration of 0-30 minutes, post-traumatic amnesia with duration of less than 24 hours, Glasgow Coma Scale grade of 13-15) within 6 months-3 years prior to the inclusion in the study. Moderate TBI -Patients with a GCS of 9-12 a as well as additional criteria such as CT abnormalities and admission to hospital Presence of at least two PCS as measured by the Post-Concussion Symptom Inventory )see attached) (there's a RCT now recruitingwith at least 1 and not 2) for at least 3 months. No change in cognitive or behavioral functions during one month prior to the beginning of the study (according to parents/teachers report). Screening protocol: After signing the informed consent (signed by the parents), patients will undergo computerized cognitive tests using the computerized Neurotrax in patients over 10, and standard pen and paper cognitive tests in patients under 10. Patients who fulfill inclusion criteria will be included in the study. Inclusion criteria: - Objective cognitive impairment: a decrease of at least 1 standard deviation (SD) from same age mean score in one or more of the following indices : memory, attention, information processing speed, executive functions in both Neurotrax Exclusion Criteria: - Dynamic neurologic improvement or worsening during the past month (according to parents/teachers report); Had been treated with HBOT for any other reason prior to their inclusion; Chest pathology incompatible with pressure changes (including asthma) Inner ear disease; Claustrophobia; Inability to perform awake brain MRI test Previous neurologic conditions (eg. Epilepsy, neuromuscular diseases, metabolic diseases, etc.) Brain tumors Skull base fractures Active malignancy s/p neurosurgery that included: ventricular drainage, subdural hematomas drainage, epidural hematomas drainage, intracerebral hemorrhage evacuation. Depressed fracture surgery, won't be excluded. Encephalomalacia per MRI imaging No informed consent
Facility Information:
Facility Name
Assaf-Harofeh Medical Center
City
Zerifin
ZIP/Postal Code
70300
Country
Israel

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Hyperbaric Oxygen Therapy Effect on Post Concussion Syndrome in Children

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