SNPMiner Trials by Shray Alag


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Report for Mutation T25W

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 8 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 Sc 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 months

Secondary 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 months

Description: 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 Months

Description: Spasticity will be assessed with the modified ashworth scale.

Measure: Spasticity

Time: 3 Months

2 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 months

Secondary 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 Months

Description: 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 months

Description: 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 Months

3 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 relapse throughout the double-blind period (up to approximately 38 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 24

Description: 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 24

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 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 years)

Measure: Annualized Relapse Rate

Time: From Baseline until 12 weeks after last dose of satralizumab (up to approximately 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 6.75 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 38 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 6.75 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 months

Secondary Outcomes

Description: brief, standardized, quantitative test of upper extremity

Measure: 9-Hole Peg Test

Time: administered at baseline, one month, 6 months, and 12 months

Description: measures cognitive processing speed and working memory

Measure: Symbol Digit Modalities Test

Time: administered at baseline, one month, 6 months, and 12 months

Description: 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 months

Description: 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 months

Description: 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 months

5 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 Phase 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 drug

Measure: 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 Phase 2 dose of ATA188 monotherapy

Time: Day 1 to Day 35 of Cycle 1 for each participant in dose escalation phase (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 drug

Secondary 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 drug

Description: 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 drug

Description: 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 drug

Description: 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 drug

6 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 months

Secondary Outcomes

Description: PET outcome measure change at 6 months from baseline

Measure: PET Uptake/Standardized uptake value ratio (SUVR) change

Time: baseline and 6 months

Description: MRI outcome measure change at 18 months from baseline

Measure: T2/FLAIR lesion load change

Time: baseline and 18 months

Description: MRI outcome measure change at 18 months from baseline

Measure: Whole brain/deep gray matter atrophy change

Time: baseline and 18 months

Description: 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 months

Description: Clinical outcome measure change at 18 months from baseline

Measure: Timed 25-foot walk (T25FW) change

Time: baseline and 18 months

Description: 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 months

Description: Clinical outcome measure change at 18 months from baseline

Measure: Minimal Assessment of Cognitive Function in MS (MACFIMS) change

Time: baseline and 18 months

7 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. If commercial drug is not available at the end of the study, subjects may be started on another medication as determined by their individual treating physician. 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 years

Secondary 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 years

Description: 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 years

Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with an increase in raw score of ≥ 3 points from baseline

Time: Up to approximately 3 years

Description: Symbol Digit Modalities Test

Measure: Proportion of subjects with a decrease in raw score of ≥ 3 points from baseline

Time: Up to approximately 3 years

Description: The SDMT is a measure of cognitive processing speed

Measure: Change from baseline in Symbol Digit Modalities Test (SMDT)

Time: Up to approximately 3 years

Description: 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 years

Description: Magnetic Resonance Imaging

Measure: Proportion of subjects free of gadolinium enhancing (GdE) lesions over 3 years

Time: Up to approximately 3 years

Description: Magnetic Resonance Imaging

Measure: GdE lesion volume over 3 years

Time: Up to approximately 3 years

Description: 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 years

Description: 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 years

Description: Change is TSQM score over 3 years

Measure: Treatment Satisfaction Questionnaire for Medication (TSQM v1.4)

Time: Up to approximately 3 years

Description: Change in WPAI score over 3 years

Measure: Work Productivity and Activity Impairment-Multiple Sclerosis (WPAI-MS)

Time: Up to approximately 3 years

Description: 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 years

Description: 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 years

Description: 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 years

Description: Change in relapse rate over 3 years

Measure: Annualized relapse rate (ARR)

Time: Up to approximately 3 years

Description: Disability progression assessed by 20% worsening from baseline over 3 years on T25W

Measure: Timed 25-foot Walk (T25W)

Time: Up to approximately 3 years

Description: 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 years

Description: Change from baseline in EDSS score (0-10) yearly and at 3 years

Measure: Expanded Disability Status Scale (EDSS)

Time: Up to approximately 3 years

Description: 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 years

8 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: Baseline

Secondary 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: Baseline

Description: PET outcome measure

Measure: Binding Potential (BPnd)

Time: Baseline

Description: MRI outcome measure

Measure: MRI grey matter lesional load/brain atrophy

Time: Baseline

Description: PET outcome measure

Measure: Tissue Volume of distribution (Vt)/Distribution Volume Ratios (DVR)

Time: Baseline

Description: MRI outcome measure

Measure: MRI global/regional volumetrics

Time: Baseline


HPO Nodes


Fatigue
Genes 389
MPL RPL18 BIRC3 OPA1 JAK2 POU2AF1 TET2 ATRX POU1F1 SLC40A1 SQSTM1 PAX8 SCNN1B KIT SLC25A11 PON2 COQ2 PROKR2 PIGA IRF2BP2 OPTN HMGCL MMACHC HBA1 PODXL ERCC4 SLC2A10 PREPL RPL15 SCNN1G FOXA2 ADA2 RPS7 FUS SYNJ1 IL12B SLC11A1 DYSF MEN1 CDH23 BRCA2 HLA-B TRNF DMD PNPLA8 TBL1XR1 FIP1L1 LHX3 BCOR HLA-DPB1 ATP13A2 BCR TNXB DUOX2 IL10 COL5A1 GCK AIP BMPR1A IL12A-AS1 SPIB NABP1 MC2R CALR PHKG2 TSC1 MST1 FH RPL31 CCND1 TMEM127 ARMC5 RUNX1 DNAJC6 NUMA1 AIP RPS26 SDHA ELANE RPS27 IL12RB1 TCF3 ND5 MMEL1 VCP SMAD3 CDKN2A SOX2 MET VHL RPL11 BLNK IGH TXNRD2 TWNK FOXP1 HFE TRNH PMS2 SERPINA6 CD79B PROP1 FGFR1 IYD KCNQ2 NNT TSHR SLC26A4 TRNL1 STAT6 NKX2-1 POLG CPT1A ANG KRAS FGF23 CCDC78 VHL TSHR DBH POU1F1 VPS13A KRAS HNRNPA1 MSH2 CFAP410 PFN1 NLRP3 GATA2 ATM JAK2 TAZ C9ORF72 DUOXA2 TRNS1 SDHD CHCHD10 GATA1 NPM1 RPS20 USP8 MPL HAVCR2 COL1A1 TPO TREM2 PTPN22 FTL SCN2A KIT PRKAR1A COX1 HESX1 STAR RPL5 MRAP FOXE1 TRNW COX3 DAO GPR101 LHX4 RPL35 TSC2 IL12A KLRC4 KIF1B TGFBR2 BTK HLA-B NKX2-5 COX2 PDGFRA PAX8 RET RRM2B SMAD4 RPS19 ALB BTNL2 NLRC4 SDHA ERBB4 GLA PON3 GLE1 ZBTB16 NEK1 CDC73 ERCC3 PRTN3 TBX19 SLC5A5 STAT5B COL5A2 RPL35A OTX2 BCL10 CCR1 HNF1A PRPH TFR2 UBQLN2 OTX2 PALLD ND4 ERCC2 KCNQ3 MYH7 GNAS WIPF1 SLC26A4 HLA-B CPT2 FAN1 TWNK TRNQ GLT8D1 PROP1 HESX1 PML CTNNB1 SOD1 C1QBP TET2 RARA NR3C1 PDE11A CDH23 AP2S1 HELLPAR TNFSF15 ABCC2 TRNK CFH MDH2 RPL26 CHRND NLRC4 GPR35 HLA-DPA1 TET2 AGK SLC25A26 MYD88 INSR CAV3 SCNN1A SLC18A2 ATXN2 NR3C1 RPS10 BCL2 MATR3 GBA CFI NEFH PIGT ABL1 PRKACA SLC25A4 CD46 LBR CCNF MAX ANXA11 DNM1L IGHM FIG4 TARDBP VAPB TP53 IL12A IL23R MLH3 ND6 STEAP3 ARNT2 ATP13A2 TG ACADM DLST UNC13A PMS1 SDHB STAT3 TNPO3 RPS15A NAGS PTPN22 TK2 ATP7A MLH1 SDHAF2 POLG2 SDHC PON1 RPS29 ERAP1 SDHB MSH6 EPHA4 LHX4 GLI2 SLC18A3 DCTN1 IGH LRRC8A CHMP2B HESX1 TRNS2 BCL6 SDHC PRKAR1A HBA2 IGLL1 PIK3CA PSTPIP1 SCN8A TSHB CTLA4 CD79A PPARGC1A BRCA1 FAS RPL27 ARMC5 ALB SLC12A3 TAF15 WAS PGM1 HLA-DRB1 TLR4 PROP1 STAT4 ERCC5 IKZF1 RPS24 KCNQ1 SOX3 SH2B3 PLEC CCND1 TET2 CDC73 ND1 HNF4A TBK1 NAB2 PIK3R1 IGH PDE8B ALAS2 HLA-DRB1 MEN1 CDH23 EPCAM NLRP3 TCF4 PTPN3 SLC3A1 MMADHC SEMA4A XPA UBAC2 PRRT2 GCH1 C4A DDB2 TSR2 MALT1 PALB2 PHKA2 MEFV SOX3 RPS17 IRF5 POMGNT1 XPC CPT2 RPS28 EPOR KIF23 KCNE1 JAK2 SMAD3 NFKB2 MLX