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

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ClinicalTrials.gov Identifier: NCT04542161
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : June 9, 2021
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Weill Medical College of Cornell University

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
Chronic Fatigue Syndrome Myalgic Encephalomyelitis Drug: NAC 900mg/day Drug: NAC 3600mg/day Drug: NAC 0mg/day (Placebo) 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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
Actual Study Start Date : September 1, 2020
Estimated Primary Completion Date : April 30, 2025
Estimated Study Completion Date : April 30, 2025

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Change in GSH levels of treatment response [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Levels of striatal and occipital cortex GSH, as measured in vivo with 1H MRS,


Secondary Outcome Measures :
  1. Change in Oxidative stress levels of treatment response: measure 1 [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Level of F2-isoprostanes, a marker of oxidative stress, in plasma samples obtained

  2. Change of levels of ventricular CSF lactate of treatment response [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Levels of ventricular CSF lactate, as measured in vivo with 1H MRS,

  3. Change of regional cerebral blood flow (rCBF) of treatment response [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Regional cerebral blood flow (rCBF), as measured in vivo with perfusion MRI,

  4. Change in Oxidative stress levels of treatment response:measure 2 [ Time Frame: 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

  5. Change in Oxidative stress levels of treatment response:measure 3 [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Level of reduced (GSH) glutathione, an antioxidant capacity and redox state marker, in plasma obtained

  6. Change in Oxidative stress levels of treatment response:measure 4 [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Level of oxidized (GSSG) glutathione, an antioxidant capacity and redox state marker, in plasma obtained

  7. Change in Oxidative stress levels of treatment response:measure 5 [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Level of GSH peroxidase, an antioxidant enzyme activity marker, in plasma obtained

  8. Change in Oxidative stress levels of treatment response:measure 6 [ Time Frame: pre/post 4 weeks of NAC supplementation ]
    Level of protein carbonyls, a protein damage marker, in plasma obtained



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04542161


Contacts
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Contact: Jihyun Lee, MPH 2127462481 jil4015@med.cornell.edu
Contact: Xiangling Mao, MS 2127462632 xim2004@med.cornell.edu

Locations
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United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10021
Principal Investigator: Dikoma C. Shungu, Ph.D.         
Sub-Investigator: Xiangling Mao, MS         
Sub-Investigator: Elizabeth Sweeney, Ph.D.         
Sponsors and Collaborators
Weill Medical College of Cornell University
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Dikoma Shungu, Ph.D. Weill Medical College of Cornell University
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Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT04542161    
Other Study ID Numbers: 20-01021280
R01NS116887 ( U.S. NIH Grant/Contract )
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fatigue Syndrome, Chronic
Syndrome
Fatigue
Encephalomyelitis
Myalgia
Disease
Pathologic Processes
Virus Diseases
Infections
Muscular Diseases
Musculoskeletal Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuromuscular Diseases
Central Nervous System Infections
Musculoskeletal Pain
Pain
Neurologic Manifestations