Hyperbaric Oxygen Therapy Compared to Cognitive Training in FASD

Study Overview
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Brief Summary
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Fetal Alcohol Spectrum Disorder (FASD) describes a wide range of adverse physical, behavioral and cognitive effects resulting from prenatal alcohol exposure (PAE) during embryonic and fetal development. A number of clinical studies have presented evidence regarding the physiological effects of HBOT on metabolically dysfunctional brain regions that might be related to FASD. The aim of the study is to compare the effect of HBOT vs. neurocognitive training on neurobehavioral function in FASD.

Detailed Description
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Fetal Alcohol Spectrum Disorder (FASD) describes a wide range of adverse physical, behavioral and cognitive effects resulting from prenatal alcohol exposure (PAE) during embryonic and fetal development. Currently individuals afflicted by FASD are treated symptomatically for ADHD and different forms of disruptive behavior. However, these approaches have not succeeded in improving the long-term clinical outcome [1]. A number of clinical studies have presented evidence regarding the physiological effects of hyperbaric oxygen therapy (HBOT) on metabolically dysfunctional brain regions that might be related to FASD [2-5]. Case studies conducted using HBOT suggested a potential safe and efficient treatment for FESD [6-7]. The aim of the study is to compare the effect of HBOT vs. neurocognitive training on neurobehavioral function in FASD. The study is designed as a prospective randomized, two active arm trial. After enrolment, eligible participants will be randomized with equal probability into one of two arms: HBOT or cognitive training arm. The evaluation procedure will be performed twice, at baseline and 1-3 weeks after the last treatment session, and includes cognitive tests, FASD relegated questionnaires, and anatomical and functional brain imaging (MRI and SPECT). The study is designed as an intention to treat trial, and thus, patients will be included in the analysis if they completed at least one HBOT/cognitive training session, and attained post treatment study analysis. The HBOT protocol will be administrated in a multi-place chamber. The protocol comprised of 60 daily sessions, 5 sessions per week within a three month period. Each session includes breathing 100% oxygen by mask at 2ATA for 90 minutes with 5-minute air breaks every 20 minutes. The cognitive training protocol contains a neuropsychologist guided BrainHQ training program. This is a 3 months program that includes 30 minutes sessions at least 3 times per week.

Official Title
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Hyperbaric Oxygen Therapy vs. Cognitive Training for Fetal Alcohol Spectrum Disorder; A Prospective, Randomized Clinical Trial

Conditions
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FASD

Intervention / Treatment
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* Device: Hyperbaric Oxygen
* Behavioral: Cognitive training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject willing and able to sign an informed consent Age 18 years and older Diagnosed with FASD by an Israeli expert Failure to improve after at least one line of conventional therapy Stable psychological and pharmacological treatment for over three months prior to inclusion Exclusion Criteria: Inability to attend scheduled clinic visits and/or comply with the study protocol History of other brain pathologies Active malignancy Serious suicidal ideation Severe or unstable physical disorders at baseline History of HBOT for any reason prior to study enrollment Chest pathology incompatible with pressure changes (including active asthma) Inner ear disease Contraindications for MRI or inability to perform an awake brain MRI

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hyperbaric Oxygen<br>60 daily hyperbaric oxygen treatment sessions will be administrated 5 days per week. | Device: Hyperbaric Oxygen<br>* Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes<br>|
| Active Comparator: Cognitive training<br>Neuropsychologist guided cognitive training. | Behavioral: Cognitive training<br>* Neuropsychologist guided BrainHQ training<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive health assessment (NeuroTrax) | Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery. | baseline, 3 months | 
| Executive functions and self-regulation in everyday environment | Evaluated using the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A) self-reported questionnaire | baseline, 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain perfusion | Cerebral blood volume and flow will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC). | baseline, 3 months | 
| Brain microstructure | Mean diffusivity (MD) will be evaluated using diffusion tensor imaging (DTI) MRI protocol. | baseline, 3 months | 
| Brain microstructure | Fractional anisotropy (FA) will be evaluated using diffusion tensor imaging (DTI) MRI protocol. | baseline, 3 months | 
| Brain function imaging | Resting state fMRI (rsfMRI), and task based fmri will evaluate brain function during a working memory task. | baseline, 3 months | 
| Metabolic Brain function imaging | Brain Single photon emission computed tomography (SPECT) will be conducted using Tc-99m-ECD. | baseline, 3 months | 
| Depression anxiety and stress | Evaluated using the Depression Anxiety Stress Scale Test (DASS 21) self-report instrument. | baseline, 3 months, 6 months | 
| Interpersonal Reactive Index (IRI) | The IRI questionnaire will be used to evaluate cognitive and affective aspects of empathic abilities. | baseline, 3 months, 6 months | 
| Difficulties in Emotion Regulation Scale (DERS) | The DERS questionnaire is a multidimensional self-report measure of emotion regulation | baseline, 3 months, 6 months | 
| Mental Health Continuum (MHC-SF) | The MHC-SF questionnaire will be used to assess three components of well-being: emotional, social, and psychological and conduct categorical diagnosis of positive mental health. | baseline, 3 months, 6 months |