Investigating the Effects of Intermittent Hypoxia-Hyperoxia Treatment (IHHT) in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) to Improve Fatigue, Pain, and Quality of Life by Targeting Mitochondrial Dysfunction and Autonomic Nervous System Impairment

Official title

REenergizeME: Oxygen Therapy (OT) as a Novel Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Overview

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

• Other Intermittent 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 mon
• Device Placebo
  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.

Primary outcome measures

• Change in SF-36 Vitality Domain score from baseline to post-treatment [Time frame: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up]

Secondary outcome measures (5)

• Change in health-related quality of life (SF-36 domains) [Time frame: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up]
• Change in fatigue severity (Fatigue Severity Scale, FSS) [Time frame: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up]
• Change in functional capacity (FUNCAP-27) [Time frame: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up]
• Change in autonomic symptoms (COMPASS-31) [Time frame: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up]
• Objective autonomic, neurophysiological, and functional performance measures [Time frame: Baseline and post-treatment (~8-10 weeks)]

Eligibility 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

Exclusion criteria

• Current or previous diagnosis of ME/CFS
• Participation in another clinical trial that may interfere with the present study
• Pregnancy, planned pregnancy, or breastfeeding
• Presence of clinically significant psychiatric, neurological, cardiovascular, pulmonary, metabolic, renal, hepatic, endocrine, or systemic disease
• Chronic pain conditions, migraine disorder, or recurrent headache/back pain likely to interfere with study assessments
• Obstructive lung disease
• Claustrophobia
• History of spontaneous pneumothorax
• Presence of implanted medical devices, prostheses, or other conditions considered incompatible with study procedures
• Current structured exercise programme or recent major change in exercise habits
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Denmark · 1 center

• Aarhus University — Aarhus

Identifiers

NCT: NCT07317401 · Sagsnr.: 2500959 · 10.46540/3165-00221B

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