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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HD091155-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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Cognitive impairment is highly prevalent, poorly-managed, and disabling in persons with MS and exercise training might represent a promising approach to manage this symptom of the disease. The proposed study aims to examine the effects of 3-months of supervised, progressive (both intensity and duration) treadmill walking exercise training (designed based on pilot work and American College of Sports Medicine guidelines) compared with an active control condition (i.e., stretching-and-toning activities) on cognitive processing speed and functional MRI outcomes in 88 cognitively-impaired persons with MS. This study is critical for providing evidence supporting treadmill walking exercise training as a behavioral approach for managing slowed cognitive processing speed (i.e., the most common MS-related cognitive impairment) and improving brain health in persons with MS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treadmill Walking Exercise Training | Experimental | This condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test. The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. |
|
| Stretching-and-Toning Exercise Training | Active Comparator | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Treadmill Walking Exercise Training | Behavioral | 12-weeks of supervised, progressive treadmill walking exercise training |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive Processing Speed | Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed) | Baseline, Follow-up (up to 14 weeks) |
| Thalamocortical Resting-State Functional Connectivity Region 1 | Change in functional connectivity between the thalamus and left superior medial gyrus based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity. | Follow-up at 12-weeks minus baseline |
| Change in Thalamocortical Resting State Functional Connectivity Region 2 | Resting-state functional connectivity between the thalamus and left putamen based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity. | Follow-up at 12-weeks minus baseline |
| Measure | Description | Time Frame |
|---|---|---|
| 3-second Paced Auditory Serial Addition Test (PASAT) | The 3-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The total score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition | Baseline, Follow-up (up to 14-weeks) |
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All participants will:
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| Name | Affiliation | Role |
|---|---|---|
| Brian M Sandroff, PhD | Kessler Foundation | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kessler Foundation | West Orange | New Jersey | 07052 | United States |
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N=4 participants who were enrolled into the study subsequently dropped out prior to random assignment. Thus, 43 participants were enrolled into the study and 39 participants were randomly assigned into the study arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treadmill Walking Exercise Training | This condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test. The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training |
| FG001 | Stretching-and-Toning Exercise Training | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
2 participants who were enrolled into the study dropped out prior to completing baseline measures
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| ID | Title | Description |
|---|---|---|
| BG000 | Treadmill Walking Exercise Training | This condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test. The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cognitive Processing Speed | Raw (Total) Score from the Symbol Digit Modalities Test (0-110; higher scores indicate faster cognitive processing speed) | Posted | Mean | Standard Deviation | Raw Score | Baseline, Follow-up (up to 14 weeks) |
|
12-weeks
The number of participants at risk for adverse events reflects those who were randomly assigned into the conditions (i.e., n=39).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treadmill Walking Exercise Training | This condition will include 3-months of supervised, progressive light, moderate, and vigorous intensity treadmill walking exercise training based on ACSM guidelines for maximizing adaptations with exercise training. Exercise intensities will be prescribed based on percent oxygen consumption reserve (% VO2R) using values derived from the baseline graded exercise test. The exercise training itself will be led by trained exercise leaders who are not involved in the collection of outcome assessments. At the outset of each session, participants will be fitted with a Polar HR Monitor (Oy, Finland), and HR will be monitored continuously throughout each session. Each session will begin with a 5-10 min warm-up, followed by the exercise; the target heart rate reserve (HRR) range associated with the VO2R range will be maintained for as long as possible during each exercise period. This will be followed by a 5-10 min cool-down. Treadmill Walking Exercise Training: 12-weeks of supervised, progressive treadmill walking exercise training |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Minor injury | General disorders | Non-systematic Assessment | 5 participants experienced minor injuries due to falls that occurred outside of the intervention |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brian Sandroff, PhD | Kessler Foundation | 973-965-6649 | bsandroff@kesslerfoundation.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 21, 2020 | May 2, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | May 1, 2023 | May 2, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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Participants will be unaware if the treadmill walking exercise training or stretching-and-toning conditions represent the experimental or control conditions; outcome assessors will be treatment-blinded; MRI data analysts will be blinded to condition
| Stretching-and-Toning Exercise Training | Behavioral | 12-weeks of supervised, progressive stretching-and-toning exercise training |
|
| 2-second Paced Auditory Serial Addition Test (PASAT) | The 2-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The raw score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition. | Baseline, Follow-up (up to 14-weeks) |
| Pattern Comparison Test | The Pattern Comparison Test is a neuropsychological test of cognitive processing speed wherein participants are asked to specify whether or not two patterns are the same or different. The primary outcome is the total number of correct answers provided by the participant across two 20-second trials. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognitive processing speed. | Baseline, Follow-up (up to 14-weeks) |
| Community Integration Questionnaire | The Community Integration Questionnaire is a patient-reported measure of community participation. The minimum score is 0 and the maximum score is 31, with higher scores reflecting better community participation. | Baseline, Follow-up (up to 14-weeks) |
| Lawton-Brody Instrumental Activities of Daily Living | The Lawton-Brody Instrumental Activities of Daily Living is a patient-reported measure of the ability to perform instrumental activities of daily living. The minimum score is 0 and the maximum score is 8, with higher scores reflecting a better ability to complete instrumental activities of daily living. | Baseline, Follow-up (up to 14-weeks) |
| Multiple Sclerosis Impact Scale-29 Physical Subscale | The Multiple Sclerosis Impact Scale-29 is a patient-reported measure of the impact of multiple sclerosis on physical and mental domains. In this outcome measure, the physical subscale is the component of interest. The minimum score is 0 and the maximum score is 100, with higher scores reflecting greater impact of MS on physical outcomes. | Baseline, Follow-up (up to 14-weeks) |
| Timed 25-foot Walk | The timed 25-foot walk is a neuroperformance outcome where participants are asked to walk as quickly and as safely as possible over a 25-foot course free of debris. The primary outcome is the time to walk 25 feet - averaged across two trials. Higher scores reflect slower walking speed and lower scores reflect faster walking speed. | Baseline, Follow-up (up to 14-weeks) |
| BG001 | Stretching-and-Toning Exercise Training | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Education | Mean | Standard Deviation | Years |
|
| Expanded Disability Status Scale | This is an ordinal scale of MS disability ranging from 0 (i.e., no disability) to 10 (i.e., death due to MS) that is administered by a Neurostatus-certified examiner. Higher scores indicate worse MS disability. | Median | Full Range | units on a scale |
|
| Disease Duration | Mean | Standard Deviation | years |
|
| MS Phenotype | Count of Participants | Participants |
|
| Symbol Digit Modalities Test z-score | This baseline measure provides an index of MS-related cognitive processing speed impairment using regression-based normative data that accounts for age, sex, and education. A z-score of 0 indicates no impairment relative to healthy controls, accounting for age, sex, and education. Lower z-scores indicate worse MS-related cognitive processing speed impairment. | Mean | Standard Deviation | z-score |
|
| OG001 | Stretching-and-Toning Exercise Training | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training |
|
|
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| Primary | Thalamocortical Resting-State Functional Connectivity Region 1 | Change in functional connectivity between the thalamus and left superior medial gyrus based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity. | N=3 participants did not complete MRI at follow-up (12-weeks) | Posted | Mean | Standard Deviation | z-score | Follow-up at 12-weeks minus baseline |
|
|
|
|
| Primary | Change in Thalamocortical Resting State Functional Connectivity Region 2 | Resting-state functional connectivity between the thalamus and left putamen based on fMRI. As this outcome measure reflects changes in resting-state functional connectivity, positive z-scores indicate increased connectivity and negative z-scores indicate decreased connectivity. A z-score of 0 reflects no change in resting-state functional connectivity. | N=3 participants did not complete MRI at follow-up (12-weeks) | Posted | Mean | Standard Deviation | z-score | Follow-up at 12-weeks minus baseline |
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| Secondary | 3-second Paced Auditory Serial Addition Test (PASAT) | The 3-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The total score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
|
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|
|
| Secondary | 2-second Paced Auditory Serial Addition Test (PASAT) | The 2-second PASAT is a neuropsychological test of working memory, attention, and cognitive processing speed. The raw score is the total number of correct answers provided by the participant. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognition. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
|
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|
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| Secondary | Pattern Comparison Test | The Pattern Comparison Test is a neuropsychological test of cognitive processing speed wherein participants are asked to specify whether or not two patterns are the same or different. The primary outcome is the total number of correct answers provided by the participant across two 20-second trials. The minimum score is 0 and the maximum score is 60. Higher scores reflect better cognitive processing speed. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
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| Secondary | Community Integration Questionnaire | The Community Integration Questionnaire is a patient-reported measure of community participation. The minimum score is 0 and the maximum score is 31, with higher scores reflecting better community participation. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
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| Secondary | Lawton-Brody Instrumental Activities of Daily Living | The Lawton-Brody Instrumental Activities of Daily Living is a patient-reported measure of the ability to perform instrumental activities of daily living. The minimum score is 0 and the maximum score is 8, with higher scores reflecting a better ability to complete instrumental activities of daily living. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
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| Secondary | Multiple Sclerosis Impact Scale-29 Physical Subscale | The Multiple Sclerosis Impact Scale-29 is a patient-reported measure of the impact of multiple sclerosis on physical and mental domains. In this outcome measure, the physical subscale is the component of interest. The minimum score is 0 and the maximum score is 100, with higher scores reflecting greater impact of MS on physical outcomes. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Follow-up (up to 14-weeks) |
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| Secondary | Timed 25-foot Walk | The timed 25-foot walk is a neuroperformance outcome where participants are asked to walk as quickly and as safely as possible over a 25-foot course free of debris. The primary outcome is the time to walk 25 feet - averaged across two trials. Higher scores reflect slower walking speed and lower scores reflect faster walking speed. | Posted | Mean | Standard Deviation | Seconds | Baseline, Follow-up (up to 14-weeks) |
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|
|
|
| 0 |
| 19 |
| 0 |
| 19 |
| 8 |
| 19 |
| EG001 | Stretching-and-Toning Exercise Training | The active, non-aerobic exercise condition will involve stretching-and-toning activities using the same frequency and duration of the treadmill walking exercise condition. These activities will be based on a manual provided by the National Multiple Sclerosis Society and sessions will be led by trained exercise leaders who are not involved in the collection of outcome assessments. Activities will target the head/neck, shoulder, elbow/forearm, hand/wrist, trunk/hip, ankle/foot. The progression of activities over the 3-month period will involve performing additional exercises and sets along with using progressively thicker elastic resistance bands that provide minimal resistance. Each session is designed to last up to 60 minutes in total. Each session will begin with a warm-up of up to 10 minutes, followed by stretching-and-toning (following the same duration as the treadmill walking exercise training condition) activities, and a cool-down of up to 10 minutes. Stretching-and-Toning Exercise Training: 12-weeks of supervised, progressive stretching-and-toning exercise training | 0 | 20 | 0 | 20 | 1 | 20 |
|
| Temporary illness | General disorders | Non-systematic Assessment |
|
| COVID-19 | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Minor Skin Rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |