Fatigue, Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Fatigue, Mitochondrial
Brief summary
The purpose of this study is to determine whether MS patients who receive Oral mitoquinone (MitoQ) have less fatigue than those receiving a placebo. A comparison between patient's fatigue scored at baseline and fatigue scored 12 weeks after drug initiation will assess if MitoQ has a significant change in fatigue.
Detailed description
Recruitment of subjects on hold due to COVID-19 pandemic MitoQ is a potent antioxidant dietary supplement with potentially significant immunomodulatory and anti-inflammatory properties. While the cause of MS related fatigue is uncertain, the investigators believe that mitochondria dysfunction and resultant neuronal energy depletion may be an important contributor to fatigue in MS. This clinical trial will evaluate the potential beneficial effects of MitoQ on MS fatigue. It will also explore the effects of MitoQ on cognitive function, quality of life and mood. If enrolled in the study, patients will take two capsules of the study drug or placebo at the same time every day for twelve weeks. There will be 4 study visits where the participant will undergo medical and nervous system examinations, questionnaires, and blood draws. Because it is a placebo-controlled trial, participants will have a 33% chance of receiving either placebo (inactive), 20mg of MitoQ, or 40mg of MitoQ. This will be a blinded randomized study, meaning neither the participant nor the investigator will know who received the placebo or study drug.
Interventions
DRUG20 mg MitoQ
a third of subject will receive 20mg of oral MitoQ
DRUGPlacebo
Subject will receive Placebo
DRUG40mg of MitoQ
a third of subjects will receive 40mg of MitoQ
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The subject and investigator will be blinded.
Intervention model description
Double-blind, randomized trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* MS (any clinical subtype) as diagnosed by the 2017 McDonald criteria * EDSS score of 2 to 8 * complaint of fatigue that has been persistent for at least two months * Modified Fatigue Impact Scale (MFIS) score of 38 or greater
Exclusion criteria
* treatment with systemic glucocorticoids in the prior six weeks * Beck Depression Inventory (BDI) \>31 or BDI-FS\>10 (severe depression) * significant MS exacerbation in prior 30 days * previous use of MitoQ or Coenzyme Q10 (CoQ10) within thirty days of screening appointment * other significant health problem that might increase risk of patient experiencing Adverse Events (AEs), e.g.: * active coronary heart disease * liver disease * pulmonary disease * diabetes mellitus * pregnancy or intending to become pregnant or breastfeeding * unable to complete the self-report forms * unable to give informed consent * prisoners * any condition which would make the patient in the opinion of the investigator unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Fatigue Inventory Scale (MFIS) | Week 1, Week 7, Week 13 | MFIS is a self - reported fatigue survey. Scale 0 - 84. Higher scores indicate a greater impact of fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symbol Digit Modalities Test (SDMT) | Week 1, Week 7, Week 13 | SDMT measures cognitive function. Scale 0-110. Higher scores reflect a better outcome. |
| Expanded Disability Status Scale (EDSS) | 12 weeks | EDSS measures neurological function. Scale 0-10 |
| Beck's Depression Inventory (BDI) | 12 weeks | BDI is a self-reported questionnaire measuring depression. Scale 0-21 |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVijayshree Yadav, MBBS
VA Portland Health Care System, Portland, OR
Participant flow
Recruitment details
Patients seen at the Multiple Sclerosis at Portland VA Medical Center (PORVAMC)and Oregon Health & Science University (OHSU) were main sources of recruitment. PORVAMC and OHSU MS clinics neurologists' referrals, chart reviews of MS patients at PORVAMC and OHSU Electronic medical records using the Mychart tool were used for help with recruitment. We additionally reached to a wide network of interested referring physicians from Portland and its surrounding areas.
Pre-assignment details
Out of 46 screened subjects, 45 were randomized. One subject was NOT randomized due to abnormal screening labs. Two subjects were excluded after randomization (one subject had abnormal screening labs, second subject received IV Iron infusion for anemia). Thus, data from 43 subjects is available for the statistical analysis.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 16 |
| 20mg of MitoQ 20mg of oral mitoquinol | 15 |
| 40mg of MitoQ 40mg of Oral Mitoquinol | 14 |
| Total | 45 |
Baseline characteristics
| Characteristic | Placebo | 20mg of MitoQ | 40mg of MitoQ | Total |
|---|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 8.46 | 55.7 Years STANDARD_DEVIATION 9.32 | 52.6 Years STANDARD_DEVIATION 12.06 | 54.42 Years STANDARD_DEVIATION 9.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 15 Participants | 13 Participants | 44 Participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 10 Participants | 34 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 | 0 / 14 |
| other Total, other adverse events | 2 / 16 | 1 / 15 | 1 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 | 0 / 14 |
Outcome results
Primary
Modified Fatigue Inventory Scale (MFIS)
MFIS is a self - reported fatigue survey. Scale 0 - 84. Higher scores indicate a greater impact of fatigue.
Time frame: Week 1, Week 7, Week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Modified Fatigue Inventory Scale (MFIS) | Week 13 | 39.7 units on a scale | Standard Error 2.8 |
| Placebo | Modified Fatigue Inventory Scale (MFIS) | Week 1 | 46.5 units on a scale | Standard Error 2.8 |
| Placebo | Modified Fatigue Inventory Scale (MFIS) | Week 7 | 45.1 units on a scale | Standard Error 3.1 |
| 20mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 13 | 48.7 units on a scale | Standard Error 2.8 |
| 20mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 1 | 55.2 units on a scale | Standard Error 2.8 |
| 20mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 7 | 50.5 units on a scale | Standard Error 2.9 |
| 40mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 13 | 47.8 units on a scale | Standard Error 3 |
| 40mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 7 | 49 units on a scale | Standard Error 3.1 |
| 40mg of MitoQ | Modified Fatigue Inventory Scale (MFIS) | Week 1 | 54.3 units on a scale | Standard Error 2.9 |
p-value: 0.9489Mixed Models Analysis
Secondary
Beck's Depression Inventory (BDI)
BDI is a self-reported questionnaire measuring depression. Scale 0-21
Time frame: 12 weeks
Secondary
Expanded Disability Status Scale (EDSS)
EDSS measures neurological function. Scale 0-10
Time frame: 12 weeks
Secondary
Symbol Digit Modalities Test (SDMT)
SDMT measures cognitive function. Scale 0-110. Higher scores reflect a better outcome.
Time frame: Week 1, Week 7, Week 13
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Symbol Digit Modalities Test (SDMT) | Week 7 | 33.2 units on a scale | Standard Error 8 |
| Placebo | Symbol Digit Modalities Test (SDMT) | Week 1 | 31.3 units on a scale | Standard Error 8.4 |
| Placebo | Symbol Digit Modalities Test (SDMT) | Week 13 | 32.6 units on a scale | Standard Error 8.4 |
| 20mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 7 | 28.8 units on a scale | Standard Error 8 |
| 20mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 1 | 25.9 units on a scale | Standard Error 8.1 |
| 20mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 13 | 30.4 units on a scale | Standard Error 8.1 |
| 40mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 1 | 33.3 units on a scale | Standard Error 8.4 |
| 40mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 13 | 35.6 units on a scale | Standard Error 8.2 |
| 40mg of MitoQ | Symbol Digit Modalities Test (SDMT) | Week 7 | 36.1 units on a scale | Standard Error 8.2 |