Evidence map›Paper›PMID 33675156›Full record

Trial reportAnnals of clinical and translational neurology2021

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

Kristen M Krysko, Antje Bischof, Bardia Nourbakhsh, Roland G Henry, Nisha Revirajan, Michael Manguinao, Khang Nguyen, Amit Akula, Yan Li, Emmanuelle Waubant

Registry-linked trialOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02804594 (A Phase 2 Randomized, Placebo- Controlled, Parallel Group, Double Blinded Single Center Study on Effect of N-acetyl Cysteine Compared to Placebo on Fatigue in Patients With Progressive Multiple Sclerosis), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02804594 phase2completednot on this map

A Phase 2 Randomized, Placebo- Controlled, Parallel Group, Double Blinded Single Center Study on Effect of N-acetyl Cysteine Compared to Placebo on Fatigue in Patients With Progressive Multiple Sclerosis

TypeinterventionalSponsorUniversity of California, San FranciscoRan2016 to 2018Enrolled15ConditionsProgressive Multiple Sclerosis, FatigueArmsN-acetyl cysteine, Placebo
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Neuroimaging at 7 Tesla: a pictorial narrative review.Quantitative imaging in medicine and surgery · 2022
    Review
  8. Review
  9. Article
  10. Antioxidants (Basel, Switzerland) · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Kristen M KryskoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0003-0090-597X
Antje BischofUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0003-3862-5738
Bardia NourbakhshDepartment of Neurology, Johns Hopkins University, Baltimore, Maryland, USA.ORCID 0000-0002-6617-2003
Roland G HenryUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Nisha RevirajanUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Michael ManguinaoUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Khang NguyenUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Amit AkulaUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Yan LiDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Emmanuelle WaubantUCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, California, USA.ORCID 0000-0001-5188-0157
University of California, San Francisco · USJohns Hopkins University · USSt. Michael's Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo 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.

methodsIndividuals 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.

resultsFifiteen 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.

interpretationNAC 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.

Indexed as

AcetylcysteineAdultAgedDouble-Blind MethodFatigueFeasibility StudiesFemaleFree Radical ScavengersHumansMaleMiddle AgedMultiple Sclerosis, Chronic ProgressiveOutcome Assessment, Health CareOxidative StressPilot ProjectsAcetylcysteineFree Radical Scavengers

Identifiers

PMID33675156
PMCPMC8045913
OpenAlexW3135819604

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.