Neuroprotection With N-acetyl Cysteine for Patients With Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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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.

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

Conditions
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Multiple Sclerosis, Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive

Intervention / Treatment
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* Drug: N-acetyl cysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |