Chronic Fatigue SyndromePhase 2NAC ME/CFSNCT04542161
Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
A Phase 2 study testing NAC 900mg/day and NAC 3600mg/day in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Weill Medical College of Cornell University at 1 site in United States.
Trial summary
Chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS) is an unexplained multisymptom/multisystem disorder for which there are currently no validated treatments. The present exploratory clinical trial aims to advance our understand of the mechanisms of in situ GSH synthesis control through assessment of the… Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
- What is being tested?
- NAC 900mg/day and NAC 3600mg/day
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 30 Apr 2027
- Phase
- Phase 2
- 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 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males or females, ages 21 to 60 years (inclusive).
- Baseline GSH levels at or less than a predefined cutoff value.
- Primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
- Willing and capable of providing informed consent.
Who cannot join
- Significant and/or comorbid axis I (especially mood and anxiety) and axis II disorders.
- Any significant neurological illness or impairment.
- Other unstable medical conditions (asthma, hypertension, endocrine or metabolic disease, etc).
- History alcohol abuse.
- Positive urine toxicology at screening and on days of assessments.
- Positive pregnancy test at screening or on days of assessments.
- Contra-indication for clinical MRI scan (e.g., pacemaker, metallic prosthesis).
- Baseline GSH levels higher than a predefined cutoff value.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mechanistic Assessment of N-Acetylcysteine as an Antioxidant Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Through Dose Response and Treatment Target Engagement
Chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS) is an unexplained multisymptom/multisystem disorder for which there are currently no validated treatments. The present exploratory clinical trial aims to advance our understand of the mechanisms of in situ GSH synthesis control through assessment of the response of brain GSH and plasma markers of oxidative stress to different doses of NAC in comparison to placebo, as a potential treatment for ME/CFS that would provide neuroprotection against oxidative stress by restoring cortical GSH reserves. If successful, this exploratory clinical trial would address a significant public health concern by shedding new light onto the mechanisms of action of NAC in brain GSH restoration, which could open a new avenue for the development of potentially effective treatments for a disorder, ME/CFS, that currently has none.
Read the detailed description
This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC dosing on brain GSH levels and measure temporally concordant plasma levels of several established circulating markers of oxidative stress. Three study groups, of 20 subjects each (for a total of 60 who completed all components of the study), will each be administered a different dose (0 mg/day, 900mg/day, 3600mg/day) of the study intervention over a four week period; N-acetylcysteine (NAC) treatment. Subjects receiving 0 mg/day dose will be administered a placebo. Baseline visit assessments will include blood collection, survey questionnaires, MRI and MRS imaging. Subjects whose initial screening confirms low GSH level at baseline will be provided with a 4-week supplement of anonymized NAC or placebo caplets. After 4 weeks, subjects will then undergo a follow-up visit to repeat the baseline assessments.
- Being tested
- NAC 900mg/day, NAC 3600mg/day, NAC 0mg/day (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.
NAC 900mg/dayDrug
self administer NAC 900mg/day caplets for a four week period
NAC 3600mg/dayDrug
self administer NAC 3600mg/day caplets for a four week period
NAC 0mg/day (Placebo)Drug
self administer NAC 0mg/day (placebo) caplets for a four week period
| Study group | Role | What they receive |
|---|---|---|
| NAC 900mg/day | Active comparator | Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 900mg/day caplets for a four week period Receives: Drug: NAC 900mg/day |
| NAC 3600mg/day | Active comparator | Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 3600mg/day caplets for a four week period Receives: Drug: NAC 3600mg/day |
| NAC 0mg/day (Placebo) | Placebo comparator | Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 0mg/day (placebo) caplets for a four week period Receives: Drug: NAC 0mg/day (Placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in GSH levels of treatment response: measure 1
Levels of occipital cortex GSH, as measured in vivo with 1H MRS
Measured: pre/post 4 weeks of NAC supplementation
Change in GSH levels of treatment response: measure 2
Levels of striatal GSH, as measured in vivo with 1H MRS
Measured: pre/post 4 weeks of NAC supplementation
Secondary outcomes (8)
Change of levels of ventricular CSF lactate of treatment response
Levels of ventricular CSF lactate, as measured in vivo with 1H MRS
Measured: pre/post 4 weeks of NAC supplementation
Change of regional cerebral blood flow (rCBF) of treatment response
Regional cerebral blood flow (rCBF), as measured in vivo with perfusion MRI
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 1
Level of F2-isoprostanes, a marker of oxidative stress, in plasma samples obtained
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 2
Level of 8-hydroxy-2-deoxy guanosine (8-OH-2dG), a DNA damage marker, in plasma samples obtained
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 3
Level of reduced (GSH) glutathione, an antioxidant capacity and redox state marker, in plasma obtained
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 4
Level of oxidized (GSSG) glutathione, an antioxidant capacity and redox state marker, in plasma obtained
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 5
Level of GSH peroxidase, an antioxidant enzyme activity marker, in plasma obtained
Measured: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 6
Level of protein carbonyls, a protein damage marker, in plasma obtained
Measured: pre/post 4 weeks of NAC supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 Sep 2020
- Primary completion30 Apr 2027 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Fatigue SyndromeStudies of the same condition, open and under way.
