SNPMiner Trials by Shray Alag


SNPMiner Trials: Mutation Report


Report for Mutation T25W

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 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: Sclerosis Multiple Sclerosis Neoplasm Metastasis Multiple Sclerosis, Chronic Progressive

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

2 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 Sclerosis Behavioral: Home-based Exercise
MeSH: Sclerosis Multiple 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

3 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: Sclerosis Multiple 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

4 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: Sclerosis Multiple 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

5 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: Disease 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)


HPO Nodes