Hyperbaric Oxygen Therapy for Chronic Fatigue Syndrome (CFS)

Hyperbaric Oxygen Therapy for Chronic Fatigue Syndrome (CFS) - A Prospective, Randomized, Double-Blind, Sham-Controlled Study

This study evaluates the effects of hyperbaric oxygen therapy (HBOT) in patients with mild to moderate CFS/ME. Participants will undergo 60 HBOT sessions over 3 months with a 3-month follow-up, including physical, cognitive, imaging, and laboratory assessments.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Fatigue Syndrome
• Intervention / Treatment: Device: Hyperbaric oxygen therapy; Device: SHAM treatment

Detailed Description

Hyperbaric oxygen therapy (HBOT) for Chronic Fatigue Syndrome (CFS)/Myalgic Encephalomyelitis (ME) - The aim of the current study is to evaluate the effect of HBOT on patients suffering for mild to moderate CFS. Patients will undergo a series of 60 HBOT over a span of 3 months, with a 3 month follow-up period. Patient's evaluation point includes the following tests: physical performance, questionnaires, cognitive tests, brain MRI, EEG, blood tests & muscle biopsy.

• Study Type: Interventional
• Enrollment (Estimated): 74
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eli Kravchik, MD; Phone Number: 089779241; Email: elikr@shamir.gov.il
• Study Contact Backup: Name: Shai Efrati, Prof; Email: efratishai@outlook.com

Study Locations

• Israel
  • Zrifin, Israel, 70300
    • The Sagol Center for Hyperbaric Medicine and Research Shamir Medical Center (Assaf Harofeh)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject willing and able to read, understand and sign an informed consent
• Diagnosis of mild to moderate severity of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
• Patients diagnosed with CFS for more than 1 years
• Stable psychological and pharmacological treatment for more than three months prior to inclusion

Exclusion Criteria:

