SNPMiner Trials (Home Page)
Report for Mutation T25W
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 9 clinical trials
Clinical Trials
1 Project FARMS: Fall Risk Reduction in Multiple Sclerosis
Over half of persons with multiple sclerosis (MS) report falling over a 6-month period and a majority of those who fall require medical attention for injuries. Importantly, balance dysfunction, muscle weakness, and spasticity are modifiable risk factors for falls among community-dwelling older adults and likely persons with MS. Indeed, there is evidence that these physiological risk factors can be minimized with exercise training in persons with MS and this might translate into a decrease in fall risk as documented in community-dwelling older adults. The investigation will examine the effectiveness of a home-based exercise program that is designed to reduce fall risk by targeting specific fall risk factors including balance dysfunction and two of its latent causes, muscle weakness and spasticity in persons with multiple sclerosis. It is predicted that persons who receive home-based exercise program will have a reduction in fall risk.
NCT01837017 Multiple S Multiple Sclerosis Behavioral: Home-based Exercise MeSH:Multiple Sclerosis Sclerosis
Mobility will be quantified with performance on timed 25 foot walk (T25W), timed up and go (TUG), Six spot step test, 6 minute walk and the MS walking scale-12.. Balance. --- T25W ---
Primary Outcomes
Description: Physiological fall risk will be determined by the physiological profile assessment which assesses physiological function related to fall risk by combining measures of vision, proprioception, lower-limb strength, postural sway, and cognitive function.
Measure: Physiological Fall risk Time: 3 monthsSecondary Outcomes
Description: Mobility will be quantified with performance on timed 25 foot walk (T25W), timed up and go (TUG), Six spot step test, 6 minute walk and the MS walking scale-12.
Measure: Mobility Time: 3 monthsDescription: Balance will be quantified with the Berg Balance scale; self-report of balance impairment (ABC); and force platform metrics (sway range and velocity).
Measure: Balance Time: 3 MonthsDescription: Spasticity will be assessed with the modified ashworth scale.
Measure: Spasticity Time: 3 Months2 Fall Risk Reduction in Multiple Sclerosis: Exercise Versus Behavior
Falls are a serious health concern for persons with multiple sclerosis (MS). Over 50% of persons with MS suffer a fall over a 6-month periodwith the majority of falls resulting in medical attention for injuries (i.e., lacerations, bone fractures, & head injuries). The effects of a fall are often compounded as it can lead to activity curtailment, physiological deconditioning, and institutionalization. Despite the importance of falls in persons with MS, the appropriate prevention strategies (i.e. rehabilitation approaches) are not clear. The purpose of this investigation is to determine whether exercise based or educational based interventions are more suited for fall prevention in older adults with MS.
NCT01956227 Multiple Sclerosis Adult Disease Behavioral: Home-based exercise Behavioral: Education Behavioral: Exercise plus Education MeSH:Multiple Sclerosis Sclerosis
Walking speed was quantified with the Timed 25-Foot Walk (T25W), walking endurance was assessed with the 6-Minute Walk (6MW), and functional mobility was quantified with the Timed Up and Go (TUG) . --- T25W ---
Primary Outcomes
Measure: Fall incidence Time: 3 monthsSecondary Outcomes
Description: Physiological fall risk will be determined by the short form of the Physiological Profile Assessment (PPA)(Lord, 2003). The PPA is a standardized test battery which assesses vision (edge contrast sensitivity), lower limb proprioception, strength (knee extension), postural sway, and cognitive function (simple hand reaction time). The outcome of each test will be combined to generate an overall fall risk score
Measure: Physiological Fall Risk Time: 3 MonthsDescription: Specific measures of walking speed, endurance, coordination and self-reported walking function scale will be employed to assess overall mobility of each person. Walking speed was quantified with the Timed 25-Foot Walk (T25W), walking endurance was assessed with the 6-Minute Walk (6MW), and functional mobility was quantified with the Timed Up and Go (TUG) . The Multiple Sclerosis Walking Scale-12 (MSWS-12) will be used as a self-reported measure of walking impairment.
Measure: Mobility Time: 3 monthsDescription: To assess balance (e.g. postural control), we conducted a clinical assessment To measure balance the Berg Balance Scale (BBS) and self-reports of balance confidence will be used. The BBS is a clinical assessment of balance. Scores on the BBS range from 0-56 with higher scores indicating greater balance. The Activities-Specific Balance Confidence (ABC) scale was used as a measure of balance confidence.
Measure: Balance Time: 3 Months3 A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Satralizumab (SA237) as Monotherapy in Patients With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD)
The objectives of this study are to evaluate the efficacy, safety, pharmacodynamic, pharmacokinetic and immunogenic profiles of satralizumab in participants with NMO and NMOSD.
NCT02073279 Neuromyelitis Optica (NMO) NMO Spectrum Disorder (NMOSD) Drug: Satralizumab Drug: Placebo MeSH:Neuromyelitis Optica
A higher score reflects a better health state.. Change from Baseline Over Time in the Timed 25-Foot Walk (T25W). --- T25W ---
The T25W is the measurement to assess walking ability. --- T25W ---
Primary Outcomes
Measure: Time to First Protocol-Defined Relapse in the Double-Blind Period Time: From the date of randomization until the first occurrence of a protocol-defined relapse throughout the double-blind period (up to approximately 50 months)Secondary Outcomes
Description: The VAS for pain is a subjective measure and it consists of a 100 millimeter (mm) line with two end points representing 'no pain' to 'pain as bad as it could be'. Participants are asked to rate their pain by placing a mark on the line corresponding to their current level of pain. The distance along the line from the 'no pain' marker is then measured with a ruler giving a pain score out of 10.
Measure: Change from Baseline to Week 24 in the Visual Analogue Scale (VAS) Score for Pain Time: Baseline, Week 24Description: FACIT fatigue scale includes 13 statements, which measures fatigue/asthenia for participants with chronic, life-threatening illnesses. For each question, a participant rates his/her condition for the past week on a 5-point Likert scale ranging from 0 (not at all) to 4 (very much). A score is calculated by averaging the individual question scores, with lower scores indicative of less fatigue.
Measure: Change from Baseline to Week 24 in the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score Time: Baseline, Week 24Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the Short Form Generic Health Survey (SF-36) Bodily Pain Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 General Health Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Mental Health Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Physical Functioning Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Role-Emotional Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Role-Physical Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Social Role Functioning Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Vitality Domain Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Mental Component Summary Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The SF-36 domain scores range from 0-100. Higher scores indicate better quality of life.
Measure: Change from Baseline Over Time in the SF-36 Physical Component Summary Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The EQ-5D is a participant-answered questionnaire measuring 5 dimensions of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with 3 possible response categories: 1) no problems; 2) some problems; 3) severe problems. The EQ-5D index score is scored on a scale of -0.2 to 1. A higher score reflects a better health state.
Measure: Change from Baseline Over Time in the EuroQoL-5 Dimensions (EQ-5D) Index Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The T25W is the measurement to assess walking ability. The time (in seconds) that it takes the participant to walk 25 feet is measured.
Measure: Change from Baseline Over Time in the Timed 25-Foot Walk (T25W) Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Measure: Percentage of Participants Who Are Relapse-Free Over Time Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Annualized Relapse Rate Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Description: The mRS is a 7-point disability scale that assesses the degree of disability in patients with neurological impairment. Possible scores range from 0 (no symptoms at all) up to 6 (death). Higher scores reflect increased disability.
Measure: Change from Baseline Over Time in Modified Rankin Scale (mRS) Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The ZBI is the measurement to assess caregiver burden. The 22 items ask for the strain caregivers perceive. Responses range from 0 (never) to 4 (nearly always). The overall ZBI score ranges from 0 to 88. The higher the total score, the heavier the perceived burden.
Measure: Change from Baseline Over Time in Zarit Burden Interview (ZBI) Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Description: The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.