- More trials run by Weill Medical College of Cornell UniversityThe 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 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 95 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Weill Medical College of Cornell University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dikoma C. Shungu, Ph.D., Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04542161
- Sponsor's protocol ID
- 20-01021280
- Other IDs
- R01NS116887
- Acronym
- NAC ME/CFS
- Status last verified
- Jun 2026
- First submitted
- 28 Aug 2020
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Assessment of N-Acetylcysteine as an Antioxidant Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Through Dose Response and Treatment Target Engagement
- ClinicalTrials.gov ID
- NCT04542161
- Acronym / sponsor ID
- NAC ME/CFS / 20-01021280
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 95 participants (estimated)
- Lead sponsor
- Weill Medical College of Cornell UniversityUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 30 Apr 2027 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 9 Sep 2020 (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.
Chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS) is an unexplained multisymptom/multisystem disorder for which there are currently no validated treatments. The present exploratory clinical trial aims to advance our understand of the mechanisms of in situ GSH synthesis control through assessment of the response of brain GSH and plasma markers of oxidative stress to different doses of NAC in comparison to placebo, as a potential treatment for ME/CFS that would provide neuroprotection against oxidative stress by restoring cortical GSH reserves. If successful, this exploratory clinical trial would address a significant public health concern by shedding new light onto the mechanisms of action of NAC in brain GSH restoration, which could open a new avenue for the development of potentially effective treatments for a disorder, ME/CFS, that currently has none.
Detailed description
This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC dosing on brain GSH levels and measure temporally concordant plasma levels of several established circulating markers of oxidative stress. Three study groups, of 20 subjects each (for a total of 60 who completed all components of the study), will each be administered a different dose (0 mg/day, 900mg/day, 3600mg/day) of the study intervention over a four week period; N-acetylcysteine (NAC) treatment. Subjects receiving 0 mg/day dose will be administered a placebo. Baseline visit assessments will include blood collection, survey questionnaires, MRI and MRS imaging. Subjects whose initial screening confirms low GSH level at baseline will be provided with a 4-week supplement of anonymized NAC or placebo caplets. After 4 weeks, subjects will then undergo a follow-up visit to repeat the baseline assessments.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| NAC 900mg/day | Active comparator | Drug: NAC 900mg/daySubjects who pass screening may be randomly assigned to this arm where they will self administer NAC 900mg/day caplets for a four week period |
| NAC 3600mg/day | Active comparator | Drug: NAC 3600mg/daySubjects who pass screening may be randomly assigned to this arm where they will self administer NAC 3600mg/day caplets for a four week period |
| NAC 0mg/day (Placebo) | Placebo comparator | Drug: NAC 0mg/day (Placebo)Subjects who pass screening may be randomly assigned to this arm where they will self administer NAC 0mg/day (placebo) caplets for a four week period |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Males or females, ages 21 to 60 years (inclusive).
- Baseline GSH levels at or less than a predefined cutoff value.
- Primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
- Willing and capable of providing informed consent.
Key exclusion criteria (8 listed)
- Significant and/or comorbid axis I (especially mood and anxiety) and axis II disorders.
- Any significant neurological illness or impairment.
- Other unstable medical conditions (asthma, hypertension, endocrine or metabolic disease, etc).
- History alcohol abuse.
- Positive urine toxicology at screening and on days of assessments.
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 |
|---|---|---|
| NAC 900mg/dayself administer NAC 900mg/day caplets for a four week period | Drug | NAC 900mg/day |
| NAC 3600mg/dayself administer NAC 3600mg/day caplets for a four week period | Drug | NAC 3600mg/day |
| NAC 0mg/day (Placebo)self administer NAC 0mg/day (placebo) caplets for a four week period | Drug | NAC 0mg/day (Placebo) |
Primary outcome
Change in GSH levels of treatment response: measure 1
Time frame: pre/post 4 weeks of NAC supplementation
Levels of occipital cortex GSH, as measured in vivo with 1H MRS
Change in GSH levels of treatment response: measure 2
Time frame: pre/post 4 weeks of NAC supplementation
Levels of striatal GSH, as measured in vivo with 1H MRS
8 secondary outcomes
Change of levels of ventricular CSF lactate of treatment response
Time frame: pre/post 4 weeks of NAC supplementation
Change of regional cerebral blood flow (rCBF) of treatment response
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 1
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 2
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 3
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 4
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 5
Time frame: pre/post 4 weeks of NAC supplementation
Change in Oxidative stress levels of treatment response: measure 6
Time frame: pre/post 4 weeks of NAC supplementation
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 Jun 2026.
- 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. This study is not recruiting at the moment.
Dikoma C. Shungu, Ph.D. principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NAC 900mg/day and NAC 3600mg/day in people with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, run by Weill Medical College of Cornell University at 1 site in United States.
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 4 inclusion and 8 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: under way, not looking for participants, as of the sponsor's last update on 22 Jun 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in GSH levels of treatment response: measure 1 (time frame: pre/post 4 weeks of NAC supplementation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jun 2026; AzTrials last refreshed its copy on 8 Nov 2026.