Abstract Details

Title N-acetyl cysteine for fatigue in progressive multiple sclerosis: A pilot randomized double-blind placebo-controlled trial

Topic Multiple Sclerosis

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-093

Objective To test the feasibility, tolerability and safety of N-acetyl cysteine (NAC) for fatigue in progressive MS. Secondary objectives included evaluating changes in fatigue and oxidative pathway biomarkers on NAC versus placebo.

Background Oxidative stress may contribute to MS fatigue, and antioxidant therapy may be beneficial.

Design/Methods Individuals with progressive MS with modified fatigue impact scale (MFIS) ≥38 were randomized 2:1 to NAC 1250 mg TID or placebo for 4 weeks. The primary efficacy endpoint was MFIS change from baseline to week 4 between groups. We also assessed week 4 to 6 MFIS change (2 weeks off study drug). Secondary biomarker endpoints included baseline to week 4 change in blood GSH/GSSG ratio (reduced to oxidized glutathione) and grey matter GSH concentration on 7T MR spectroscopy (MRS) between groups. Outcomes were collected within 2 hours of study drug administration. Fisher exact test was used for categorical and Wilcoxon rank-sum for continuous outcomes.

Results 15 individuals were randomly assigned (10 NAC, 5 placebo) from 2016-2018 (mean age 56.1 years, 80% female, mean disease duration 17.2 years, 67% primary and 33% secondary progressive MS, median EDSS 6). At least 1 adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p=0.75). MFIS decreased with treatment in both groups at week 4, with mean MFIS improvement of 23% on NAC versus 36% on placebo (p=0.33). This improvement was more sustained after discontinuation of NAC compared to placebo (NAC: 5% worsening versus placebo: 33% worsening week 4 to 6, p=0.18). GSH/GSSG ratio decreased more on placebo (27%) than NAC (3%) (p=0.18). Analysis of MRS data is ongoing.

Conclusions NAC was well tolerated in progressive MS, with suggestion for sustained fatigue improvement and a positive antioxidant biomarker effect. A larger trial with longer treatment is warranted to evaluate the efficacy of NAC for fatigue.

Authors/Disclosures
Kristen M. Krysko, MD (St. Michael's Hospital) PRESENTER	Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Krysko has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Krysko has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Krysko has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. The institution of Dr. Krysko has received research support from MS Society of Canda. The institution of Dr. Krysko has received research support from Roche.
Antje Bischof, MD	Dr. Bischof has nothing to disclose.
Bardia Nourbakhsh, MD (Johns Hopkins University)	Dr. Nourbakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics . Dr. Nourbakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alkermes. The institution of Dr. Nourbakhsh has received research support from Genentech. The institution of Dr. Nourbakhsh has received research support from National MS Society . The institution of Dr. Nourbakhsh has received research support from Department of Defense. The institution of Dr. Nourbakhsh has received research support from NIH. The institution of Dr. Nourbakhsh has received research support from Axsome Therapeutics. The institution of Dr. Nourbakhsh has received research support from TG Therapeutics .
Roland G. Henry, PhD (University of California, San Francisco)	Dr. Henry has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MEDDAY. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Henry has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Henry has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi/Genzyme.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Emmanuelle Waubant, MD, PhD, FAAN (USCF MS Center)	The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care.

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