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

NCT03032601 | Enrolling By Invitation

• 1 other identifier: 16D.672
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis

Keywords

MS (Multiple Sclerosis); Acute Fulminating; Sclerosis; 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose; 18F Fluorodeoxyglucose 2-Fluoro-2-deoxy-D-glucose (18 FDG); Fludeoxyglucose F 18; Fluorine-18-fluorodeoxyglucose; Positron Emission Tomography (PET); Magnetic Resonance Imaging (MRI); PET MRI; Acetylcysteine; N-acetyl cysteine (NAC); Oral supplements; functional magnetic resonance imaging (fMRI); FDG positron emission tomography (FDG PET)

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (13)

• Mini-Mental Status examination (MMSE)

  Determine eligibility

• Multiple Sclerosis Quality of Life Inventory (MSQLI)

  Baseline and 60 ± 30 days

• Health Status Questionnaire (SF-36) standard form

  Baseline and 60 ± 30 days

• Modified Fatigue Impact Scale (MFIS) standard form

  Baseline and 60 ± 30 days

• MOS Pain Effects Scale (PES)

  Baseline and 60 ± 30 days

Study Arms (2)

N-acetyl Cysteine Cohort

ACTIVE COMPARATOR

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

Control Cohort

NO INTERVENTION

Standard of Care Treatment

Interventions

N-acetyl Cysteine DIETARY_SUPPLEMENT

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.

N-acetyl Cysteine Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Shahrampour S, Heholt J, Wang A, Vedaei F, Mohamed FB, Alizadeh M, Wang Z, Zabrecky G, Wintering N, Bazzan AJ, Leist TP, Monti DA, Newberg AB. N-acetyl cysteine administration affects cerebral blood flow as measured by arterial spin labeling MRI in patients with multiple sclerosis. Heliyon. 2021 Jul 16;7(7):e07615. doi: 10.1016/j.heliyon.2021.e07615. eCollection 2021 Jul.

  PMID: 34377857 RESULT

MeSH Terms

Conditions

Multiple Sclerosis; Sclerosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Daniel A Monti, MD, MBA

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Integrative Medicine and Nutritional Sciences; Professor, Department of Radiology

Study Record Dates

• First Submitted: January 19, 2017
• First Posted: January 26, 2017
• Study Start: January 5, 2017
• Primary Completion (Estimated): July 8, 2027
• Study Completion (Estimated): July 8, 2027
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)