Hyperbaric Oxygen Therapy for Persistent Post Stroke Depression

Assaf-Harofeh Medical Center142 enrolled

Overview

The study evaluates the effect of HBOT on depression in patients suffering from persistent symptoms of post stroke depression (PSD) in an double blind sham control study.

Post-stroke depression (PSD) is a prevalent mental health complication, affecting approximately 33% of stroke survivors. Its occurrence not only hinders rehabilitation and recovery from motor and cognitive deficits post-stroke but also escalates the risk of subsequent neurovascular events. Both biological and psychological factors are instrumental in the onset of PSD. Ischemia plays a pivotal role in the development of long-term PSD due to its impact on specific brain regions, neurotransmitter systems, neural connectivity, inflammatory responses, and mitochondrial dysfunction. brain ischemia can instigate a protracted cycle of inflammation, levels and functions of neurotransmitters, impaired mitochondrial function, that directly impinges on the brain's ability to undergo neuroplastic changes. This relationship underscores the importance of targeting the cure of brain ischemia in therapeutic strategies for PSD. Managing the brain ischemia could potentially salvage neuroplasticity and mitigate the mental and cognitive decline associated with PSD. The new protocols of hyperbaric oxygen therapy (HBOT), using the hyperoxic-hypoxic paradox (HHP), is one of the first therapeutic intervention already in clinical use today for the specific goal of inducing regeneration of damaged brain tissue. Cumulative data from recent years provide convincing evidence that HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in post-stroke patients. Both neurological and cognitive functions were improved even years after the stroke. The observed restoration of neuronal activity in the metabolically dysfunctional stunned areas indicates that HBOT is a potent means of delivering sufficient oxygen needed for activation of neuroplasticty and restoration of impaired functions. HBOT was found to be effective in small clinical trials for patients suffering from post-stroke depression. In a meta-analysis done by Liang et al. the efficacy and safety of HBOT for PSD was evaluated. A total of 27 RCTs involving 2250 participants were identified. Patients in HBOT group had a higher response rate than patients in control group (response rate: 69.4% vs 51.2%, odds ratio \[OR\] = 2.51, 95% confidence interval \[CI\] \[1.83-3.43\], P = 0.000). HBOT significantly reduced Hamilton Depression (HAMD). The aim of the current study is to evaluate the effect of HBOT on depression in patients suffering from persistent symptoms of post stroke depression (PSD) in an double blind sham control study.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

142

Conditions

Post Stroke Depression

Interventions

hyperbaric oxygen therapyDEVICE

The HBOT protocol consists of 60 daily sessions, five times per week, each session lasting 90 minutes. Investigational product: Multiplace hyperbaric oxygen chamber (Haux, Germany) located at the Sagol Center for Hyperbaric Medicine and Research, Shamir (Assaf-Harofeh) Medical Center, Israel.

Eligibility

Sex: ALLMin age: 50 YearsMax age: 85 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age between 50 -85 2. Suffered an ischemic stroke 6 months to 7 years prior to their inclusion 3. Treated or being treated by antidepressants for at least 3 months 4. Diagnosis of PSD based on HDRS-17 score of 17 and above. 5. Stable psychological and pharmacological treatment for more than three months prior to inclusion. 6. Subject willing and able to read, understand and sign an informed consent. Exclusion Criteria: 1. Inability to attend scheduled clinic visits and/or comply with the study protocol 2. Diagnosis of a psychiatric disorder prior to the recent stroke including: major depression, schizophrenia or bipolar disease. 3. Diagnosis of aphasia or major cognitive decline 4. History of Deep brain stimulation (DBS) 5. History of traumatic brain injury, brain tumors, brain surgery, chronic subdural haemorrhages, Epilepsy 6. Active malignancy 7. Substance use at baseline. 8. History of other neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), Frontotemporal dementia (FTD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), Creutzfeld Jacob disease (CJD), Multisystem atrophy (MSA), Pseudobulbar palsy (PSP), Corticobasal degeneration (CBD), Wernicke Korsakoff syndrome 9. Serious suicidal ideation 10. Renal or liver insufficiency, electrolyte imbalances 11. Chronic heart failure with ejection fraction of 30 or less 12. HBOT for any reason prior to study enrolment 13. Chest pathology incompatible with pressure changes (including active asthma or COPD) 14. Ear or Sinus pathology incompatible with pressure changes (above 3 otolaryngologist visits a year) 15. An inability to perform an awake brain MRI 16. No evidence of vascular related lesions in the brain MRI 17. Active smoking 18. Participation in another study

Locations (1)

The Sagol Center for Hyperbaric Medicine and Research Shamir Medical Center (Assaf Harofeh)

Zrifin, Israel

RECRUITING

Outcomes

Primary Outcomes

PSD symptoms

Depression severity will be evaluated by structured interview based on the HDRS-17 guided structural questioner (Hamilton Depression Rating Scale from 0-53 ,Levels of depression is categorized according to the following accepted criteria: * Not depressed: 0-7 * Mild (subthreshold): 8-13 * Moderate: 14-18 * Severe: 19-22 * Very severe: \>23)

Time frame: Change from Baseline immediately after the intervention

Secondary Outcomes

depression

Beck depression inventory II. Each answer is scored on a scale value of 0 to 3 . The score ranges between 0 and 63, with higher scores indicating more severe depression symptoms.

Time frame: Change from Baseline immediately after the intervention

Short form health survey (sf-36)

Quality of life questionnaire, scale of 0-100, higher score means better outcome

Time frame: at baseline, 3 months, 6 months

psychological distress

The Brief Symptom Inventory-18 (BSI-18). self-report questionnaire which generates a summary scale, the global stress index (GSI), and three subscales: depression, anxiety, and somatization. Each item is rated on a 5-point scale, with distress ratings ranging from 0 (not at all) to 4 (extremely) .

Time frame: Change from Baseline immediately after the intervention

health status

Changes will be measured by The Stroke Impact Scale (SIS). The SIS version 3.0 includes 59 items, An extra question on stroke recovery asks that the client rate on a scale from 0 - 100 how much the client feels that he/she has recovered from his/her stroke.

Time frame: Change from Baseline immediately after the intervention

independent living skills

Central Contacts

Shai a Efrati, MD

CONTACT

972549212866 efratishai@outlook.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Changes will be measured by Instrumental Activities of Daily Living (IADL) Scale. There are eight domains of function measured with the Lawton IADL scale. Clients are scored according to their highest level of functioning in that category. A summary score ranges from 0 (low function, dependent) to 8 (high function, independent) for women, and 0 through 5 for men.

Time frame: Change from Baseline immediately after the intervention

NeuroTrax

computerized cognitive evaluation battery. each outcome parameter will be normalized and fit to an IQ-like scale (mean=100, STD=15), according to the participants' age and education.

Time frame: at baseline, 3 months

MoCA

Montreal Cognitive Assessment (MoCA). The maximum MoCA score is 30 points, with a 1-point scoring correction for individuals with 12 years of education or less. A score of 26 or above is considered normal and a score lower than 26 has been considered to be the optimal cutoff point for diagnosis of cognitive impairment.

Time frame: Change from Baseline immediately after the intervention

CANTAB Cambridge Neuropsychological Test Automated Battery

computerized cognitive evaluation battery test, divided into 2 tasks: 1- Multitasking test (MTT)- attention, reaction time and executive functions, Multitasking test Incongruency cost - A higher incongruency cost indicates that the subjects takes longer to process conflicting information. 2-Paired associated learning (PAL)- visual memory and new learning, PAL Number of Patterns Reached (0-8), PAL Total Errors (Adjusted) (0-64), PAL Total Attempts(0-64).

Time frame: at baseline, 3 months

MRI Imaging

At each of the evaluations, patients will undergo structural and functional MRI scanning. Images will be acquired on Vida 3 Tesla Scanner, configured with a 64-channel receiver head coils (Siemens Healthcare, Erlangen, Germany) at Shamir medical center radiology department.

Time frame: Change from Baseline immediately after the intervention

fMRI Imaging

Resting state fMRI(rsfMRI or R-fMRI)- a method of functional brain imaging that can be used to evaluate regional interactions that occur when a subject is not performing an explicit task. This resting brain activity is observed through changes in blood flow in the brain which creates what is referred to as a blood-oxygen-level dependent (BOLD) signal that can be measured using functional Magnetic Resonance Imaging (fMRI).

Time frame: Change from Baseline immediately after the intervention

Physical, Neurological and functional evaluation

A general physical and neurological evaluation will be done. NIHSS - The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS), will be used as part of the neurological evaluation to objectively quantify the impairment caused by the stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4 .For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment.

Time frame: Change from Baseline immediately after the intervention

electrical brain activity

Quantitative EEG (qEEG) including task related EEG analysis. EEG analysis for each state within subject and between subjects will include frequency analysis (peak frequency and relative power), oscillations (proportions of the different bands alpha, beta, theta, delta activities) and power spectra distribution.

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 1

blood tests will include Inflammatory markers: IL-1 (IL-1β): pg/mL

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 2

blood tests will include Inflammatory markers: IL-6: pg/mL

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 3

blood tests will include Inflammatory markers: Tumor necrosis factor-alpha (TNF-α): pg/mL

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 4

blood tests will include Inflammatory markers: hsCRP (high-sensitivity C-reactive protein): mg/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 5

blood tests will include Inflammatory markers: Exosomes: particles/mL (by NTA) or µg protein/mL (by protein assay)

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 6

blood tests will include Inflammatory markers: Serum VEGF: pg/mL

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 7

blood tests will include Inflammatory markers: Testosterone (serum): ng/dL or nmol/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 8

blood tests will include Inflammatory markers: Estradiol (E2, serum): pg/mL or pmol/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 9

blood tests will include Inflammatory markers: DHEA-S (serum): µg/dL (commonly) or µmol/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 10

blood tests will include Inflammatory markers: Progesterone (serum): ng/mL or nmol/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 11

blood tests will include Inflammatory markers: Cortisol (serum): µg/dL or nmol/L

Time frame: Change from Baseline immediately after the intervention

Inflammatory cytokines 12

blood tests will include Inflammatory markers: Telomere length: kilobases (kb) or relative T/S ratio (qPCR, arbitrary units)

Time frame: Change from Baseline immediately after the intervention