Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3)
Conditions
Brief summary
This study is testing a new treatment for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and long-term symptoms after COVID-19. Both conditions cause extreme fatigue, muscle pain, "brain fog," and trouble concentrating, which often get worse after physical or mental activity. Currently, no effective treatments are available. The treatment being studied is called Intermittent Hypoxia-Hyperoxia Treatment (IHHT). It uses a machine called HypoxBreath to deliver short cycles of low oxygen (hypoxia) and high oxygen (hyperoxia) through a mask. Each session lasts 22-40 minutes and is carefully monitored to track oxygen levels, heart rate, and breathing. The therapy is customized for each patient to ensure comfort and effectiveness. IHHT is believed to help the body adapt to oxygen-related stress, improving energy production and reducing inflammation. In this trial, 104 patients with ME/CFS will be randomly assigned to receive either IHHT or a placebo treatment with normal oxygen levels over eight weeks. The placebo group will follow a similar procedure without oxygen changes. An additional 20 healthy individuals will be recruited as a comparison group, but they will not undergo the treatment. Participants will have medical check-ups before and after treatment to evaluate changes in fatigue, mental sharpness, pain, autonomic nervous system function, and overall quality of life. Blood samples and small skin biopsies will also be taken to study the biological processes behind ME/CFS and how the treatment works. This research aims to find out if IHHT can improve the lives of people with ME/CFS or long-term COVID symptoms. The results could also provide new insights into the causes of these challenging conditions and guide future treatments.
Interventions
OTHERIntermittent hypoxia-hyperoxia treatment (IHHT)
The apparatus used to deliver the IHHT is the HypoxBreath machine (TUR GmbH, Rostock, Germany, CE Medical device class IIa). The HypoxBreath machine is constructed with a built-in compressor, an air reservoir, and a set of membranes, making it possible for the machine to either add or remove oxygen from the atmospheric air, thus delivering a dynamic FiO2 (fraction of inspired oxygen). The individualized therapy settings are regulated via the attached user interface. It is connected to a desk monitor and a data-collecting server.
DEVICEPlacebo
The placebo group will undergo 'sham treatment' with air breathing at 21% FiO2. To equate the sensation of oxygen therapy, airbrakes will be simulated similar to the oxygen therapy intervals in the treatment protocol.
Sponsors
University of Aarhus
Independent Research Fund Denmark
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 59 Years
Healthy volunteers
Yes
Inclusion criteria
ME/CFS Patients Inclusion Criteria: * Female sex * Age 20-59 years * Established diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) according to the International Consensus Criteria (ICC) * Disease duration \>6 months * Presence of post-exertional malaise (PEM) * Mild or moderate disease severity according to NICE guidelines * Body mass index (BMI) \>18 and \<30 kg/m² * Ability and willingness to attend study visits and complete the intervention protocol * Provision of written informed consent * Willingness to comply with all study procedures and restrictions throughout the study period * Use of highly effective contraception during study participation for women of childbearing potential
Exclusion criteria
* Severe ME/CFS according to NICE guidelines * Participation in another clinical trial that may interfere with the present study * Pregnancy, planned pregnancy, or breastfeeding * Presence of clinically significant psychiatric disease not considered part of ME/CFS and likely to interfere with study participation or interpretation of results * Presence of clinically significant neurological disease, peripheral nerve disorder, or other neurological dysfunction not considered part of ME/CFS * Active internal disease or clinically significant cardiovascular, pulmonary, metabolic, renal, hepatic, endocrine, or systemic disease that may interfere with study participation or interpretation of outcomes * Obstructive lung disease * Claustrophobia * History of spontaneous pneumothorax * Presence of implanted medical devices, prostheses, or other conditions considered incompatible with IHHT * Chronic pain conditions not considered part of ME/CFS and likely to interfere with assessments * Current structured graded exercise therapy (GET) or structured exercise programme * Significant alcohol, tobacco, or cannabis use considered likely to interfere with study participation or interpretation of outcomes * Inability to comply with study procedures or communicate meaningfully with study personnel * Any condition which, in the opinion of the investigator, may compromise participant safety or study integrity Healthy Controls Inclusion Criteria: * Female sex * Age 20-59 years * Body mass index (BMI) \>18 and \<30 kg/m² * Ability and willingness to attend study visits * Provision of written informed consent * Good general health without clinically significant chronic medical, neurological, psychiatric, or pain conditions * Activity level and BMI broadly matched to ME/CFS participants * Willingness to comply with all study procedures and restrictions throughout the study period * Use of highly effective contraception during study participation for women of childbearing potential
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in SF-36 Vitality Domain score from baseline to post-treatment | Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up | Change in the vitality domain of the 36-Item Short Form Health Survey (SF-36), assessing fatigue and energy-related quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in health-related quality of life (SF-36 domains) | Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up | Assessment of additional SF-36 quality-of-life domains. |
| Change in fatigue severity (Fatigue Severity Scale, FSS) | Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up | Assessment of fatigue severity and functional impact using the Fatigue Severity Scale (FSS). |
| Change in functional capacity (FUNCAP-27) | Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up | Assessment of functional capacity using the FUNCAP-27 questionnaire. |
| Change in autonomic symptoms (COMPASS-31) | Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up | Assessment of autonomic symptom burden using the Composite Autonomic Symptom Score-31 (COMPASS-31). |
| Objective autonomic, neurophysiological, and functional performance measures | Baseline and post-treatment (~8-10 weeks) | Objective assessments of autonomic function, sudomotor function, neurophysiology, tissue oxygenation, cognitive performance, and physical performance. |
Countries
Denmark
Contacts
CONTACTRikke KJ Olsen
CONTACTMastaneh Nochi
Outcome results
None listed