Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, MS, Melatonin, Supplement
Brief summary
To date, there are no published data on the role of melatonin supplementation or the appropriate dose for patients with multiple sclerosis. Because of the potential benefits of melatonin, this pilot study will be an exploratory investigation to evaluate the effect of supplementing melatonin in subjects with multiple sclerosis who are taking an oral disease modifying therapy (DMT) for 6 months or longer. It is our intent that the results of this study will support the rationale and be a prelude to a larger trial which can focus on clinical efficacy of melatonin therapy outcomes.
Detailed description
The primary objective of this study is to evaluate the change in 24 hour urinary 6-sulfatoxymelatonin (6SMT) collected for 24 hours in two twelve hour sessions. The secondary objectives are to evaluate the change in serum morning melatonin level. In addition, quality of life (QOL) measures will be assessed including the Modified Fatigue Impact Scale (MFIS), Multiple Sclerosis Impact Scale (MSIS-29), and the Pittsburgh Sleep Quality Index (PSQI). Clinical objectives include the number of relapses during the trial and a change in the Patient Determined Disease Steps (PDDS) & Performance Scales (PS). The pilot study is a one-year randomized, rater- and dose-blinded trial evaluating the potential role of melatonin in subjects with relapsing multiple sclerosis who have been taking a stable dose of an oral disease modifying therapy (DMT) for at least 6 months. The oral DMTs include dimethyl fumarate, fingolimod, teriflunomide, diroximel fumarate, siponimod, and ozanimod. Thirty subjects with relapsing forms of multiple sclerosis who meet all of the eligibility criteria will be enrolled at Providence Neurological Specialties in Portland, Oregon.
Interventions
DRUG3 mg Melatonin
3 mg melatonin once each day
DRUG5 mg Melatonin
5 mg Melatonin once each day
Sponsors
Providence Health & Services
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study is blinded to patients and providers.
Intervention model description
Subjects will be randomly assigned to receive melatonin at 3 milligrams (mg) once a day or 5mg once a day. The study drug will be taken at 21:00 each day ± 2 hours.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female subjects with relapsing forms of MS who have been on a stable dose of dimethyl fumarate, fingolimod, teriflunomide, diroximel fumarate, siponimod, or ozanimod for 6 months or longer * Confirmed diagnosis of Relapsing MS * Women of childbearing potential must employ proven methods to prevent pregnancy during the course of the trial; the acceptable method will be left to the judgment of the investigator * Not pregnant or lactating * No evidence of significant cognitive or psychiatric disorder * Able to understand the purpose and risks of the study * Must be willing to sign an informed consent and follow the protocol requirements
Exclusion criteria
* Use of melatonin within 30 days of enrollment * The addition of any sleep aide or change in dose within 30 days of enrollment or during the trial * The addition or change in dose of Vitamin D within 30 days of enrollment or during the trial * Change in DMT during the trial * Steroid therapy within 30 days of enrollment * Use of anticoagulation at the time of enrollment and during the trial * The addition of an antidepressant is not allowed during the study period; if on an antidepressant at screening, the dose must be stable 30 days prior to enrollment and dose changes are prohibited during the study * The addition or change in dose of any stimulants, including but not limited to, amantadine, armodafinil, methylphenidate, or modafinil within 30 days of enrollment or during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urine Melatonin Levels | Baseline (month 0), Month 3, Month 6, and Month 12 | Changes in urinary 6-SMT in 24 hours, urine measured in nanograms per gram of creatinine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Melatonin Level | Baseline (month 0), Month 3, Month 6, and Month 12 | Changes in morning blood levels of melatonin |
| Multiple Sclerosis Impact Scale-29 (MSIS-29) | Baseline (month 0), Month 3, Month 6, and Month 12 | Multiple Sclerosis Impact Scale (MSIS) is a patient reported outcome (PRO) measure, consisting of two subscales- physical impact of MS (20 items) and psychological impact (9 items). It asks subject to rate the impact MS has their daily life in the past 2 weeks (1=low impact to 4=large impact). Individual item scores are summed to create a raw score, which is then transformed on a scale from 0 to 100 for each subscale. Higher scores indicate greater impact of MS on QoL. |
