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

Sponsor

Thomas Jefferson University (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT03032601

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Dietary Supplement: N-acetyl Cysteine	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

55 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Jan 5, 2017

Anticipated Primary Completion Date :

Jan 5, 2025

Anticipated Study Completion Date :

Jan 5, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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. [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.

Secondary Outcome Measures

Mini-Mental Status examination (MMSE) [Determine eligibility]
Questionnaire used to determine eligibility and cognitive function. (exclusion from study if score is 20 or lower)
Multiple Sclerosis Quality of Life Inventory (MSQLI) [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.
Health Status Questionnaire (SF-36) standard form [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.
Modified Fatigue Impact Scale (MFIS) standard form [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.
MOS Pain Effects Scale (PES) [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.
Bladder Control Scale (BLCS) [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.
Bowel Control Scale (BWCS) [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.
Impact of Visual Impairment Scale (IVIS) [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.
Perceived Deficits Questionnaire (PDQ) standard form [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.
Mental Health Inventory (MHI) standard form [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.
MOS Modified Social Support Survey (MSSS) standard form [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.
Sexual Satisfaction Scale (SSS) [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.
Kurtzke Expanded Disability Status Scale (EDSS) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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