Clinical trial NCT03339037: Hyperbaric Oxygen Therapy Effect on Post Concussion Syndrome in Children
Official title: Application of Hyperbaric Oxygen Therapy for Children Suffering From Prolonged Post-Concussion Syndrome Due to Mild Traumatic Brain Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hyperbaric Oxygen Therapy
Traumatic Brain Injury
Post-Concussion Syndrome
Keywords: HBOT
TBI
pediatrics
PCS
PPCS
concussion
traumatic brain injury
hyperbaric oxygen
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2017-11-13
Enrollment: 52
Sex: ALL
Minimum age (years): 8
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: randomized controlled trial using a SHAM treatment compared to treatment
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cognitive function
timeFrame: at 3 months
measure: Cognitive function
timeFrame: at 6 months
Secondary outcomes:
measure: Post concussion syndrome symptoms
timeFrame: baseline, 3 months and 6 months from baseline
measure: Health Behaviour inventory
timeFrame: baseline, 3 months and 6 months from baseline
measure: Balance
timeFrame: baseline, 3 months and 6 months from baseline
measure: Brain functional imaging
timeFrame: baseline, 3 months
measure: Brain microstructural imaging
timeFrame: baseline, 3 months and 6 months from baseline
measure: Brain perfusion
timeFrame: baseline, 3 months and 6 months from baseline
measure: Short form health survey (PedsQL)
timeFrame: baseline, 3 months and 6 months from baseline
measure: Brain network analysis
timeFrame: baseline, 3 months and 6 months from baseline
measure: Behaviour
timeFrame: baseline, 3 months and 6 months from baseline
measure: Executive functions
timeFrame: baseline, 3 months and 6 months from baseline
Other outcomes:
Locations:
city: Zerifin
country: Israel
facility: Assaf-Harofeh Medical Center
Study officials:
affiliation: Asaf-Harofhe MC
name: Shai a Efrati, MD
role: PRINCIPAL_INVESTIGATOR
References: