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

Primary Purpose

Multiple Sclerosis

Status
Enrolling by invitation
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
N-acetyl Cysteine
Sponsored by
Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Multiple Sclerosis focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

N-acetyl Cysteine Cohort

Control Cohort

Arm Description

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)

Standard of Care Treatment

Outcomes

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.
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)
Questionnaire used to determine eligibility and cognitive function. (exclusion from study if score is 20 or lower)
Multiple Sclerosis Quality of Life Inventory (MSQLI)
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
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
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)
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)
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)
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)
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
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
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
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)
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)
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.

Full Information

First Posted
January 19, 2017
Last Updated
August 26, 2022
Sponsor
Thomas Jefferson University
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1. Study Identification

Unique Protocol Identification Number
NCT03032601
Brief Title
Physiological Effects of N-Acetyl Cysteine in Patients With Multiple Sclerosis
Acronym
MSNAC
Official Title
Physiological Effects of N-Acetyl Cysteine in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
January 5, 2017 (Actual)
Primary Completion Date
January 5, 2025 (Anticipated)
Study Completion Date
January 5, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Thomas Jefferson University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
N-acetyl Cysteine Cohort
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Control Cohort
Arm Type
No Intervention
Arm Description
Standard of Care Treatment
Intervention Type
Dietary Supplement
Intervention Name(s)
N-acetyl Cysteine
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
Baseline and 60 ± 30 days
Secondary Outcome Measure Information:
Title
Mini-Mental Status examination (MMSE)
Description
Questionnaire used to determine eligibility and cognitive function. (exclusion from study if score is 20 or lower)
Time Frame
Determine eligibility
Title
Multiple Sclerosis Quality of Life Inventory (MSQLI)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Health Status Questionnaire (SF-36) standard form
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Modified Fatigue Impact Scale (MFIS) standard form
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
MOS Pain Effects Scale (PES)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Bladder Control Scale (BLCS)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Bowel Control Scale (BWCS)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Impact of Visual Impairment Scale (IVIS)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Perceived Deficits Questionnaire (PDQ) standard form
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Mental Health Inventory (MHI) standard form
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
MOS Modified Social Support Survey (MSSS) standard form
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Sexual Satisfaction Scale (SSS)
Description
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.
Time Frame
Baseline and 60 ± 30 days
Title
Kurtzke Expanded Disability Status Scale (EDSS)
Description
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.
Time Frame
Baseline and 60 ± 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel A Monti, MD, MBA
Organizational Affiliation
Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to make individual participant data (IPD) available to other researchers.
Citations:
PubMed Identifier
34377857
Citation
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.
Results Reference
result

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

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