| Modified Fatigue Impact Scale (MFIS) | Baseline (month 0), Month 3, Month 6, and Month 12 | Changes in the MFIS: Modified Fatigue Impact Scale (MFIS) is a PRO, consisting of 21 statements that describe the effect of fatigue. Subject will choose an answer (0= never to 4=always) that best describes how fatigue has affected them in the past 4 weeks. Item scores are summed to a total score. The total MFIS score ranges from 0 to 84, with three subscales: Physical range 0-36, Cognitive range 0-40, and Psychosocial range 0-8. Higher scores indicate higher level of fatigue. |
| Relapse Rate | 12 months | Number of MS relapses during study |
| Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Baseline (month 0), Month 3, Month 6, and Month 12 | Changes in PDDS-PS: Patient Determined Disease Steps and Performance Scales (PDDS-PS) is a PRO for MS disease status. Performance Scales (PS) has 8 subscales: mobility range, hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range. Subject self-classify their level of disability on a 0 to 8 scale (0=Normal to 8=Bedridden) with 8 being the most disabled for PDDS. For Performance Scales (PS) subject self-classify their level of disability on a 0 to 6 scale (0=Normal to 6=Bedridden) with 6 being the most disabled for PS - Mobility. Subject self-classify their level of disability on 0 to 5 scale (0=Normal to 5=Total Disability) with 5 being the most disabled for PS - hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range. |
| Pittsburgh Sleep Quality Index (PSQI) | Baseline (month 0), Month 3, Month 6, and Month 12 | Changes in PSQI: Pittsburgh Sleep Quality Index (PSQI) asks 10 sets of questions about sleep quality and pattern in the past month. The scale derive 7 component scores based on a 0 to 3 scale (0= no difficulty, 3=severe difficulty) which are summed to a global score (range 0 to 21). Higher scores indicates worse sleep quality. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 mg Melatonin Subjects will receive 3 mg melatonin once a day.
3 mg Melatonin: 3 mg melatonin once each day | 15 |
| 5 mg Melatonin Subjects will receive 5 mg melatonin once a day.
5 mg Melatonin: 5 mg Melatonin once each day | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | 3 mg Melatonin | 5 mg Melatonin | Total |
|---|---|---|---|
| Age, Continuous | 57 Years | 53 Years | 54 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Prior MS treatment Received | 15 Participants | 15 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 14 Participants | 29 Participants |
| Region of Enrollment United States | 15 Participants | 15 Participants | 30 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 14 / 15 | 15 / 15 |
| serious Total, serious adverse events | 1 / 15 | 0 / 15 |
Outcome results
Primary
Urine Melatonin Levels
Changes in urinary 6-SMT in 24 hours, urine measured in nanograms per gram of creatinine
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study. Numbers analyzed in serum and urine outcomes may differ in the numbers analyzed in the questionnaire outcomes (PSQI,MFIS,MSIS-29, PDDS-PS) due to patients completing questionnaires but samples not being collected or analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 3 mg Melatonin | Urine Melatonin Levels | Month 12 | 1,020 nanograms per gram of creatinine |
| 3 mg Melatonin | Urine Melatonin Levels | Baseline (month 0) | 19 nanograms per gram of creatinine |
| 3 mg Melatonin | Urine Melatonin Levels | Month 3 | 925 nanograms per gram of creatinine |
| 3 mg Melatonin | Urine Melatonin Levels | Month 6 | 1,030 nanograms per gram of creatinine |
| 5 mg Melatonin | Urine Melatonin Levels | Month 6 | 2,509 nanograms per gram of creatinine |
| 5 mg Melatonin | Urine Melatonin Levels | Month 12 | 4,339 nanograms per gram of creatinine |
| 5 mg Melatonin | Urine Melatonin Levels | Month 3 | 1,687 nanograms per gram of creatinine |
| 5 mg Melatonin | Urine Melatonin Levels | Baseline (month 0) | 22 nanograms per gram of creatinine |
Secondary
Modified Fatigue Impact Scale (MFIS)
Changes in the MFIS: Modified Fatigue Impact Scale (MFIS) is a PRO, consisting of 21 statements that describe the effect of fatigue. Subject will choose an answer (0= never to 4=always) that best describes how fatigue has affected them in the past 4 weeks. Item scores are summed to a total score. The total MFIS score ranges from 0 to 84, with three subscales: Physical range 0-36, Cognitive range 0-40, and Psychosocial range 0-8. Higher scores indicate higher level of fatigue.
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 3 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 3 months visit | 16.5 scores on a MFIS scale |
| 3 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 6 months visit | 22 scores on a MFIS scale |
| 3 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 12 months visit | 20.5 scores on a MFIS scale |
| 3 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - Baseline | 25 scores on a MFIS scale |
| 5 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 12 months visit | 19.0 scores on a MFIS scale |
| 5 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 6 months visit | 21.5 scores on a MFIS scale |
| 5 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - Baseline | 24 scores on a MFIS scale |
| 5 mg Melatonin | Modified Fatigue Impact Scale (MFIS) | MFIS Score [0-84] - 3 months visit | 22.0 scores on a MFIS scale |
Secondary
Multiple Sclerosis Impact Scale-29 (MSIS-29)
Multiple Sclerosis Impact Scale (MSIS) is a patient reported outcome (PRO) measure, consisting of two subscales- physical impact of MS (20 items) and psychological impact (9 items). It asks subject to rate the impact MS has their daily life in the past 2 weeks (1=low impact to 4=large impact). Individual item scores are summed to create a raw score, which is then transformed on a scale from 0 to 100 for each subscale. Higher scores indicate greater impact of MS on QoL.
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - Baseline | 8.0 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - Baseline | 10 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 3 Months Visit | 4.5 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 6 months visit | 7.0 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 12 months visit | 9.00 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 3 months visit | 12.5 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 6 months visit | 3.0 MSIS-29 Score |
| 3 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 12 months visit | 8.0 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 6 months visit | 5.00 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - Baseline | 14.0 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 12 months visit | 11.0 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 3 months visit | 8.0 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - Baseline | 9.00 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 12 months visit | 8.00 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Physical - 3 Months Visit | 8.00 MSIS-29 Score |
| 5 mg Melatonin | Multiple Sclerosis Impact Scale-29 (MSIS-29) | Psychological - 6 months visit | 9.50 MSIS-29 Score |
Secondary
Patient Determined Disease Steps - Performance Scale (PDDS-PS)
Changes in PDDS-PS: Patient Determined Disease Steps and Performance Scales (PDDS-PS) is a PRO for MS disease status. Performance Scales (PS) has 8 subscales: mobility range, hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range. Subject self-classify their level of disability on a 0 to 8 scale (0=Normal to 8=Bedridden) with 8 being the most disabled for PDDS. For Performance Scales (PS) subject self-classify their level of disability on a 0 to 6 scale (0=Normal to 6=Bedridden) with 6 being the most disabled for PS - Mobility. Subject self-classify their level of disability on 0 to 5 scale (0=Normal to 5=Total Disability) with 5 being the most disabled for PS - hand function range, vision range, fatigue range, cognition range, bowel/bladder range, sensory range, and spasticity range.
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 3 Month Visit | 1.0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 6 Month Visit | 0.50 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - Baseline | 0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 6 Month | 0.500 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - Baseline | 2.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 6 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 6 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - Baseline | 1.0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 12 Month Visit | 0.50 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 3 Month | 0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 12 Month | 0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 3 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 6 Month | 0.500 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 12 Month | 0.500 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 3 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 6 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 3 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 6 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 12 Month | 1.50 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 3 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 6 Month | 0.500 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 3 Month | 0.500 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 6 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 3 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 3 Month | 0 scores on a PDDS-PS scale |
| 3 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 12 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 6 Month | 0.500 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - Baseline | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 3 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 6 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 12 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - Baseline | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 6 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - 12 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - Baseline | 2.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 6 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 3 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 3 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 6 Month | 0.500 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 12 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 3 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - 12 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 6 Month | 2.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 3 Month Visit | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 6 Month Visit | 0.50 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - Baseline | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Patient Determined Disease Steps - 12 Month Visit | 1.0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - Baseline | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Fatigue - 12 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 3 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 6 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Spasticity - Baseline | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Mobility - 12 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - Baseline | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 3 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Bowel/Bladder Range - 6 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Cognition Range - 3 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Hand Function - 12 Month | 0 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Sensory Range - 3 Month | 1.00 scores on a PDDS-PS scale |
| 5 mg Melatonin | Patient Determined Disease Steps - Performance Scale (PDDS-PS) | Performance Scale - Vision Range - Baseline | 0 scores on a PDDS-PS scale |
Secondary
Pittsburgh Sleep Quality Index (PSQI)
Changes in PSQI: Pittsburgh Sleep Quality Index (PSQI) asks 10 sets of questions about sleep quality and pattern in the past month. The scale derive 7 component scores based on a 0 to 3 scale (0= no difficulty, 3=severe difficulty) which are summed to a global score (range 0 to 21). Higher scores indicates worse sleep quality.
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 3 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - Base Line | 7.0 PSQI Score |
| 3 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 3 month Visit | 5.5 PSQI Score |
| 3 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 6 months visit | 6.0 PSQI Score |
| 3 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 12 month Visit | 5.0 PSQI Score |
| 5 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 12 month Visit | 7.0 PSQI Score |
| 5 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - Base Line | 6.0 PSQI Score |
| 5 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 6 months visit | 8.0 PSQI Score |
| 5 mg Melatonin | Pittsburgh Sleep Quality Index (PSQI) | PSQI Global - 3 month Visit | 9.0 PSQI Score |
Secondary
Relapse Rate
Number of MS relapses during study
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 3 mg Melatonin | Relapse Rate | o Relapse | 13 Participants |
| 3 mg Melatonin | Relapse Rate | 1 Relapse | 2 Participants |
| 5 mg Melatonin | Relapse Rate | o Relapse | 15 Participants |
| 5 mg Melatonin | Relapse Rate | 1 Relapse | 0 Participants |
Secondary
Serum Melatonin Level
Changes in morning blood levels of melatonin
Time frame: Baseline (month 0), Month 3, Month 6, and Month 12
Population: Number analyzed in one or more rows differs from overall number analyzed due to patients withdrawing or being withdrawn throughout the course of the study. Numbers analyzed in serum and urine outcomes may differ in the numbers analyzed in the questionnaire outcomes (PSQI,MFIS,MSIS-29, PDDS-PS) due to patients completing questionnaires but samples not being collected or analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 3 mg Melatonin | Serum Melatonin Level | Baseline (Month 0) | 5 pg/ml |
| 3 mg Melatonin | Serum Melatonin Level | Month 3 | 14 pg/ml |
| 3 mg Melatonin | Serum Melatonin Level | Month 6 | 35 pg/ml |
| 3 mg Melatonin | Serum Melatonin Level | Month 12 | 29 pg/ml |
| 5 mg Melatonin | Serum Melatonin Level | Month 12 | 97 pg/ml |
| 5 mg Melatonin | Serum Melatonin Level | Baseline (Month 0) | 5 pg/ml |
| 5 mg Melatonin | Serum Melatonin Level | Month 6 | 72 pg/ml |
| 5 mg Melatonin | Serum Melatonin Level | Month 3 | 69 pg/ml |