Hyperbaric High Pressure Oxygen Therapy in Post-COVID Syndrome and ME/CFS

NCT ID: NCT06118138

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-07-15
• Study Completion Date: 2025-12-31

Brief Summary

The objective of this observational study is to document symptom progression in 60 patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) who undergo Hyperbaric Oxygen Therapy (HBOT) following COVID or other infections. Participants will receive HBOT treatment as an additional option after completing the Chronic Fatigue Syndrome CARE (CFS_CARE) study and will be invited to take part in this observational study. Patients will complete health evaluations in the form of questionnaires, including the 36-Item Short Form Health Survey (SF-36), to assess changes in ME/CFS-related symptoms after HBOT. Rather than evaluating the efficacy of HBOT itself, the study will focus on observing and documenting these changes. Its goal is to offer valuable insights into symptom progression in ME/CFS patients receiving HBOT, which can serve as a foundation for future interventional randomized controlled trials.

Detailed Description

Following mild to moderate COVID infection, around 10% of individuals develop post-COVID syndrome (PCS) characterized by symptoms like fatigue, exercise intolerance, cognitive impairment, headaches, and muscle pain (Kedor et al., 2022). Some PCS patients may later be diagnosed with ME/CFS, a severe and chronic disease triggered by infections (Renz-Polster & Scheibenbogen, 2022). ME/CFS presents symptoms such as debilitating fatigue, exercise intolerance, post-exertional malaise (PEM), headaches, muscle pain, cognitive impairment ("brain fog"), orthostatic intolerance, autonomic dysfunction, sleep disturbances, and a general feeling of illness. Currently, no curative therapy for ME/CFS exists. Therapeutic procedures for ME/CFS mainly focus on symptom management, but evidence-based and standardized treatments are urgently needed due to the high number of patients and the impact on healthcare (Renz-Polster & Scheibenbogen, 2022). Off-label drug and non-drug approaches are used, but their effectiveness lacks sufficient evidence from controlled trials.

ME/CFS and PCS may have different underlying pathomechanisms, with some patients showing endothelial dysfunction and reduced blood flow (Haffke et al., 2022). Enhancing blood flow and promoting the formation of new capillaries is a potential therapeutic approach due to the presumed role of reduced blood flow. In this regard, Hyperbaric Oxygen Therapy (HBOT) is under investigation as a treatment for ME/CFS and PCS, showing promising results in trials (e.g., Zilberman-Itskovich et al., 2022; Robbins et al., 2021; Kjiellberg et al., 2022; Akarsu et al., 2013). This non-interventional observational study aims to document symptom progression in 60 patients with ME/CFS who underwent HBOT following COVID or other infections. The study does not focus on evaluating the efficacy of HBOT itself.

ME/CFS patients currently participating in the Chronic Fatigue Syndrome CARE (CFS_CARE) study at Klinik Bavaria in Kreischa will have the opportunity to receive HBOT treatment as a supplementary offer from the clinic upon completion of the CFS_CARE study. Additionally, these patients will be invited to participate in this observational study during the final CFS_CARE presentation at the 12-month mark. HBOT is performed as part of the Conformité Européenne (CE) certificate, as an outpatient procedure within standard clinical practice, and independent of the study focus. Throughout the HBOT treatment, patients will undergo health assessments and symptom evaluations four weeks after treatment initiation and four weeks after completing the HBOT sessions. To facilitate this, patients will receive a link to a RedCap file containing questionnaires, including those previously utilized in the CFS_CARE study (36-Item Short Form Health Survey (SF-36), Munich Berlin Symptom Questionnaire (MBSQ), Chalder Fatigue Questionnaire, Bell Score). Completing the questionnaires typically requires approximately 45 minutes. The questionnaires will be collected every two months over 12 months, resulting in a total follow-up period of 10 months. A follow-up visit at the outpatient clinic is scheduled for four weeks after HBOT is completed.

The study's primary endpoint is to identify improvements in physical function following HBOT. This will be achieved by utilizing the SF-36 Physical Function (PF) questionnaire, which commonly serves as the primary endpoint in clinical trials focused on ME/CFS. It has been shown that an increase of at least 10 points in the SF-36 PF (range 0 - 100 = healthy) defines clinically relevant improvement ("a little better"), and an increase of 20 points defines greater clinical improvement ("much better") (Brigden 2018). Therefore, an increase of at least 10 points 4 weeks after HBOT is defined as a response and assessed as the primary endpoint.

The study-related measures do not pose significant risks or additional burdens to participants aside from the time required to complete the questionnaires. However, it has the potential to generate valuable knowledge regarding HBOT as a potential treatment for ME/CFS. To date, there has been no documentation of the efficacy of HBOT in ME/CFS through a clinical trial employing objective methods. The results of this observational study are expected to serve as the foundation for a potential interventional randomized controlled trial (RCT).

Conditions

Post-COVID ME/CFS

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Hyperbaric oxygen therapy (HBOT)

HBOT is a medical treatment employed for various conditions. It entails breathing 100% oxygen within a pressurized chamber known as a hyperbaric chamber. This oxygen-rich environment promotes healing and aids in combating specific infections.