Measure: Change from Baseline Over Time in Expanded Disability Status Scale (EDSS) Score Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)Measure: Change from Baseline Over Time in Visual Acuity (Snellen Chart) Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Change from Baseline Over Time in Low-Contrast Visual Acuity, as Assessed Using the Low-Contrast Sloan Letter Chart (LCSLC) Time: Baseline and every 24 weeks thereafter until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Number of Participants with at Least One Adverse Event by Severity Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Number of Participants with at Least One Serious Adverse Event by Severity Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Number of Participants with Non-Serious Adverse Events of Special Interest by Severity Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Number of Participants with Selected Adverse Events by Severity Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 7.25 years)
Measure: Number of Participants by Columbia-Suicide Severity Rating Scale (C-SSRS) Scores Time: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 12 weeks thereafter of open-label extension period (up to approximately 7.25 years)
Measure: Serum Satralizumab Concentration Over Time Time: Baseline, Weeks 2, 4, 5, 6, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 24 weeks thereafter of open-label extension period (up to approximately 7.25 years)
Measure: Serum Interleukin-6 (IL-6) Concentration Over Time Time: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 7.25 years)
Measure: Serum Soluble IL-6 Receptor (sIL-6R) Concentration Over Time Time: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 7.25 years)
Measure: Serum High Sensitivity C-Reactive Protein (hsCRP) Concentration Over Time Time: Baseline, Weeks 2, 4, 8, and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks of open-label extension period (up to approximately 7.25 years)
Measure: Blood Anti-Aquaporin-4 (AQP4) Antibody Concentration Over Time Time: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period; every 24 weeks for first 48 weeks of open-label extension period (up to approximately 7.25 years)
Measure: Blood Plasmablast Concentration Over Time Time: Baseline, Weeks 2, 4, 8, 12, 24, 48, and every 24 weeks thereafter of double-blind period (up to approximately 50 months)
Measure: Number of Participants with Anti-Drug Antibodies to Satralizumab Time: Baseline and every 4 weeks thereafter of double-blind period; every 4 weeks for first 48 weeks and every 24 weeks thereafter of open-label extension period (up to approximately 7.25 years)
4 Open-label, Single-center, Single-arm Futility Trial Evaluating Oral Domperidone 10mg QID for Reducing Progression of Disability in Patients With Secondary Progressive Multiple Sclerosis (SPMS)
The purpose of this clinical trial is to determine if Domperidone in a dose of 40 mg daily can prevent worsening of walking ability in people secondary progressive MS. The number of participants in this study will be 62. A maximum of 75 people with secondary progressive MS will be included. Each patient will be followed for 12 months from inclusion. Domperidone is a medication which has been shown to increase levels of the hormone prolactin. The best understood function of prolactin is the stimulation of milk production in women after delivery. However, the increase in prolactin levels seen in patients treated with standard doses of Domperidone (in doses of up to 80mg per day) usually does not lead to clinical symptoms. Prolactin has been shown to improve myelin repair in mice. Domperidone therefore may also improve myelin repair in people with MS. Domperidone is currently approved in Canada to treat slow moving bowels and nausea, for instance in patients with Parkinson's Disease or Diabetes Mellitus, where too slowly moving bowels can cause constipation. Domperidone is available as a tablet that is usually taken four times per day. Doses up to 80mg per day may be used but we estimate that a dose of only 40mg daily will be needed to stimulate myelin repair. Domperidone is usually well tolerated.
NCT02308137 Multiple Sclerosis, Secondary Progressive Drug: Domperidone MeSH:Neoplasm Metastasis Multiple Sclerosis Multiple Sclerosis, Chronic Progressive Sclerosis
Timed 25-Foot Walk (T25W). --- T25W ---
Primary Outcomes
Description: quantitative ambulation performance test
Measure: Timed 25-Foot Walk (T25W) Time: up to 12 monthsSecondary Outcomes
Description: brief, standardized, quantitative test of upper extremity
Measure: 9-Hole Peg Test Time: administered at baseline, one month, 6 months, and 12 monthsDescription: measures cognitive processing speed and working memory
Measure: Symbol Digit Modalities Test Time: administered at baseline, one month, 6 months, and 12 monthsDescription: EDSS is the standard measure of neurologic impairment that is used to describe disability in MS. The neurological assessment comprises seven functional systems.
Measure: Functional Systems and Expanded Disability Status Scale (EDSS) Time: administered at baseline, one month, 6 months, and 12 monthsDescription: structured, self-report questionnaire with 21 itmes concerning how fatigue impacts patient's life
Measure: Modified Fatigue Impact Scale (MFIS) Time: administered at baseline, one month, 6 months, and 12 monthsDescription: 54-item multidimensional health-related quality of life measure that combines both generic and MS-specific items
Measure: Multiple Sclerosis Quality of Life Scale 54 item version Time: administered at baseline, one month, 6 months, and 12 months5 A Phase 1, Two-part, Open-label Dose-escalation and Double-blind, Placebo-controlled Dose-expansion Study With an Open-label Extension to Evaluate the Safety and Efficacy of ATA188 in Subjects With Progressive Multiple Sclerosis
The purpose of this study is to evaluate the safety and tolerability of ATA188 as a monotherapy in Parts 1 and 2, to determine the recommended Part 2 dose (RP2D) of ATA188 as monotherapy in Part 1, and to evaluate the effect of ATA188 treatment on biological markers of disease activity in cerebral spinal fluid in Part 2 in participants with progressive forms of multiple sclerosis (MS) (primary progressive multiple sclerosis [PPMS] and secondary progressive multiple sclerosis [SPMS]).
NCT03283826 Primary Progressive Multiple Sclerosis Secondary Progressive Multiple Sclerosis Biological: ATA188 Drug: Placebo MeSH:Multiple Sclerosis Multiple Sclerosis, Chronic Progressive Sclerosis
Part 2: Change from baseline in clinical disability as assessed by the EDSS score and/or Timed 25 foot Walk (T25W) and/or 9-hole Peg Test (9HPT). --- T25W ---
Primary Outcomes
Description: Safety and tolerability
Measure: Part 1 and Part 2: Incidence of adverse events Time: At 12 months after the first dose of study drugMeasure: Part 1: Incidence of clinically significant changes in laboratory tests, electrocardiograms (ECGs), and vital signs Time: At 12 months after the first dose of study drug
Description: Dose assessment
Measure: Part 1: Recommended Part 2 dose of ATA188 monotherapy Time: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation part (approximately 1 year)Description: Antibody assessment and quantification
Measure: Part 2: Change from baseline in immunoglobulin G (IgG) index, including quantification of IgG production Time: At 12 months after the first dose of study drugSecondary Outcomes
Description: Changes in disability score
Measure: Part 1: Change from baseline in expanded disability status scale (EDSS) score Time: At 12 months after the first dose of study drugDescription: Changes in disability score
Measure: Part 2: Change from baseline in clinical disability as assessed by the EDSS score and/or Timed 25 foot Walk (T25W) and/or 9-hole Peg Test (9HPT) Time: At 12 months after the first dose of study drugDescription: Change in MRI activity
Measure: Part 2: Change from baseline in cervical spinal cord volume and whole brain volume on MRI scans Time: At 12 months after the first dose of study drugDescription: Change in MRI activity
Measure: Part 2: Change from baseline in the number of Gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans Time: At 12 months after the first dose of study drug6 Effect of Alemtuzumab on Microglial Activation Assessed Using Novel [F-18]-Based Positron Emission Tomography (PET) Ligand in Multiple Sclerosis
Specific Aims The specific aims of the study are: - Primary Objective: To assess the effect of alemtuzumab on microglial activation in MS patients. The hypothesis is that alemtuzumab reduces microglial activation in MS, which may mediate its effect on reducing conversion of RRMS patients to SPMS, and its effects on cognition, including cognitive fatigue. - Secondary Objective: To determine the time course of effect of alemtuzumab on microglial activation. The hypothesis is that alemtuzumab reduces microglial activation at 6 months after initiation of treatment and this effect persists and is accentuated at 18 years, i.e. after administration of the second course
NCT03983252 Multiple Sclerosis Drug: [F-18]PBR06 MeSH:Multiple Sclerosis Sclerosis
Non Imaging/Clinical Data The following non-imaging/clinical data will be obtained: Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Minimal Assessment of Cognitive Function Scale in MS (MACFIMS) battery Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Modified fatigue Impact Scale (MFIS) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS) --- T25W ---
Primary Outcomes
Description: PET outcome measure change at 18 months from baseline
Measure: PET Uptake/Standardized uptake value ratio (SUVR) change Time: baseline and 18 monthsSecondary Outcomes
Description: PET outcome measure change at 6 months from baseline
Measure: PET Uptake/Standardized uptake value ratio (SUVR) change Time: baseline and 6 monthsDescription: MRI outcome measure change at 18 months from baseline
Measure: T2/FLAIR lesion load change Time: baseline and 18 monthsDescription: MRI outcome measure change at 18 months from baseline
Measure: Whole brain/deep gray matter atrophy change Time: baseline and 18 monthsDescription: Clinical outcome measure change at 18 months from baseline; Scale Range: 0-10; Higher values represent worse outcomes
Measure: Expanded Disability Status Scale (EDSS) change Time: baseline and 18 monthsDescription: Clinical outcome measure change at 18 months from baseline
Measure: Timed 25-foot walk (T25FW) change Time: baseline and 18 monthsDescription: Clinical outcome measure change at 18 months from baseline; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes
Measure: Modified Fatigue Impact Scale (MIFS) change Time: baseline and 18 monthsDescription: Clinical outcome measure change at 18 months from baseline
Measure: Minimal Assessment of Cognitive Function in MS (MACFIMS) change Time: baseline and 18 months7 A Multicenter, Longitudinal, Open-Label, Single-Arm Study Describing Cognitive Processing Speed Changes in Relapsing Multiple Sclerosis Subjects Treated With Ozanimod (RPC-1063)
This is a multicenter, longitudinal, single-arm, open-label study to describe the change from baseline in cognitive processing speed, measured by the SDMT, in subjects with RMS treated with ozanimod HCl 1 mg at 3 years. All subjects will receive orally administered ozanimod HCl 1 mg. The primary efficacy endpoint is the proportion of subjects with a clinically meaningful increase in raw score of ≥ 4 points or 10% from baseline (improved). The treatment period is 36 months. For subjects who discontinue the study, there will be a 30-day (± 15 days) and a 90-day (± 10 days) Safety Follow-up Visit. There is no planned protocol extension following the end of the study. Approximately 250 subjects with RMS will be recruited for this study. Subjects with RMS will be enrolled in this study if they have received ≤1 DMT, have an EDSS ≤ 3.5, and have been diagnosed with RMS within 5 years of study entry. The Investigator will be responsible for the overall conduct of the study at the site, confirmation of subject eligibility, routine study subject clinical management including for MS relapses, and management of AEs.
NCT04140305 Multiple Sclerosis Drug: RPC-1063 MeSH:Multiple Sclerosis Sclerosis
Timed 25-foot Walk (T25W). --- T25W ---
Disability progression assessed by 20% worsening from baseline over 3 years on T25W. --- T25W ---
Primary Outcomes
Description: Symbol Digit Modalities Test
Measure: Proportion of subjects with an increase in raw score of ≥ 4 points or 10% from baseline (improved) Time: Up to approximately 3 yearsSecondary Outcomes
Description: Symbol Digit Modalities Test
Measure: Proportion of subjects with a decrease in raw score of ≥ 4 points or 10% from baseline (worsened) Time: Up to approximately 3 yearsDescription: Symbol Digit Modalities Test
Measure: Proportion of subjects with a raw score change from baseline who do not meet the improved or worsened definition (stable) Time: Up to approximately 3 yearsDescription: Symbol Digit Modalities Test
Measure: Proportion of subjects with an increase in raw score of ≥ 3 points from baseline Time: Up to approximately 3 yearsDescription: Symbol Digit Modalities Test
Measure: Proportion of subjects with a decrease in raw score of ≥ 3 points from baseline Time: Up to approximately 3 yearsDescription: The SDMT is a measure of cognitive processing speed
Measure: Change from baseline in Symbol Digit Modalities Test (SMDT) Time: Up to approximately 3 yearsDescription: Magnetic resonance imaging (MRI) brain volume
Measure: Percent change from baseline in thalamic, cortical grey matter, whole brain, lateral ventricular, and MOV volumes Time: Up to approximately 3 yearsDescription: Magnetic Resonance Imaging
Measure: Proportion of subjects free of gadolinium enhancing (GdE) lesions over 3 years Time: Up to approximately 3 yearsDescription: Magnetic Resonance Imaging
Measure: GdE lesion volume over 3 years Time: Up to approximately 3 yearsDescription: Magnetic Resonance Imaging
Measure: Number of unique new or enlarging hyperintense T2-weighted lesions and their volume from baseline to Year 3 Time: Up to approximately 3 yearsDescription: Magnetic Resonance Imaging
Measure: Number of unique new or enlarging hypointense T1 weighted lesions and their volume from baseline to Year 3 Time: Up to approximately 3 yearsDescription: Change is TSQM score over 3 years
Measure: Treatment Satisfaction Questionnaire for Medication (TSQM v1.4) Time: Up to approximately 3 yearsDescription: Change in WPAI score over 3 years
Measure: Work Productivity and Activity Impairment-Multiple Sclerosis (WPAI-MS) Time: Up to approximately 3 yearsDescription: The Fatigue Severity Scale (FSS) questionnaire contains nine statements that attempt to explore severity of fatigue symptoms.
Measure: Fatigue Severity Scale (FSS) Time: Up to approximately 3 yearsDescription: The MSQOL-54 is a multidimensional health-related QOL measure that combines both generic and MS-specific items into a single instrument
Measure: Multiple Sclerosis Quality of Life-54 (MSQOL-54) Time: Up to approximately 3 yearsDescription: The HADS was developed to identify anxiety disorders and depression among subjects in nonpsychiatric hospital clinics
Measure: Hospital Anxiety and Depression Scale (HADS) Time: Up to approximately 3 yearsDescription: Change in relapse rate over 3 years
Measure: Annualized relapse rate (ARR) Time: Up to approximately 3 yearsDescription: Disability progression assessed by 20% worsening from baseline over 3 years on T25W
Measure: Timed 25-foot Walk (T25W) Time: Up to approximately 3 yearsDescription: Change from baseline in the time in seconds needed to complete test activity
Measure: Nine-hole Peg Test (9-HPT) Time: Up to approximately 3 yearsDescription: Change from baseline in EDSS score (0-10) yearly and at 3 years
Measure: Expanded Disability Status Scale (EDSS) Time: Up to approximately 3 yearsDescription: An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a pre-existing condition) should be considered an AE.
Measure: Adverse Events (AEs) Time: Up to approximately 3 years8 Role of Microglial Activation and Norepinephrine Transporter Abnormalities in Pathogenesis of MS-related Fatigue
The overarching aim is to assess the role of microglial activation and norepinephrine transporter binding in pathogenesis of MS-related fatigue, using novel Positron Emission Tomography (PET) radiotracers, [F-18]PBR06 and [C-11]MRB. Specific Aims: Specific Aim 1: To determine the relationship of cerebral microglial activation, as assessed by [F-18]PBR06 PET, with MS-related fatigue. Specific Aim 2: To determine the relationship of norepinephrine transporter (NET) binding, as assessed by [C-11]MRB PET, with MS-related fatigue. Specific Aim 3: To determine the relationship of microglial activation and NET binding, with grey matter pathology (lesion load and brain atrophy) assessed using 7T MRI, and evaluate their independent contribution in development of MS-related fatigue.
