Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3)REenergizeMENCT07317401
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
A study testing Intermittent hypoxia-hyperoxia treatment (IHHT) in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3), run by University of Aarhus at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 59 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3)
- What is being tested?
- Intermittent hypoxia-hyperoxia treatment (IHHT)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Jun 2026to 1 Jan 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 59 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
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- 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
- 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
Who cannot join
- 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
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- 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
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site
Aarhus University
Aarhus, Region Midt, 8200
Rikke KJ Olsen, PhD, +4561262471, rikke.olsen@clin.au.dk
English
About this study
Official title: REenergizeME: Oxygen Therapy (OT) as a Novel Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
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.
Read more
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.
- Being tested
- Intermittent hypoxia-hyperoxia treatment (IHHT), Placebo
- Medical subject headings
- Fatigue Syndrome, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intermittent hypoxia-hyperoxia treatment (IHHT)Other
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.
PlaceboDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent hypoxia-hyperoxia treatment (IHHT) | Active comparator | An individualized treatment is administered to patients in 4-7 intervals, within 22-40 minutes. Blood oxygen saturation (O2-Sat) rises and falls cyclically, due to fluctuating fractions of inspired oxygen (FiO2): 9-13% in the hypoxic phase and 36% in the hyperoxic restitution phase. Receives: Other: Intermittent hypoxia-hyperoxia treatment (IHHT) |
| Sham treatment | Placebo comparator | The placebo group will undergo 'sham treatment' with air breathing at 21% FiO2. To equate the sensation of IHHT, airbrakes will be simulated similar to the IHHT intervals in the treatment protocol. Receives: Device: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in SF-36 Vitality Domain score from baseline to post-treatment
Change in the vitality domain of the 36-Item Short Form Health Survey (SF-36), assessing fatigue and energy-related quality of life.
Measured: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up
Secondary outcomes (5)
Change in health-related quality of life (SF-36 domains)
Assessment of additional SF-36 quality-of-life domains.
Measured: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up
Change in fatigue severity (Fatigue Severity Scale, FSS)
Assessment of fatigue severity and functional impact using the Fatigue Severity Scale (FSS).
Measured: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up
Change in functional capacity (FUNCAP-27)
Assessment of functional capacity using the FUNCAP-27 questionnaire.
Measured: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up
Change in autonomic symptoms (COMPASS-31)
Assessment of autonomic symptom burden using the Composite Autonomic Symptom Score-31 (COMPASS-31).
Measured: Baseline, post-treatment (~8-10 weeks), and 3-, 6-, and 12-month follow-up
Objective autonomic, neurophysiological, and functional performance measures
Objective assessments of autonomic function, sudomotor function, neurophysiology, tissue oxygenation, cognitive performance, and physical performance.
Measured: Baseline and post-treatment (~8-10 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3)Studies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Independent Research Fund Denmark
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07317401
- Sponsor's protocol ID
- Sagsnr.: 2500959
- Other IDs
- 10.46540/3165-00221B
- Acronym
- REenergizeME
- Status last verified
- Jan 2026
- First submitted
- 19 Dec 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nochi M, Kristensen SK, Mehrani N, Guerreiro I, Norholm IMD, Chandra S, Olufsen M, Gudbergsen LR, Brinth LS, Stokholm R, Karlsson P, Tankisi H, Mehlsen J, Foldager CB, Olsen RKJ. REenergizeME: intermittent hypoxia-hyperoxia treatment for myalgic encephalomyelitis/chronic fatigue syndrome-protocol for a randomised, placebo-controlled trial. BMJ Open. 2026 Aug 14;16(8):e117729. doi: 10.1136/bmjopen-2026-117729.
PubMed 42601095
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- REenergizeME: Oxygen Therapy (OT) as a Novel Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
- ClinicalTrials.gov ID
- NCT07317401
- Acronym / sponsor ID
- REenergizeME / Sagsnr.: 2500959
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Independent Research Fund Denmark
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Jun 2027 (estimated)
- Study completion
- 1 Jan 2029 (estimated)
- First posted
- 5 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intermittent hypoxia-hyperoxia treatment (IHHT) | Active comparator | Other: Intermittent hypoxia-hyperoxia treatment (IHHT)An individualized treatment is administered to patients in 4-7 intervals, within 22-40 minutes. Blood oxygen saturation (O2-Sat) rises and falls cyclically, due to fluctuating fractions of inspired oxygen (FiO2): 9-13% in the hypoxic phase and 36% in the hyperoxic restitution phase. |
| Sham treatment | Placebo comparator | Device: PlaceboThe placebo group will undergo 'sham treatment' with air breathing at 21% FiO2. To equate the sensation of IHHT, airbrakes will be simulated similar to the IHHT intervals in the treatment protocol. |
Who may qualify
- Ages
- 20 to 59 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (20 listed)
- 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)
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 monitor and a data-collecting server. | Other | Intermittent hypoxia-hyperoxia treatment (IHHT) |
| PlaceboThe 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. | Device | Sham treatment |
Primary outcome
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
Change in the vitality domain of the 36-Item Short Form Health Survey (SF-36), assessing fatigue and energy-related quality of life.
5 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Derived from this study: PubMed 42601095Nochi M, Kristensen SK, Mehrani N, Guerreiro I, Norholm IMD, Chandra S, Olufsen M, Gudbergsen LR, Brinth LS, Stokholm R, Karlsson P, Tankisi H, Mehlsen J, Foldager CB, Olsen RKJ. REenergizeME: intermittent hypoxia-hyperoxia treatment for myalgic encephalomyelitis/chronic fatigue syndrome-protocol for a randomised, placebo-controlled trial. BMJ Open. 2026 Aug 14;16(8):e117729. doi: 10.1136/bmjopen-2026-117729.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intermittent hypoxia-hyperoxia treatment (IHHT) in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) (ICD-10 G93.3), run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rikke KJ Olsen (+45 61262471, rikke.olsen@clin.au.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07317401, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.