A Study of Oxidative Pathways in MS Fatigue

NCT02804594 | Completed Phase 2 Results DMC

• 1 other identifier: NAC Pilot
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Progressive Multiple Sclerosis; Fatigue

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine.

  Number of adverse events reported since baseline visit that are related to N-acetyl cysteine will be compared to the number of adverse events reported by participants in the placebo group.

  4 weeks

Secondary Outcomes (2)

• Change in Fatigue Score on Questionnaires From Baseline

  4 weeks

• Change in Level of Blood Markers From Baseline

  4 weeks

Other Outcomes (1)

• Changes in Metabolite Levels in Deep Grey Matter, and Surrounding White Matter on the Magnetic Resonance Images (MRI) From Baseline.

  4 weeks

Study Arms (2)

N-acetyl cysteine

ACTIVE COMPARATOR

1250 mg of N-acetyl cysteine three times daily

Drug: N-acetyl cysteine

Placebo

PLACEBO COMPARATOR

placebo three times daily

Drug: Placebo

Interventions

N-acetyl cysteine DRUG

1250 mg of N- acetyl cysteine taken three times daily

Also known as: NAC

N-acetyl cysteine

Placebo DRUG

placebo taken three times daily

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 through 75 years included.
• Ability to sign the informed consent before participation.
• Females of childbearing age must have a negative pregnancy test at screening and use an effective method of contraception during the study participation period.
• Diagnosis of primary or secondary progressive multiple sclerosis (according to the 2010 McDonald criteria).
• Time since first reported MS symptoms more than one year.
• EDSS score at the time of screening 2.0-6.5.
• 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.

You may not qualify if:

• History of MS relapses in the previous 3 months.
• Neurodegenerative progressive neurological disorders other than progressive MS.
• Breastfeeding
• History of bleeding disorders
• Abnormal results of liver function test at screening (AST or ALT more than twice the upper limit of normal).
• 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.
• 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.
• No ongoing steroid treatment and no steroid treatment in the prior month.
• Inability to undergo MRI scans (e.g. weight\>350 pounds, severe claustrophobia, metal in the body).
• Medical terminal conditions.
• Currently treated for active malignancy or metastatic malignancy that has been treated in the past 1 year or undergoing extra screening for recurrence
• Planned surgery within the following 12 weeks
• Planning to move with the following next 12 weeks
• Participating in another clinical trial with an experimental medication.
• Alcohol or substance abuse, or any other condition that in the investigator's opinion would make the patient unsuitable for this study.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (1)

• Krysko KM, Bischof A, Nourbakhsh B, Henry RG, Revirajan N, Manguinao M, Nguyen K, Akula A, Li Y, Waubant E. A pilot study of oxidative pathways in MS fatigue: randomized trial of N-acetyl cysteine. Ann Clin Transl Neurol. 2021 Apr;8(4):811-824. doi: 10.1002/acn3.51325. Epub 2021 Mar 6.

  PMID: 33675156 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Fatigue

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Emmanuelle Waubant, MD
• Organization: University of California San Francisco

Emmanuelle.Waubant@ucsf.edu

415 514 2468

Study Officials

• Emmanuelle Waubant, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2016
• First Posted: June 17, 2016
• Study Start: October 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: July 11, 2025
• Results First Posted: February 18, 2020

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)