NCT04144257 Multiple Sclerosis Drug: [F-18]PBR06 Drug: [C-11]Methylreboxetine MeSH:Multiple Sclerosis Fatigue
HPO:Fatigue
Clinical Data The following non-imaging, clinical data will be obtained: Modified fatigue Impact Scale (MFIS) Fatigue Severity Status Scale (FSSS) Expanded Disability Status Scale (EDSS) Timed 25-feet walk (T25W) MS Functional Composite (MSFC) Symbol digit modalities test (SDMT) MSQOL-54 scale (QOL) Pittsburgh Sleep Quality Index (PSQI) Beck's Depression Inventory (BDI) Center for Epidemiological Studies-Depression Scale (CES-D) Hospital Anxiety and Depression Scale (HADS) --- T25W ---
Primary Outcomes
Description: PET outcome measure
Measure: Standardized Uptake Value (SUV)/Standardized Uptake Value Ratio (SUVR) Time: BaselineSecondary Outcomes
Description: Clinical outcome measure; Physical subscale range: 0-36; Cognitive subscale range: 0-40; Psychosocial subscale range: 0-8; Total MFIS Score scale range (Subscales Summed): 0-84; Higher values represent worse outcomes.
Measure: Modified Fatigue Impact Scale (MFIS) Time: BaselineDescription: PET outcome measure
Measure: Binding Potential (BPnd) Time: BaselineDescription: MRI outcome measure
Measure: MRI grey matter lesional load/brain atrophy Time: BaselineDescription: PET outcome measure
Measure: Tissue Volume of distribution (Vt)/Distribution Volume Ratios (DVR) Time: BaselineDescription: MRI outcome measure
Measure: MRI global/regional volumetrics Time: Baseline9 Open-label, Observational, Prospective, 9-month Study to Assess the Efficacy of Ofatumumab on Microglia in Patients With Relapsing Forms of Multiple Sclerosis
We aim to assess the effect of Ofatumumab on microglial activation using [F-18]PBR06 PET in MS patients in relation to changes in serum markers, MRI abnormalities and clinical impairment longitudinally over 9 months. Specific Aims: Specific Aim 1: To determine the effect of Ofatumumab on microglial activation in MS over 9 months. Specific Aim 2: To determine the time course of effect of Ofatumumab on microglial activation and its relationship with peripheral B-cell depletion, serum neurofilament light (sNfL) chain and glial-fibrillary acid protein (GFAP) levels and other serum biomarkers Specific Aim 3: To determine the relationship of PET changes following Ofatumumab initiation with 3T MRI changes and clinical parameters.
NCT04510220 Relapsing Multiple Sclerosis Drug: Ofatumumab Drug: [F-18]PBR06 MeSH:Multiple Sclerosis Sclerosis
Clinical Data: The following non-imaging, clinical data will be obtained: Expanded Disability Status Scale (EDSS), Timed 25-feet walk (T25W), 9-Hole Peg Test (9HPT), Four component MS Functional Composite (MSFC-4), Symbol-Digit Modality test (SDMT), cognitive and symptom questionnaires, vision testing, Levels of serum biomarkers. --- T25W ---
Primary Outcomes
Description: The primary endpoint of the study will be the change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements at early and late time-points (5, 28, 90 and 273 days) as compared to baseline.
Measure: Effect of Ofatumumab on microglial activity Time: Baseline to 9 monthsSecondary Outcomes
Description: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the peripheral CD19 counts at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and CD19 counts Time: Baseline to 9 monthsDescription: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the serum glial fibrillary acid protein (GFAP) level measurements at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and glial fibrillary acid protein (GFAP) Time: Baseline to 9 monthsDescription: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in the serum neurofilament light chain levels at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and neurofilament light chain Time: Baseline to 9 monthsDescription: Association of change in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in MRI -based brain volume (in ml) measurements at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and MRI-based brain atrophy changes Time: Baseline to 9 monthsDescription: Association of changes in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in disease severity (measured using expanded disability status scale or EDSS) at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and physical disability Time: Baseline to 9 monthsDescription: Association of changes in regional microglial activity in the brain using standardized uptake value ratio (SUVR) measurements with changes in severity of cognitive impairment (measured using symbol digit modality test or SDMT) at 5, 28, 90 and 273 days as compared to baseline. We will calculate the change from day 0 to each of the other time points for each of the measures, and we will estimate the correlation between the changes using Pearson's correlation coefficient.
Measure: Relationship between changes in Microglial activity and cognitive disability Time: Baseline to 9 months