Clinical trial NCT04664790: Hyperbaric Oxygen Therapy Compared to Cognitive Training in FASD
Official title: Hyperbaric Oxygen Therapy vs. Cognitive Training for Fetal Alcohol Spectrum Disorder; A Prospective, Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: FASD
Lead sponsor: Assaf-Harofeh Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-12-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive health assessment (NeuroTrax)
timeFrame: baseline, 3 months
measure: Executive functions and self-regulation in everyday environment
timeFrame: baseline, 3 months
Secondary outcomes:
measure: Brain perfusion
timeFrame: baseline, 3 months
measure: Brain microstructure - (MD)
timeFrame: baseline, 3 months
measure: Brain microstructure - (FA)
timeFrame: baseline, 3 months
measure: Brain function imaging
timeFrame: baseline, 3 months
measure: Metabolic Brain function imaging
timeFrame: baseline, 3 months
measure: Depression anxiety and stress
timeFrame: baseline, 3 months, 6 months
measure: Interpersonal Reactive Index (IRI)
timeFrame: baseline, 3 months, 6 months
measure: Difficulties in Emotion Regulation Scale (DERS)
timeFrame: baseline, 3 months, 6 months
measure: Mental Health Continuum (MHC-SF)
timeFrame: baseline, 3 months, 6 months
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:
citation: Goodlett CR, Horn KH. Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Res Health. 2001;25(3):175-84.
citation: Efrati S, Ben-Jacob E. Reflections on the neurotherapeutic effects of hyperbaric oxygen. Expert Rev Neurother. 2014 Mar;14(3):233-6. doi: 10.1586/14737175.2014.884928. Epub 2014 Jan 29.
citation: Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, Kliakhandler K, Kamiager I, Gal N, Friedman M, Ben-Jacob E, Golan H. Hyperbaric oxygen induces late neuroplasticity in post stroke patients--randomized, prospective trial. PLoS One. 2013;8(1):e53716. doi: 10.1371/journal.pone.0053716. Epub 2013 Jan 15.
citation: Hadanny A, Bechor Y, Catalogna M, Daphna-Tekoah S, Sigal T, Cohenpour M, Lev-Wiesel R, Efrati S. Hyperbaric Oxygen Therapy Can Induce Neuroplasticity and Significant Clinical Improvement in Patients Suffering From Fibromyalgia With a History of Childhood Sexual Abuse-Randomized Controlled Trial. Front Psychol. 2018 Dec 17;9:2495. doi: 10.3389/fpsyg.2018.02495. eCollection 2018.
citation: Hadanny A, Rittblat M, Bitterman M, May-Raz I, Suzin G, Boussi-Gross R, Zemel Y, Bechor Y, Catalogna M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions of post-stroke patients - a retrospective analysis. Restor Neurol Neurosci. 2020;38(1):93-107. doi: 10.3233/RNN-190959.
citation: Stoller KP. Quantification of neurocognitive changes before, during, and after hyperbaric oxygen therapy in a case of fetal alcohol syndrome. Pediatrics. 2005 Oct;116(4):e586-91. doi: 10.1542/peds.2004-2851. Epub 2005 Sep 15.
citation: Koren G, Golan C, Suzin G, Berkovich M, Efrati S. Effects of Hyperbaric Oxygen Therapy on Brain Perfusion, Cognition and Behavior in Fetal Alcohol Spectrum Disorder-A Case Study. Alcohol Alcohol. 2019 Mar 1;54(2):177-179. doi: 10.1093/alcalc/agz009.