Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Oxidative Pathways in MS Fatigue

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02804594
Recruitment Status : Completed
First Posted : June 17, 2016
Results First Posted : February 18, 2020
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This is a 4-week randomized, placebo-controlled, parallel group, double-blind, single center trial on effect of N-acetyl cysteine versus placebo on fatigue in patients with progressive MS defined by McDonald criteria. Subjects who enter the treatment phase of study, will be randomly assigned to either N-acetyl cysteine (1250 mg three times a day) or placebo (three times a day) for 4 weeks. There will be 3 in-person study visits (screening, baseline, and week 4) and 2 visits over the phone (week 2, and week 6 which is 2 weeks after completing last study drug dose). Visits will all occur in the morning to maximize consistency of assessments and evaluate main outcomes within 2 hours of morning dose of study medication. Fatigue questionnaires, and research samples will be obtained before neurological examination, or magnetic resonance imaging. Research blood draws will be obtained just after fatigue questionnaire completion. Brain spectroscopy will be obtained less than 2 hours after morning dose of study drug to maximize detection of the biological effect of study medication.

Condition or disease Intervention/treatment Phase
Progressive Multiple Sclerosis Fatigue Drug: N-acetyl cysteine Drug: Placebo Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Placebo- Controlled, Parallel Group, Double Blinded Single Center Study on Effect of N-acetyl Cysteine Compared to Placebo on Fatigue in Patients With Progressive Multiple Sclerosis
Actual Study Start Date : October 1, 2016
Actual Primary Completion Date : June 1, 2018
Actual Study Completion Date : June 1, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: N-acetyl cysteine
1250 mg of N-acetyl cysteine three times daily
Drug: N-acetyl cysteine
1250 mg of N- acetyl cysteine taken three times daily
Other Name: NAC

Placebo Comparator: Placebo
placebo three times daily
Drug: Placebo
placebo taken three times daily




Primary Outcome Measures :
  1. Number of Adverse Events Reported Since Baseline Visit That Are Related to N-acetyl Cysteine. [ Time Frame: 4 weeks ]
    Number of adverse events reported since baseline visit that are related to N-acetyl cysteine will be compared to the number of adverse events reported by participants in the placebo group.


Secondary Outcome Measures :
  1. Change in Fatigue Score on Questionnaires From Baseline [ Time Frame: 4 weeks ]
    Change in fatigue score on questionnaires from baseline visit to week-4 is calculated for the Modified Fatigue Impact Scale (MFIS) questionnaire. The MFIS is a self-report measure to rate fatigue in Multiple Sclerosis. The total score, ranging from 0 to 84 is the sum of three subscales (physical, cognitive, and psychosocial functioning). Higher numbers indicate greater fatigue. Modified fatigue Impact scale of more than 38 is one of the inclusion criteria for the study. Study participants who scored higher value on the questionnaire at week-4 are considered to have worsened fatigue from the baseline visit.

  2. Change in Level of Blood Markers From Baseline [ Time Frame: 4 weeks ]
    Baseline to week 4 change in blood GSH/GSSG ratio (wherein GSH is glutathione in reduced state and GSSG is glutathione in oxidized state) and grey matter GSH concentration on 7T MR spectroscopy (MRS) between groups. We hypothesize that fatigue is associated with the GSH/GSSG ratio.


Other Outcome Measures:
  1. Changes in Metabolite Levels in Deep Grey Matter, and Surrounding White Matter on the Magnetic Resonance Images (MRI) From Baseline. [ Time Frame: 4 weeks ]
    Conventional T2/ T1-weighted images will be obtained at baseline for all subjects enrolled in the treatment phase of the study. We will perform brain MRI on 7T machine, and the sequences will be collected at baseline, and week-4 visit.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 18 through 75 years included.
  2. Ability to sign the informed consent before participation.
  3. Females of childbearing age must have a negative pregnancy test at screening and use an effective method of contraception during the study participation period.
  4. Diagnosis of primary or secondary progressive multiple sclerosis (according to the 2010 McDonald criteria).
  5. Time since first reported MS symptoms more than one year.
  6. EDSS score at the time of screening 2.0-6.5.
  7. Fatigue reportedly present and screening MFIS more than 38 for patients who will be enrolled in the randomized placebo controlled part of the study. MFIS score of less than 38 is required for patients who are controls on the study.

Exclusion Criteria:

  1. History of MS relapses in the previous 3 months.
  2. Neurodegenerative progressive neurological disorders other than progressive MS.
  3. Breastfeeding
  4. History of bleeding disorders
  5. Abnormal results of liver function test at screening (AST or ALT more than twice the upper limit of normal).
  6. Receiving or about to start interferon beta or immunosuppressive medications (e.g. cyclophosphamide, mitoxantrone, methotrexate, mycophenolate mofetil) as these medication can be associated with fatigue.
  7. Starting or changing the dose of other MS disease-modifying medications (including monoclonal antibodies such as rituximab, ocrelizumab, alemtuzumab, daclizumab) within 3 months of baseline visit.
  8. No ongoing steroid treatment and no steroid treatment in the prior month.
  9. Inability to undergo MRI scans (e.g. weight>350 pounds, severe claustrophobia, metal in the body).
  10. Medical terminal conditions.
  11. Currently treated for active malignancy or metastatic malignancy that has been treated in the past 1 year or undergoing extra screening for recurrence
  12. Planned surgery within the following 12 weeks
  13. Planning to move with the following next 12 weeks
  14. Participating in another clinical trial with an experimental medication.
  15. Alcohol or substance abuse, or any other condition that in the investigator's opinion would make the patient unsuitable for this study.
  16. A history of allergic or anaphylactic reaction to NAC, or any component of the preparation.
  17. Clinically unstable medical or psychiatric disorders that require acute treatment.
  18. Active gastrointestinal ulcers.
  19. Subjects taking concomitant medications or supplements known for their glutamatergic effects (e.g., dextromethorphan, D-cycloserine, memantine, lamotrigine, riluzole), antioxidant properties (DMG, TMG, other alternative treatments), or medications with an effect on sleepiness and possibly fatigue such as Provigil, Nuvigil and amantadine within 2 weeks of the baseline visit with the exception of short-term use of dextromethorphan as needed as a cough suppressant. Regular multivitamins will be allowed.
  20. Patients taking anticoagulants
  21. Patients with history of obvious secondary causes of fatigue, such as chronic insomnia, sleep apnea, narcolepsy, restless leg syndrome and significant bladder dysfunction disrupting sleep.
  22. Screening Epworth Sleepiness Scale score greater than 15.
  23. Starting or changing the dose of benzodiazepine, antidepressant, antipsychotics, anti-histamines, or stimulants within a month from the screening visit.
  24. A score of 15 or greater on the Hospital Anxiety and Depression Scale (HADS) depression subscale.
  25. Patients currently treated for asthma.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02804594


Locations
Layout table for location information
United States, California
University of California San Francisco
San Francisco, California, United States, 94158
Sponsors and Collaborators
University of California, San Francisco
Investigators
Layout table for investigator information
Principal Investigator: Emmanuelle Waubant, MD, PhD University of California, San Francisco
  Study Documents (Full-Text)

Documents provided by University of California, San Francisco:
Layout table for additonal information
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02804594    
Other Study ID Numbers: NAC Pilot
First Posted: June 17, 2016    Key Record Dates
Results First Posted: February 18, 2020
Last Update Posted: October 1, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Fatigue
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes