Neuroprotection With N-acetyl Cysteine for Patients With Progressive Multiple Sclerosis (NACPMS)

Randomized Controlled Trial of N-acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis

This study evaluates the effectiveness of N-acetyl cysteine (NAC) in the treatment of progressive multiple sclerosis. Half of the patients will receive NAC, while the other half will receive a placebo.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive
• Intervention / Treatment: Drug: N-acetyl cysteine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • University of California, San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• - 40-70 (inclusive) years in age,
• meet 2017 McDonald criteria (Thompson 2018),
• patients with primary or secondary progressive MS (Thompson 2018),
• at least 2 years since progressive symptom onset,
• evidence of clinical changes over the previous 2 years unrelated to relapses: increased EDSS or 20% slowing on 25-foot walk, change of ambulatory support, cognitive change documented on cognitive testing. Progression defined by patients in terms of ambulation perimeter or type of support to ambulate are acceptable if aforementioned physician-based measure changes are not available.
• EDSS score 3.0 to 7.0 (inclusive),
• can be on a stable disease-modifying treatment initiated > 3 months prior to screening,
• can be on stable doses of dalfampridine initiated at least one month before screening.

Exclusion Criteria:

• - MS relapses in the previous 6 months
• oral glucocorticosteroid treatment within the prior 3 months
• patient with issues undergoing MRI scans
• pregnancy or breastfeeding
• women of child-bearing potential not able to utilize an effective form of contraception for the duration of the study
• history of bleeding disorders
• active gastrointestinal ulcers
• abnormal liver function testing (aminotransferase (AST) or alanine aminotransferase (ALT) >2 times upper limit of normal)
• current treatment for active malignancy or metastatic malignancy treated in the past year
• alcohol or substance use disorder
• allergy to NAC
• planned surgery or move within 15 months
• use of medications/supplements with antioxidant properties (including over-the-counter NAC)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: N-acetyl cysteine; N-acetyl cysteine (NAC) 1200mg t.i.d.	Drug: N-acetyl cysteine; N-acetyl cysteine (NAC) is a Glutathione (GSH) precursor with antioxidant properties which make it relevant for neuroprotection.; Other Names: NAC
Placebo Comparator: Placebo; Placebo 1200mg t.i.d.	Drug: Placebo; Lactose Monohydrate, USP (100%), magnesium stearate, silicon dioxide NF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Number of adverse events recorded by system, severity, and by relationship to treatment arm.	15 months
Effect of NAC on on progression of brain, thalamic and cervical cord atrophy	The primary endpoint is brain, thalamic and cord atrophy measured by brain and cervical spine MRI at month 3 and month 15.	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical effects of NAC	Clinical effects in MS as measured by the 9-HPT, 25-foot walk, symbol digit modalities test (SDMT).	15 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of NAC on progression of MS	Monitoring progression using imaging metrics and changes captured by a wearable multi-sensor device.	15 months

Collaborators and Investigators

• Sponsor: Emmanuelle Waubant, MD PhD
• Collaborators: United States Department of Defense

Publications and helpful links

General Publications

• Schoeps VA, Graves JS, Stern WA, Zhang L, Nourbakhsh B, Mowry EM, Henry RG, Waubant E. N-Acetyl Cysteine as a Neuroprotective Agent in Progressive Multiple Sclerosis (NACPMS) trial: Study protocol for a randomized, double-blind, placebo-controlled add-on phase 2 trial. Contemp Clin Trials. 2022 Nov;122:106941. doi: 10.1016/j.cct.2022.106941. Epub 2022 Sep 28.

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Amino Acids; Cysteine; Amino Acids, Sulfur; Acetylcysteine
• Other Study ID Numbers: P0549747

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No