A pilot study of oxidative pathways in MS fatigue: randomized trial of N‐acetyl cysteine

Autor: Roland G. Henry, Yan Li, Bardia Nourbakhsh, Emmanuelle Waubant, Amit Akula, Nisha Revirajan, Antje Bischof, Kristen M. Krysko, Khang Nguyen, Michael Manguinao
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
medicine.medical_specialty
Pilot Projects
Neurosciences. Biological psychiatry. Neuropsychiatry
Placebo
Gastroenterology
law.invention
03 medical and health sciences
chemistry.chemical_compound
symbols.namesake
Route of administration
0302 clinical medicine
Double-Blind Method
Randomized controlled trial
law
Internal medicine
Outcome Assessment
Health Care
Humans
Medicine
RC346-429
Adverse effect
Research Articles
Fatigue
Fisher's exact test
Aged
business.industry
General Neuroscience
Free Radical Scavengers
Glutathione
Middle Aged
Multiple Sclerosis
Chronic Progressive
Acetylcysteine
Oxidative Stress
030104 developmental biology
chemistry
Tolerability
symbols
Feasibility Studies
Female
Neurology. Diseases of the nervous system
Neurology (clinical)
Sample collection
business
030217 neurology & neurosurgery
Research Article
RC321-571
Zdroj: Annals of Clinical and Translational Neurology, Vol 8, Iss 4, Pp 811-824 (2021)
Annals of Clinical and Translational Neurology
ISSN: 2328-9503
DOI: 10.1002/acn3.51325
Popis: Objective To assess feasibility, tolerability, and safety of N‐acetyl cysteine (NAC) for fatigue in progressive MS. Secondary objectives evaluated changes in fatigue and oxidative pathway biomarkers on NAC versus placebo. Methods Individuals with progressive MS with Modified Fatigue Impact Scale (MFIS) > t38 were randomized 2:1 to NAC 1250mg TID or placebo for 4 weeks. The primary outcome was tolerability and safety. The secondary outcome to evaluate efficacy was MFIS change from baseline to week 4 between groups. Exploratory biomarker outcomes included change in blood GSH/GSSG ratio (reduced‐to‐oxidized glutathione (GSH)) and in vivo relative GSH using 7T MR spectroscopy (MRS) between groups. Fisher exact test was used for categorical and rank sum for continuous outcomes. Results Fifiteen were randomized (10 NAC, 5 placebo; mean age 56.1 years, 80% female, median EDSS 6.0). At least one adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p = 0.75). There were two AEs attributed to NAC in one patient (abdominal pain and constipation), with 94% adherence to NAC. MFIS decreased in both groups at week 4, with the mean improvement of 11‐points on NAC versus 18‐points on placebo (p = 0.33). GSH/GSSG ratio decreased on placebo (−0.6) and NAC (−0.1) (p = 0.18). Change in GSH levels to total creatine in anterior and posterior cingulate cortex, insula, caudate, putamen, and thalamus did not differ between groups. Interpretation NAC was well‐tolerated in progressive MS, although reduction in fatigue on NAC was similar to placebo. Antioxidant blood and MRS biomarkers were not significantly altered by NAC, which could be due to dose, route of administration, time of sample collection, short half‐life, or lack of effect. Registered clinicaltrials.gov NCT02804594.
Databáze: OpenAIRE
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