In this study, the investigators will administer HBOT using a hyperbaric chamber set to 2 times the normal atmospheric pressure, indicated as 2 atmosphere absolute (ATA). This pressure surge enhances oxygen dissolution into the bloodstream, surpassing levels achievable at sea level. The pressure will be raised incrementally, followed by HBOT sessions lasting for a total of 90 minutes. The 90-minute sessions include brief 5-minute intervals for ambient air every 20 minutes to ensure safety and comfort. Treatment will be conducted five days a week over eight weeks.

Supervised by competent healthcare professionals, HBOT is considered safe, with potential side effects primarily stemming from heightened pressure and, in rare cases, oxygen toxicity.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Participants between the ages of 18 and 65 years who have previously participated in the CFS_CARE study and have been diagnosed with ME/CFS
• ME/CFS diagnosis based on the Canadian Consensus Criteria (CCC), characterized by exercise intolerance and symptom worsening lasting for a minimum of 14 hours
• Disease severity determined by a Bell Score ranging from 30 to 70
• Plan to undergo 20 or 40 days of Hyperbaric Oxygen Therapy (HBOT)
• Consent provided by the patient

Exclusion Criteria

• Unwillingness to consent to the storage of pseudonymized clinical data as a part of the study
• Pregnancy
• Presence of medical conditions that could potentially pose a risk during Hyperbaric Oxygen Therapy (HBOT) (e.g., heart failure, pulmonary disease, major depression, panic attacks)
• Acute infection (e.g., COVID, HIV, or hepatitis)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

KLINIK BAVARIA Kreischa

UNKNOWN

Sponsor Role: collaborator

Vivantes Klinikum im Friedrichshain

UNKNOWN

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: lead

Responsible Party

Carmen Scheibenbogen

Director of the Institute for Medical Immunology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carmen Scheibenbogen, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Locations

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Carmen Scheibenbogen, Prof. Dr.

Role: CONTACT

fatigue-centrum@charite.de

+49 (0)30 450 ext. 524103

Laura Kim

Role: CONTACT

laura.kim@charite.de

Facility Contacts

Carmen Scheibenbogen, Prof. Dr.

Role: primary

fatigue-centrum@charite.de

+49 30 450 ext. 524103

Laura Kim

Role: backup

laura.kim@charite.de

References

Kedor C, Freitag H, Meyer-Arndt L, Wittke K, Hanitsch LG, Zoller T, Steinbeis F, Haffke M, Rudolf G, Heidecker B, Bobbert T, Spranger J, Volk HD, Skurk C, Konietschke F, Paul F, Behrends U, Bellmann-Strobl J, Scheibenbogen C. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun. 2022 Aug 30;13(1):5104. doi: 10.1038/s41467-022-32507-6.

Reference Type: BACKGROUND

PMID: 36042189 (View on PubMed)

Renz-Polster H, Scheibenbogen C. [Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome]. Inn Med (Heidelb). 2022 Aug;63(8):830-839. doi: 10.1007/s00108-022-01369-x. Epub 2022 Jul 13. German.

Reference Type: BACKGROUND

PMID: 35925074 (View on PubMed)

Haffke M, Freitag H, Rudolf G, Seifert M, Doehner W, Scherbakov N, Hanitsch L, Wittke K, Bauer S, Konietschke F, Paul F, Bellmann-Strobl J, Kedor C, Scheibenbogen C, Sotzny F. Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME/CFS). J Transl Med. 2022 Mar 22;20(1):138. doi: 10.1186/s12967-022-03346-2.

Reference Type: BACKGROUND

PMID: 35317812 (View on PubMed)

Zilberman-Itskovich S, Catalogna M, Sasson E, Elman-Shina K, Hadanny A, Lang E, Finci S, Polak N, Fishlev G, Korin C, Shorer R, Parag Y, Sova M, Efrati S. Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial. Sci Rep. 2022 Jul 12;12(1):11252. doi: 10.1038/s41598-022-15565-0.

Reference Type: BACKGROUND

PMID: 35821512 (View on PubMed)

Robbins T, Gonevski M, Clark C, Baitule S, Sharma K, Magar A, Patel K, Sankar S, Kyrou I, Ali A, Randeva HS. Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention. Clin Med (Lond). 2021 Nov;21(6):e629-e632. doi: 10.7861/clinmed.2021-0462.

Reference Type: BACKGROUND

PMID: 34862223 (View on PubMed)

Kjellberg A, Abdel-Halim L, Hassler A, El Gharbi S, Al-Ezerjawi S, Bostrom E, Sundberg CJ, Pernow J, Medson K, Kowalski JH, Rodriguez-Wallberg KA, Zheng X, Catrina S, Runold M, Stahlberg M, Bruchfeld J, Nygren-Bonnier M, Lindholm P. Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial. BMJ Open. 2022 Nov 2;12(11):e061870. doi: 10.1136/bmjopen-2022-061870.

Reference Type: BACKGROUND

PMID: 36323462 (View on PubMed)

Akarsu S, Tekin L, Ay H, Carli AB, Tok F, Simsek K, Kiralp MZ. The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome. Undersea Hyperb Med. 2013 Mar-Apr;40(2):197-200.

Reference Type: BACKGROUND

PMID: 23682549 (View on PubMed)

Other Identifiers

01EP2201

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

HBOT

Identifier Type: -

Identifier Source: org_study_id