A Study of Oxidative Pathways in MS Fatigue

• Status: Completed
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of California, San Francisco
• Treatments: Acetylcysteine; N-monoacetylcystine

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.