Chronic Fatigue Syndrome, Myalgic Encephalomyelitis
Conditions
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.
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.
Interventions
DRUGNAC 900mg/day
self administer NAC 900mg/day caplets for a four week period
DRUGNAC 3600mg/day
self administer NAC 3600mg/day caplets for a four week period
self administer NAC 0mg/day (placebo) caplets for a four week period
Sponsors
Weill Medical College of Cornell University
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in GSH levels of treatment response: measure 1 | 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 | pre/post 4 weeks of NAC supplementation | Levels of striatal GSH, as measured in vivo with 1H MRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 1 | pre/post 4 weeks of NAC supplementation | Level of F2-isoprostanes, a marker of oxidative stress, in plasma samples obtained |
| 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 |
Countries
United States
Contacts
CONTACTXiangling Mao, MS
PRINCIPAL_INVESTIGATORDikoma C. Shungu, Ph.D.
Weill Medical College of Cornell University
Outcome results
None listed