Hyperbaric Oxygen Therapy Compared to Cognitive Training in FASD

FASD Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04664790
• Other study ID #: 275-20-ASF
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 1, 2024
• Est. completion date: January 1, 2025

Study information

• Verified date: November 2022
• Source: Assaf-Harofeh Medical Center
• Contact: Shai Efrati, Prof
• Phone: 97289779393
• Email: efratishai[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• FASD

Intervention

Device:
• Hyperbaric Oxygen
Each session will include exposure of 90 minutes to 100% at 2 ATA, with 5 minutes air breaks every 20 minutes

Behavioral:
• Cognitive training
Neuropsychologist guided BrainHQ training

Locations

Country	Name	City	State
Israel	Assaf-Harofeh Medical Center	Zerifin

Sponsors (1)

Lead Sponsor	Collaborator
Assaf-Harofeh Medical Center

Country where clinical trial is conducted

Israel, 

References & Publications (7)

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. — View 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. — View Citation

Goodlett CR, Horn KH. Mechanisms of alcohol-induced damage to the developing nervous system. Alcohol Res Health. 2001;25(3):175-84. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive health assessment (NeuroTrax)	Memory, attention and information process will be evaluated using the NeuroTrax computerized cognitive evaluation battery.	baseline, 3 months
Primary	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	Brain perfusion	Cerebral blood volume and flow will be measured using perfusion MRI protocol Dynamic susceptibility contrast (DSC).	baseline, 3 months
Secondary	Brain microstructure	Mean diffusivity (MD) will be evaluated using diffusion tensor imaging (DTI) MRI protocol.	baseline, 3 months
Secondary	Brain microstructure	Fractional anisotropy (FA) will be evaluated using diffusion tensor imaging (DTI) MRI protocol.	baseline, 3 months
Secondary	Brain function imaging	Resting state fMRI (rsfMRI), and task based fmri will evaluate brain function during a working memory task.	baseline, 3 months
Secondary	Metabolic Brain function imaging	Brain Single photon emission computed tomography (SPECT) will be conducted using Tc-99m-ECD.	baseline, 3 months
Secondary	Depression anxiety and stress	Evaluated using the Depression Anxiety Stress Scale Test (DASS 21) self-report instrument.	baseline, 3 months, 6 months
Secondary	Interpersonal Reactive Index (IRI)	The IRI questionnaire will be used to evaluate cognitive and affective aspects of empathic abilities.	baseline, 3 months, 6 months
Secondary	Difficulties in Emotion Regulation Scale (DERS)	The DERS questionnaire is a multidimensional self-report measure of emotion regulation	baseline, 3 months, 6 months
Secondary	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