NAC ME/CFS: Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Study Details
Study Description
Brief 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 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: NAC 900mg/day 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 |
Drug: NAC 900mg/day
self administer NAC 900mg/day caplets for a four week period
|
| Active Comparator: NAC 3600mg/day 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 |
Drug: NAC 3600mg/day
self administer NAC 3600mg/day caplets for a four week period
|
| Placebo Comparator: 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 |
Drug: NAC 0mg/day (Placebo)
self administer NAC 0mg/day (placebo) caplets for a four week period
|
Outcome Measures
Primary Outcome Measures
- Change in GSH levels of treatment response [pre/post 4 weeks of NAC supplementation]
Levels of striatal and occipital cortex GSH, as measured in vivo with 1H MRS,
Secondary Outcome Measures
- Change in Oxidative stress levels of treatment response: measure 1 [pre/post 4 weeks of NAC supplementation]
Level of F2-isoprostanes, a marker of oxidative stress, in plasma samples obtained
- Change of levels of ventricular CSF lactate of treatment response [pre/post 4 weeks of NAC supplementation]
Levels of ventricular CSF lactate, as measured in vivo with 1H MRS,
- Change of regional cerebral blood flow (rCBF) of treatment response [pre/post 4 weeks of NAC supplementation]
Regional cerebral blood flow (rCBF), as measured in vivo with perfusion MRI,
- Change in Oxidative stress levels of treatment response:measure 2 [pre/post 4 weeks of NAC supplementation]
Level of 8-hydroxy-2-deoxy guanosine (8-OH-2dG), a DNA damage marker, in plasma samples obtained
- Change in Oxidative stress levels of treatment response:measure 3 [pre/post 4 weeks of NAC supplementation]
Level of reduced (GSH) glutathione, an antioxidant capacity and redox state marker, in plasma obtained
- Change in Oxidative stress levels of treatment response:measure 4 [pre/post 4 weeks of NAC supplementation]
Level of oxidized (GSSG) glutathione, an antioxidant capacity and redox state marker, in plasma obtained
- Change in Oxidative stress levels of treatment response:measure 5 [pre/post 4 weeks of NAC supplementation]
Level of GSH peroxidase, an antioxidant enzyme activity marker, in plasma obtained
- Change in Oxidative stress levels of treatment response:measure 6 [pre/post 4 weeks of NAC supplementation]
Level of protein carbonyls, a protein damage marker, in plasma obtained
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Males or females, ages 21 to 60 years (inclusive).
-
Baseline GSH levels at or less than a predefined cutoff value.
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Primary diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
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Willing and capable of providing informed consent.
Exclusion Criteria:
-
Significant and/or comorbid axis I (especially mood and anxiety) and axis II disorders.
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Any significant neurological illness or impairment.
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Other unstable medical conditions (asthma, hypertension, endocrine or metabolic disease, etc).
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History alcohol abuse.
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Positive urine toxicology at screening and on days of assessments.
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Positive pregnancy test at screening or on days of assessments.
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Contra-indication for clinical MRI scan (e.g., pacemaker, metallic prosthesis).
-
Baseline GSH levels higher than a predefined cutoff value.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Weill Cornell Medicine | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
- Principal Investigator: Dikoma C. Shungu, Ph.D., Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 20-01021280
- R01NS116887