Clinical trial NCT04542161: Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Fatigue Syndrome
Myalgic Encephalomyelitis
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2020-09-09
Enrollment: 95
Sex: ALL
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in GSH levels of treatment response: measure 1
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in GSH levels of treatment response: measure 2
timeFrame: pre/post 4 weeks of NAC supplementation
Secondary outcomes:
measure: Change of levels of ventricular CSF lactate of treatment response
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change of regional cerebral blood flow (rCBF) of treatment response
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 1
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 2
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 3
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 4
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 5
timeFrame: pre/post 4 weeks of NAC supplementation
measure: Change in Oxidative stress levels of treatment response: measure 6
timeFrame: pre/post 4 weeks of NAC supplementation
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Medical College of Cornell University
name: Dikoma C. Shungu, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: