Multiple Sclerosis (MS) - Relapsing-remitting
Conditions
Keywords
ublituximab, gait function, disease progression, perturbed walking, Cognition
Brief summary
The purpose of this study is to test if ublituximab changes walking functions and fall risk in people with relapsing multiple sclerosis (RMS). Twenty-five qualified people with RMS will undergo a 48-week ublituximab treatment. Before, 24 weeks into, and after the treatment, their ambulatory function, disability status, and cognition will be assessed. Additionally, they will experience large-scale slip perturbations on a treadmill under the protection of a safety harness at the last assessment. The outcome measures will be compared across the assessments to examine the effects of ublituximab on improving their walking function, disability status, cognition, and the responses to the unexpected slip perturbation.
Detailed description
The primary objective of this single-arm and pretest-posttest study will be to examine the effects of treatment with ublituximab on ambulatory functions during unperturbed walking and large-scale gait slips (dynamic gait stability and slip-fall) among people with relapsing MS over a 12-month treatment period. Additionally, the effects of ublituximab on disease progression and cognitive functions will be evaluated. Twenty-five qualified people with relapsing multiple sclerosis (RMS) will be enrolled to this study. Before the treatment, their ambulatory functions during regular walking will be assessed in terms of their spatiotemporal gait parameters. This assessment is considered the baseline test. Their disease progression will be evaluated by the neurological exam and serum neurofilament light chain. Their cognitive function will be tested by the Montreal Cognitive Assessment. Then, they will undergo the 48-week ublituximab treatment. At the mid-point of the treatment period, they will attend another assessment session, which is identical to the baseline session. Immediately after the 48-week treatment, the same assessments will be executed again as the baseline test. In addition, all participants will experience repeated unexpected slip perturbations while walking on a treadmill under the protection of a full-body safety harness. Their response to the the slips will be quantified by their dynamic balance, reaction times of the lower leg muscles, and adaptation rate to the repeated slips. All the measurements will be analyzed to identify the effects of ublituximab on ambulatory functions, disease progression, and cognitive status of people with relapsing multiple sclerosis. Our findings will potentially lead to earlier adoption of this highly efficacious disease-modifying treatment and thus likely improve long-term patient care outcomes. This study will uncover how ublituximab impacts ambulatory function and mobility among people with relapsing MS. This will augment our current understanding of ublituximab which focuses on the aspect of the disease progression. Given mobility is critical for people with MS to maintain their employment, independence, participation in social events, and thus the quality of life, this study will have great potential to scientifically enhance our scientific understanding of effects of ublituximab and to clinically improve patient care.
Interventions
DRUGUblituximab
The participants will receive 48 weeks of treatment with ublituximab.
Sponsors
Georgia State University
Atlanta Neuroscience Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Ability to provide written, informed consent and to be compliant with the schedule of protocol assessments. 2. Ages between 18 and 55 years old at screening. 3. Clinically confirmed active, relapsing forms of MS based on the revised McDonald criteria. 4. Can walk at least 25 feet independently with or without assistive devices at screening. 5. Can stand independently for at least 30 seconds. 6. Not pregnant at screening and throughout the study. * A negative urine or serum pregnancy test must be available for premenopausal women and for women \< 12 months after the onset of menopause at screening, unless they have undergone surgical sterilization. * Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of \< 1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. * A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of the ovaries and/or uterus). * Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tube ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception. * Examples of barrier methods supplemented with the use of spermicide include male or female condom, vaginal ring, cap, diaphragm, or sponge. 7. No other neurological conditions and recent musculoskeletal injuries. 8. Can read and understand English. 9. No significant cognitive impairment.
Exclusion criteria
Basic
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| slip-fall | 48 weeks | The outcome of a slip trial will be deemed a fall if the peak load cell force exceeds 30% of the body weight. |
| Dynamic gait stability during slip | 48 weeks | For a slip, dynamic gait stability will be calculated at two events: the slipping foot touchdown and the recovery foot liftoff. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dynamic gait stability during walking | weeks 0, 24, and 48 | Dynamic gait stability during walking will be calculated based on the theoretical framework of Feasible Stability Region. |
| Spatiotemporal gait parameters during walking | Weeks 0, 24, and 48 | The following parameters will be determined: gait speed, step length, step width, step time, and cadence. These measurements will be used to quantify our participants' ambulatory functions. |
| Leg muscle strength | Weeks 0, 24, and 48 | The maximum voluntary muscle strength will be assessed during maximum voluntary contractions at bilateral knee and ankle joints on an isokinetic dynamometer. |
| Leg Muscle Activities | Weeks 0, 24, and 48 | The surface electromyography activity from four muscles on each leg: the tibialis anterior (TA), medial gastrocnemius (MGAS), vastus lateralis (VLAT), and biceps femoris long head (BFLH), will be recorded. |
| Sway index | Weeks 0, 24, and 48 | It is measured when a patient is standing still for 30 seconds under four conditions: eyes open on a firm surface, eyes closed on a firm surface, eyes open on a foam pad, and eyes closed on a foam pad. |
| Stability index | Weeks 0, 24, and 48 | The overall stability index during stance will be determined based on the center of pressure trace calculated from the ground reaction forces. |
| Expanded Disability Status Scale | Weeks 0, 24, and 48 | The Expanded Disability Status Scale (EDSS) is a method of quantifying disability in multiple sclerosis and monitoring changes in the level of disability. |
| Multiple Sclerosis Functional Composite | Weeks 0, 24, and 48 | The three dimensions of the multiple sclerosis functional composite (MSFC) score: lower extremity motor function, upper extremity motor function, and cognitive function, will be collected based on the guidelines and forms provided by the National MS Society. |
| Prospective falls | Through study completion, an average of 1 year | Participants in both groups will keep track of any falls they experience in the 12 months after the baseline evaluation using the falls questionnaire. |
| Serum neurofilament light chain | Weeks 0, 24, and 48 | The serum neurofilament light chain level serves as a biological marker of neuronal damage and disease progression. It will be collected for all participants in this project. |
Countries
United States
Contacts
CONTACTMittie Mitchell, RN, CRC
Outcome results
None listed