Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (NAC ME/CFS)

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 2

Conditions: Myalgic Encephalomyelitis; Chronic Fatigue Syndrome

Treatments: Drug: NAC 3600mg/day; Drug: NAC 0mg/day (Placebo); Drug: NAC 900mg/day

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04542161

20-01021280

R01NS116887 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 95 estimated patients

Sex: All

Ages: 21 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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95 participants in 3 patient groups, including a placebo group

NAC 900mg/day

Active Comparator group

Description:

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

Treatment:

Drug: NAC 900mg/day

NAC 3600mg/day

Active Comparator group

Description:

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

Treatment:

Drug: NAC 3600mg/day

NAC 0mg/day (Placebo)

Placebo Comparator group

Description:

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

Treatment:

Drug: NAC 0mg/day (Placebo)