Physiological Effects of N-Acetyl Cysteine in Patients With Multiple Sclerosis (MSNAC)

March 25, 2024 updated by: Andrew Newberg, Thomas Jefferson University

Multiple Sclerosis (MS) is a disease in which the myelin surrounding the nerve cells is damaged which affects functioning. MS usually is treated with medications designed to reduce the occurrence of future MS events. Evidence suggests that an important part of the disease process is damage to the myelin and brain caused by too much oxygen (sometimes called oxidative stress) or too much inflammation (or swelling).

The overall goal of this study will be to determine whether N-acetyl cysteine (NAC) will help to support cerebral function in patients with Multiple Sclerosis (MS). This positron emission tomography magnetic resonance imaging (PET-MRI) study will utilize 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose positron emission tomography FDG PET to measure cerebral metabolism, along with MRI analysis, to measure metabolism and structural effects of NAC in patients with MS.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Detailed Description

The original protocol consisted of two arms. The first arm of this study will receive intravenous and oral NAC, a strong antioxidant that increases brain glutathione. NAC, is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. It is a common over-the-counter supplement that is also available as an injectable pharmaceutical that protects the liver in cases of acetaminophen overdose. Laboratory studies have displayed some benefits to use of NAC. It has the potential to reduce markers of oxidative damage, protect against cell death, and to increase glutathione in blood, which might be useful in preventing oxidative damage in MS patients. The second arm will be a waitlist control receiving standard MS care. It should be noted that both arms will receive standard of care treatment for MS while enrolled in the study.

We amended this protocol to increase the enrollment with an additional 30 participants: 15 in a waitlist group and 15 will receive NAC. Subjects be randomized to either receive NAC or be placed in a waitlist control group. Those patients receiving NAC would receive a combination of IV and oral NAC for 4 months. We may obtain NAC serum measures that require a blood draw at three time points, one at scanning before receiving any NAC, one after the first infusion dose of NAC before the second dose, and another one at the last scan and the last dose of NAC.

Study Type

Interventional

Enrollment (Estimated)

55

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinical diagnosis of relapsing remitting MS or progressive MS who do not plan to start a medication during the study, or on stable disease modifying medication (interferon, glatiramer, dimethyl fumarate, teriflunomide).
  • Age 18 years old to no upper limit
  • Physically independent, ambulatory
  • Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the period of pilot study. In addition, male subjects who have a partner of childbearing age should practice effective contraception.
  • Participants must be able to complete study procedures in the greater Philadelphia area.

Exclusion Criteria:

  • Patients are excluded who have received treatment with intravenous steroids within the past 90 days for reasons other than MS
  • Previous brain surgery that would interfere with determination of cerebral metabolism or structure on the FDG PET-MRI.
  • Score on Mini-Mental Status examination of 20 or lower.
  • Wheelchair-bound or bed-ridden, non-ambulatory.
  • Intracranial abnormalities that may complicate interpretation of the brain scans (e.g., stroke, tumor, vascular abnormality affecting the target area).
  • History of head trauma with loss of consciousness > 48 hours.
  • History of asthma requiring daily medications for adequate management.
  • Any medical disorder or physical condition that could reasonably be expected to interfere with the assessment of MS symptoms, or with any of the study assessments including the PET-MRI imaging.
  • Patients with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
  • Patients with current alcohol or drug abuse
  • Pregnant or lactating women.
  • Enrollment in active clinical trial/ experimental therapy within the prior 30 days.
  • Pending surgery during the course of the study.
  • Patients taking medications that might interact with NAC involved in this study will be evaluated on a case by case basis by the PI or study physician. These medications include: Medications for high blood pressure; Medications that slow blood clotting; Medications for diabetes; Nitroglycerin.
  • Patients with history of pulmonary hypertension.
  • Any neurological, psychiatric, or medical condition that might affect the distribution of the radiopharmaceutical in the body or brain (as determined by Investigator)
  • Currently using medications that might alter the distribution of radiopharmaceuticals in - -the body or brain (as determined by Investigator)
  • Patient exceeds the weight limit of the table
  • Claustrophobia that would prevent completion of imaging studies
  • Glucose level that would interfere with the FDG PET scan
  • Any additional contraindications for MRI; Has metallic objects (e.g., pacemakers) in the body