1. Inability to attend scheduled clinic visits and/or comply with the study protocol
2. Severe and very severe cases of ME/CFS
3. History or diagnosis of, brain tumors, brain surgery, epilepsy, neurodegenerative diseases
4. Active malignancy
5. Substance use at baseline, except for prescribed cannabis if vaporized or taken PO as tincture
6. Active smokers
7. Chronic heart failure with ejection fraction of 30 or less
8. Chest pathology incompatible with pressure changes (including active asthma or COPD)
9. Ear or Sinus pathology incompatible with pressure changes (above 3 otolaryngologist visits a year)
10. Pregnancy
11. An inability to perform an awake brain MRI
12. An inability to perform Neurotrax
13. Participation in another medical study
14. HBOT for any reason prior to study enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hyperbaric oxygen therapy; Hyperbaric Oxygen Therapy: 60 consecutive sessions, 5 sessions per week within a three months' period. Each session includes breathing 100% oxygen by mask at 2 ATA for 90 minutes with 5-minute air breaks every 20 minutes.	Device: Hyperbaric oxygen therapy; 60 consecutive sessions of breathing 100% oxygen by mask at 2 ATA for 90 minutes with 5-minute air breaks every 20 minutes, 5 sessions per week within a three months' period.
Sham Comparator: Sham Hyperbaric oxygen therapy; SHAM therapy: 60 consecutive sessions, 5 sessions per week within a three months' period. SHAM pressure will go up to 1.2 ATA during the first five minutes of the session (to simulate the pressure sensation in the ears), and then decrease during the next 5 minutes to 1.02 ATA for 90 minutes with 5-minute air breaks, every 20 minutes.	Device: SHAM treatment; 60 consecutive sessions of breathing 21% oxygen by mask at 1 ATA for 90 minutes with 5-minute air breaks every 20 minutes, 5 sessions per week within a three months' period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiopulmonary exercise test (CPET)	Physical performance evaluated by cardiopulmonary exercise test (CPET) on a bicycle or a treadmill. CPET will be used to determine the peak oxygen consumption (Peak VO2), first ventilatory threshold (VT1) and if possible, the second ventilatory threshold (VT2).	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DePaul Post-Exertional Malaise Questionnaire (DPEMQ)	A self-report instrument assessing the frequency and severity of post-exertional malaise symptoms in individuals with ME/CFS. Total scores typically range from the minimum value (no symptoms) to the maximum value (most severe and frequent symptoms), with higher scores indicating worse post-exertional malaise.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Short Form-36 Health Survey (SF-36)	A self-reported measure of health-related quality of life across eight domains. Each SF-36 scale is transformed to a 0 to 100 score, where 0 represents the worst health status and 100 represents the best health status. Higher scores indicate better health-related quality of life.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Pittsburgh Sleep Quality Index (PSQI)	a self-report questionnaire that assesses sleep quality and disturbances over the previous month. The measure consists of 19 individual items, creating 7 components that produce one global score. The score ranges from 0 to 21, with higher scores indicating poorer sleep quality.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Brief Symptom Inventory-18 (BSI-18)	The BSI-18 will be used to evaluate psychological distress. An 18 item self-report questionnaire which generates a 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). Higher scores indicate greater psychological distress.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Montreal Cognitive Assessment (MoCA)	A brief cognitive screening tool with high sensitivity and specificity for detecting mild cognitive impairment (MCI). The MoCA total score ranges from 0 to 30, with higher scores indicating better cognitive performance. A score of 26 or above is considered normal and a score lower than 26 is the cutoff point for diagnosis of cognitive impairment.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
NeuroTrax	NeuroTrax (NeuroTrax Corp., Houston, TX) is a computerized neurocognitive battery of tests used to assess brain wellness across multiple cognitive domains, including memory, executive function, visual spatial perception, verbal function, attention, information processing speed, and motor skills	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Brain MRI	Images will be acquired on MAGNETOM Vida 3T Scanner, T1-weighted images will be used for gray matter and hippocampal volumetric measurement. Statistical parametric mapping software SPM12, will be used for brain segmentation. Voxel-based morphometry (VBM) procedure to calculate the whole-brain volumes.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Brain EEG	Resting-state and task-related brain EEG measures. EEG will be recorded using a high-density dry-electrode system (115 channels, EEG-Sense, Israel). Recordings will include eyes-open rest (3 minutes), eyes-closed rest (3 minutes), and 20 minutes of cognitive tasks (N-Back, Stroop, Flanker, and multiple-object tracking). EEG data will undergo standard preprocessing (filtering, line-noise and artifact removal, and down-sampling). Primary EEG outcomes will include spectral measures (peak frequency and relative power; alpha, beta, theta, and delta band power), power spectral distribution, and functional connectivity indices. Event-related potentials will be extracted for the cognitive tasks, including event-related synchronization and desynchronization (ERS/ERD), with averages computed across artifact-free trials.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Sleep EEG	Physiological sleep EEG signals will be collected using a home wearable EEG headband (Muse S) paired with a mobile application. Multi-channel EEG will be recorded from frontal and temporal locations, together with inertial sensors to capture movement and head position. Primary sleep EEG outcomes will include validated sleep-wake classification and sleep staging metrics (percent time in light, deep, and REM sleep), sleep timing (bedtime, sleep onset, awakenings, final wake time), and sleep continuity indices (wake after sleep onset and sleep efficiency). Secondary analyses will include signal-level EEG features such as spectral power in conventional frequency bands and spindle-like activity. Higher sleep efficiency and higher proportions of deep (slow-wave) sleep will be interpreted as better sleep quality.	Baseline (3 consecutive nights within 2 weeks before treatment), post-treatment (3 consecutive nights within 21±7 days after last HBOT/Sham session), and at the end of the 3-month follow-up period (3 consecutive nights)
Orthostatic Intolerance - 10-min NASA Lean Test (NLT)	The 10-min NASA Lean Test (NLT) will be performed by asking the subject to lay supine for 10 min and then leaning against a wall for 10 min, while blood pressure and heart rate are measured	Baseline, monthly during treatment (3 months), at the post-treatment evaluation (within 21±7 days after last HBOT/Sham session), monthly during follow-up (3 months), at the end of the follow-up period (end of study evaluation).
Body Composition	Body composition will be assessed using the seca mBCA Ultra, a clinically validated segmental multi-frequency bioelectrical impedance analysis (SMF-BIA) system. The device estimates fat mass, fat-free mass, skeletal muscle mass, and total body water based on multi-frequency impedance measurements across body segments. Outcomes will include absolute values (kg or liters) and relative values (percentage of body weight) for each compartment. Higher fat mass and body fat percentage indicate greater adiposity, whereas higher fat-free mass and skeletal muscle mass indicate greater lean tissue.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Hand Grip test	Quick, non invasive assessment of the maximal force generated when squeezing a hand dynamometer. Reflecting strength of the hand and forearm muscles and serving as a proxy for overall muscle weakness, fatigability, and disease severity	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Peripheral blood biomarkers	Whole blood and plasma will be collected and stored for future biomarker analysis	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session, End of study evaluation: at the end of 3 month follow-up period
Muscle biopsy	A voluntary test. Participants will undergo a muscle biopsy using a 0.3mm Trucut needle in an aseptic technique. Muscle sample will be analysed using the Oxygraph (Oroboros Inc, Austria) for oxygen respiratory function, as well as staining for mitochondrial proteins and Mitochondrial DNA.	Baseline, post treatment evaluation within 21±7 days of last HBOT/Sham session.

Collaborators and Investigators

• Sponsor: Assaf-Harofeh Medical Center
• Investigators: Principal Investigator: Eli Kravchik, MD, principle investigator

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hyperbaric oxygen therapy; Myalgic Encephalomyelitis
• Additional Relevant MeSH Terms: Neuroinflammatory Diseases; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Pathologic Processes; Encephalomyelitis; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Pathological Conditions, Signs and Symptoms; Fatigue Syndrome, Chronic; Therapeutics; Respiratory Therapy; Oxygen Inhalation Therapy; Hyperbaric Oxygenation
• Other Study ID Numbers: 0015-26-ASF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No