A Study of Oxidative Pathways in MS Fatigue
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
What it found
The main measure was safety, drug levels or similar, not whether the treatment works.
“At least one adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p = 0.75).”Read by software from the paper's abstract
4 weeks
| Group | n | Value |
|---|---|---|
| NAC 1250mg TID | 10 | At least one AE in 60% |
| Placebo | 5 | At least one AE in 80% |
p = 0.75
Read by software from the paper's abstract
What was tested
Treatment tested
- Acetylcysteine
Glutathione precursor|Mycolytic
Placebo
- Placebo
Results by group
Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine.
4 weeks
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| N-acetyl Cysteine | 12 adverse events | 10 | |
| Placebo | 6 adverse events | 5 |
N-acetyl Cysteine
Placebo
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| N-acetyl Cysteine | 10 | 0 (0.0%) | 0 |
| Placebo | 5 | 0 (0.0%) | 0 |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine.
4 weeks
Safety
Other measures (2)
Change in Fatigue Score on Questionnaires From Baseline
4 weeks
Thinking and memoryFatigueChange in Level of Blood Markers From Baseline
4 weeks
Fatigue
Who could take part
Progressive MS · 18 to 75 · EDSS 2.0 to 6.5
Show the full criteria
Inclusion criteria
1. Age 18 through 75 years included. 2. Ability to sign the informed consent before participation. 3. Females of childbearing age must have a negative pregnancy test at screening and use an effective method of contraception during the study participation period. 4. Diagnosis of primary or secondary progressive multiple sclerosis (according to the 2010 McDonald criteria). 5. Time since first reported MS symptoms more than one year. 6. EDSS score at the time of screening 2.0-6.5. 7. Fatigue reportedly present and screening MFIS more than 38 for patients who will be enrolled in the randomized placebo controlled part of the study. MFIS score of less than 38 is required for patients who are controls on the study.
Exclusion criteria
1. History of MS relapses in the previous 3 months. 2. Neurodegenerative progressive neurological disorders other than progressive MS. 3. Breastfeeding 4. History of bleeding disorders 5. Abnormal results of liver function test at screening (AST or ALT more than twice the upper limit of normal). 6. Receiving or about to start interferon beta or immunosuppressive medications (e.g. cyclophosphamide, mitoxantrone, methotrexate, mycophenolate mofetil) as these medication can be associated with fatigue. 7. Starting or changing the dose of other MS disease-modifying medications (including monoclonal antibodies such as rituximab, ocrelizumab, alemtuzumab, daclizumab) within 3 months of baseline visit. 8. No ongoing steroid treatment and no steroid treatment in the prior month. 9. Inability to undergo MRI scans (e.g. weight>350 pounds, severe claustrophobia, metal in the body). 10. Medical terminal conditions. 11. Currently treated for active malignancy or metastatic malignancy that has been treated in the past 1 year or undergoing extra screening for recurrence 12. Planned surgery within the following 12 weeks 13. Planning to move with the following next 12 weeks 14. Participating in another clinical trial with an experimental medication. 15. Alcohol or substance abuse, or any other condition that in the investigator's opinion would make the patient unsuitable for this study. 16. A history of allergic or anaphylactic reaction to NAC, or any component of the preparation. 17. Clinically unstable medical or psychiatric disorders that require acute treatment. 18. Active gastrointestinal ulcers. 19. Subjects taking concomitant medications or supplements known for their glutamatergic effects (e.g., dextromethorphan, D-cycloserine, memantine, lamotrigine, riluzole), antioxidant properties (DMG, TMG, other alternative treatments), or medications with an effect on sleepiness and possibly fatigue such as Provigil, Nuvigil and amantadine within 2 weeks of the baseline visit with the exception of short-term use of dextromethorphan as needed as a cough suppressant. Regular multivitamins will be allowed. 20. Patients taking anticoagulants 21. Patients with history of obvious secondary causes of fatigue, such as chronic insomnia, sleep apnea, narcolepsy, restless leg syndrome and significant bladder dysfunction disrupting sleep. 22. Screening Epworth Sleepiness Scale score greater than 15. 23. Starting or changing the dose of benzodiazepine, antidepressant, antipsychotics, anti-histamines, or stimulants within a month from the screening visit. 24. A score of 15 or greater on the Hospital Anxiety and Depression Scale (HADS) depression subscale. 25. Patients currently treated for asthma.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
This is a 4-week randomized, placebo-controlled, parallel group, double-blind, single center trial on effect of N-acetyl cysteine versus placebo on fatigue in patients with progressive MS defined by McDonald criteria. Subjects who enter the treatment phase of study, will be randomly assigned to either N-acetyl cysteine (1250 mg three times a day) or placebo (three times a day) for 4 weeks. There will be 3 in-person study visits (screening, baseline, and week 4) and 2 visits over the phone (week 2, and week 6 which is 2 weeks after completing last study drug dose). Visits will all occur in the morning to maximize consistency of assessments and evaluate main outcomes within 2 hours of morning dose of study medication. Fatigue questionnaires, and research samples will be obtained before neurological examination, or magnetic resonance imaging. Research blood draws will be obtained just after fatigue questionnaire completion. Brain spectroscopy will be obtained less than 2 hours after morning dose of study drug to maximize detection of the biological effect of study medication.
Papers
Results
A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine.Ann Clin Transl Neurol · 2021
At least one adverse event (AE) occurred in 60% on NAC versus 80% on placebo (p = 0.75).
Read by software from the paper's abstract
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History
Started
Oct 2016
Main results due
Jun 2018
Finished
Jun 2018
Results posted
Feb 2020