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: N-acetyl Cysteine Cohort
Intravenous N-acetyl Cysteine - 50mg in 200ml of D5W over one hour 1 x per week Oral N-acetyl Cysteine - 1 500mg tablet 2 x per day (on days IV N-acetyl cysteine is not administered)
Dietary supplement: N-acetyl Cysteine
The study consists of two arms. The first arm of this study will receive intravenous and oral NAC, a strong antioxidant that increases brain glutathione, which may be beneficial in MS. NAC, is the N-acetyl derivative of the naturally occurring amino acid, L-cysteine. It is a common over-the-counter supplement that is also available as an injectable pharmaceutical that protects the liver in cases of acetaminophen overdose. It has the potential to reduce markers of oxidative damage, protect against cell death, and to increase glutathione in blood, which might be useful in preventing oxidative damage in MS patients. The second arm will be a waitlist control receiving standard MS care. It should be noted that both arms will receive standard of care while enrolled into the study.
No Intervention: Control Cohort
Standard of Care Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the metabolic activity in the brain, and improved parameters with regard to the inflammation associated with the active lesions based on both MRI and PET findings.
Time Frame: Baseline and 60 ± 30 days
The goal would be to find a shorter duration of active lesions, reduced impact of the lesions on metabolic activity in the brain, and improved parameters with regard to the inflammation associated with the active lesions based on both MRI and PET findings. Changes on the PET and MRI scans would be correlated with changes in clinical findings and quality of life measures.
Baseline and 60 ± 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mini-Mental Status examination (MMSE)
Time Frame: Determine eligibility
Questionnaire used to determine eligibility and cognitive function. (exclusion from study if score is 20 or lower)
Determine eligibility
Multiple Sclerosis Quality of Life Inventory (MSQLI)
Time Frame: Baseline and 60 ± 30 days
Participants in the intervention and waitlist (standard of care) group will be asked to complete the full MSQLI which includes the following 10 scales - SF-36, MFIS, PES, BLCS, BWCS, IVIS, PDQ, MHI, MSSS, and SSS-W. The scales will be conducted at baseline and 60 ± 30 days concurrent to baseline and post scans.
Baseline and 60 ± 30 days
Health Status Questionnaire (SF-36) standard form
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Modified Fatigue Impact Scale (MFIS) standard form
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
MOS Pain Effects Scale (PES)
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Bladder Control Scale (BLCS)
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Bowel Control Scale (BWCS)
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Impact of Visual Impairment Scale (IVIS)
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Perceived Deficits Questionnaire (PDQ) standard form
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Mental Health Inventory (MHI) standard form
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
MOS Modified Social Support Survey (MSSS) standard form
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Sexual Satisfaction Scale (SSS)
Time Frame: Baseline and 60 ± 30 days
Questionnaire from Multiple Sclerosis Quality of Life Inventory that evaluates the quality of life for those diagnosed with Multiple Sclerosis (MS). Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days
Kurtzke Expanded Disability Status Scale (EDSS)
Time Frame: Baseline and 60 ± 30 days
Used to measure neurological impairment in those diagnosed with Multiple Sclerosis on a scale of 0 to 10. Will be used to determine improvements in MS symptoms.
Baseline and 60 ± 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Thomas Jefferson University

Investigators

  • Principal Investigator: Daniel A Monti, MD, MBA, Thomas Jefferson University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 5, 2017

Primary Completion (Estimated)

January 5, 2025

Study Completion (Estimated)

January 5, 2025

Study Registration Dates

First Submitted

January 19, 2017

First Submitted That Met QC Criteria

January 23, 2017

First Posted (Estimated)

January 26, 2017

Study Record Updates

Last Update Posted (Actual)

March 26, 2024

Last Update Submitted That Met QC Criteria

March 25, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16D.672

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Multiple Sclerosis

Clinical Trials on N-acetyl Cysteine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Madagascar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe