Multiple SclerosisBRAVe-MSNCT05433103
Blood Flow Restriction And Veterans With MS
A study testing Low-Load Exercise with Blood Flow Restriction in people with Multiple Sclerosis, run by VA Office of Research and Development at 1 site in United States.
Trial summary
There currently is a lack of evidence to support exercise interventions in people with advanced disability due to MS (i.e., need assistance to walk or use a wheelchair). This project proposes to study a strength training program using blood flow restriction (BFR) in people with advanced disability due to MS. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Low-Load Exercise with Blood Flow Restriction
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jan 2023to 31 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of MS
- Age 18-75
- Patient Determined Disease Steps (PDDS) 4 to 7
- PDDS 4: Early cane: I use a cane or a single crutch or some other form of support (such as touching a wall or leaning on someone's arm) for walking all the time or part of the time, especially when walking outside. I think I can walk 25 feet in 20 seconds without a cane or crutch. I always need some assistance (cane or crutch) if I want to walk as far as three blocks.
- PDDS 5: Late cane: To be able to walk 25 feet, I have to have a cane, crutch, or someone to hold onto. I can get around the house or other buildings by holding onto furniture or touching the walls for support. I may use a scooter or wheelchair if I want to go greater distances.
- PDDS 6: Bilateral support: To be able to walk as far as 25 feet I must have two canes or crutches or a walker. I may use a scooter or wheelchair for longer distances.
- PDDS 7: Wheelchair/scooter: My main form of mobility is a wheelchair. I may be able to stand and/or take one or two steps, but I can't walk 25 feet, even with crutches or a walker.
Who cannot join
- PDDS 8: Unable to sit in a wheelchair for more than one hour.
- PDDS 3 or less: MS does not interfere with my activities, especially my walking. I can work a full day, but athletic or physically demanding activities are more difficult than they used to be. I usually don't need a can or other assistance to walk, but I might need some assistance during an attack.
- Moderate to Severe cognitive impairment as identified by the St. Louis University Mental Status Exam Score <=20
- History of deep venous thrombosis/pulmonary embolism, peripheral vascular disease, thrombophilia, clotting disorders
- Systolic BP >= 180 mmHg or Diastolic BP >= 110 mmHg.
- Any comorbid conditions or pain that substantially affects physical function or would interfere with the participant's ability to safely complete rehabilitation (e.g. neurologic, vascular, cardiac problems, orthopedic, or ongoing medical treatments) as determined by a neurologist or physical therapist
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- Patient report of easy bruising
- Severe lower extremity spasticity as defined as Modified Ashworth scale >2.
- Engaged in progressive resistance training program currently or in the previous 2 months prior to enrollment.
- Use of blood flow restriction currently or in the previous 2 months prior to enrollment.
- MS-related exacerbation or changes to their disease-modifying drug therapy in the month prior to enrollment.
- Inability to tolerate pressure cuff during baseline assessment.
- Unable to perform seated leg press exercise or no against gravity knee extension strength in at least one limb.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Rocky Mountain Regional VA Medical Center, Aurora, CO
Aurora, Colorado, 80045-7211
Mark M Manago, PT, 303-399-8020, mark.manago@va.gov
Eliza A Biondi, (303) 724-9170, eliza.biondi@va.gov
About this study
Official title: Low-Load Resistance Training With Blood Flow Restriction in People With Multiple Sclerosis and Advanced Disability: A Randomized Control Trial
There currently is a lack of evidence to support exercise interventions in people with advanced disability due to MS (i.e., need assistance to walk or use a wheelchair). This project proposes to study a strength training program using blood flow restriction (BFR) in people with advanced disability due to MS. BFR uses a device that partially blocks blood flow to the exercising limb and causes a response in the muscle which can replicate the effects of high-intensity training using much lower intensities. This is ideal for people with MS who have advanced disability, as they often cannot tolerate higher intensity exercise due to severe weakness and fatigue. By studying BFR training in people with advanced disability due to MS, the investigators hope to help improve strength, mobility, fatigue, and quality of life in people with MS. This study will target enrollment of Veterans with MS, who tend to have more advanced disability than non-Veterans with MS.
Read the detailed description
Multiple Sclerosis (MS) is a chronic neurological disorder affecting about 1 million Americans. Among the many MS symptoms, muscle weakness is among the most common, contributes to decreased mobility, and worsens as disability advances. While there is strong evidence that moderate-to-high intensity resistance training improves muscle strength in people with MS and low disability, there is little evidence evaluating resistance training in people with advanced disability due to MS (i.e., those who need assistance to walk or use a wheelchair). People with advanced disability due to MS require unique approaches to resistance training as they often cannot tolerate higher intensity exercise because of severe weakness and fatigue. Blood flow restriction (BFR) has the potential to address these issues. With BFR, resistance training at low intensities has been shown to be as effective as high intensity training without BFR at increasing muscle strength and hypertrophy in people with a variety of musculoskeletal conditions. The preliminary data supports the safety, feasibility, and tolerance of BFR resistance training in people with advanced disability due to MS. The objective of the currently proposed study is to evaluate the efficacy of low-load resistance training with BFR on muscle strength, mobility, and fatigue in people with advanced disability due to MS.
This proposed Phase II clinical trial will target enrollment of Veterans with MS, who would often have more severe symptoms, worse mobility, and more advanced disability compared to non-Veterans with MS. The study hopes to address a crucial gap that is highly relevant for Veterans with MS:
interventions to improve mobility and optimize function for those with advanced disability. Fifty-eight participants with MS and advanced disability will be randomized (1:1) to low-load resistance training with BFR (experimental) or without BFR (control). Resistance training will target knee and hip extension, knee and hip flexion, and ankle plantarflexion 2x/week for 10 weeks. A blinded assessor will collect outcomes at baseline, post- intervention (primary endpoint), and after 8 weeks of follow-up. The Study Aims are to determine between-group differences in 1) Muscle health: quadriceps strength (primary outcome) and muscle morphology (thickness and echogenicity); 2) Mobility: 30-Second Sit-to-Stand; and 3) Self-reported fatigue: Modified Fatigue Impact Scale. The investigators hypothesize that the experimental group will have significantly greater improvements in muscle strength and thickness, mobility, and self-reported fatigue compared to the control group. The long-term goal of this research is to develop clinically feasible exercise interventions for people with advanced disability due to MS that can improve participation, quality of life, and disability.
- Conditions
- Multiple Sclerosis
- Being tested
- Low-Load Exercise with Blood Flow Restriction, Low-Load Exercise Control Group
- Keywords
- Multiple Sclerosis, Blood Flow Restriction, Exercise, Low-load resistance training
- Medical subject headings
- Multiple Sclerosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low-Load Exercise with Blood Flow RestrictionOther
Also called BFR
Participants in the BFR group will attend a 10-week, twice weekly intervention exercise session combining low-load resistance training with at least 60% blood flow occlusion. Standard education regarding the importance of exercise for people with MS will also be provided. All participants will also be asked to practice a home exercise program focusing on functional tasks one time a week.
Low-Load Exercise Control GroupOther
Also called Control
Participants in the Control group will attend a 10-week, twice weekly intervention exercise session combining low-load resistance training. Standard education regarding the importance of exercise for people with MS will also be provided. All participants will also be asked to practice a home exercise program focusing on functional tasks one time a week.
| Study group | Role | What they receive |
|---|---|---|
| Low-Load Exercise with Blood Flow Restriction | Experimental | The BFR intervention will combine low-load resistance training with between 60%-80% blood flow occlusion under the supervision of a licensed physical therapist. Receives: Other: Low-Load Exercise with Blood Flow Restriction |
| Low-Load Exercise Control | Active comparator | The control group with consist only of low-load resistance training under the supervision of a licensed physical therapist. Receives: Other: Low-Load Exercise Control Group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quadriceps muscle strength
Quadriceps muscle strength measured using dynamometry.
Measured: Change in muscle strength between Baseline (Week 0) and Primary Endpoint (Week 11)
Secondary outcomes (3)
Muscle morphology
Muscle morphology is measured using ultrasonography to determine thickness and echogenicity.
Measured: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
30-second sit to stand
The number of times the participant can transition from sitting to standing in 30 seconds.
Measured: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
Modified Fatigue Impact Scale
A 21-item questionnaire describing how fatigue may affect a person. Scores range from 0 to 84 with higher scores indicating more fatigue.
Measured: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2022
- Study start1 Jan 2023
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized control trial with two groups.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Mark M Manago, PT, Principal investigator, Rocky Mountain Regional VA Medical Center, Aurora, CO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05433103
- Sponsor's protocol ID
- F4242-W
- Acronym
- BRAVe-MS
- Status last verified
- Feb 2026
- First submitted
- 21 Jun 2022
- Last updated
- 23 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Manago MM, Will R, Strahler T, Van Valkenburgh L, Harris-Love MO, Forster JE, Cameron M, Christiansen CL. Blood Flow Restriction and Veterans With Multiple Sclerosis and Advanced Disability: Protocol for a Randomized Controlled Trial. Phys Ther. 2024 Jun 4;104(6):pzae037. doi: 10.1093/ptj/pzae037.
PubMed 38452199
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low-Load Resistance Training With Blood Flow Restriction in People With Multiple Sclerosis and Advanced Disability: A Randomized Control Trial
- ClinicalTrials.gov ID
- NCT05433103
- Acronym / sponsor ID
- BRAVe-MS / F4242-W
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Blood Flow Restriction, Exercise, Low-load resistance training
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 27 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There currently is a lack of evidence to support exercise interventions in people with advanced disability due to MS (i.e., need assistance to walk or use a wheelchair). This project proposes to study a strength training program using blood flow restriction (BFR) in people with advanced disability due to MS. BFR uses a device that partially blocks blood flow to the exercising limb and causes a response in the muscle which can replicate the effects of high-intensity training using much lower intensities. This is ideal for people with MS who have advanced disability, as they often cannot tolerate higher intensity exercise due to severe weakness and fatigue. By studying BFR training in people with advanced disability due to MS, the investigators hope to help improve strength, mobility, fatigue, and quality of life in people with MS. This study will target enrollment of Veterans with MS, who tend to have more advanced disability than non-Veterans with MS.
Detailed description
Multiple Sclerosis (MS) is a chronic neurological disorder affecting about 1 million Americans. Among the many MS symptoms, muscle weakness is among the most common, contributes to decreased mobility, and worsens as disability advances. While there is strong evidence that moderate-to-high intensity resistance training improves muscle strength in people with MS and low disability, there is little evidence evaluating resistance training in people with advanced disability due to MS (i.e., those who need assistance to walk or use a wheelchair). People with advanced disability due to MS require unique approaches to resistance training as they often cannot tolerate higher intensity exercise because of severe weakness and fatigue. Blood flow restriction (BFR) has the potential to address these issues. With BFR, resistance training at low intensities has been shown to be as effective as high intensity training without BFR at increasing muscle strength and hypertrophy in people with a variety of musculoskeletal conditions. The preliminary data supports the safety, feasibility, and tolerance of BFR resistance training in people with advanced disability due to MS. The objective of the currently proposed study is to evaluate the efficacy of low-load resistance training with BFR on muscle strength, mobility, and fatigue in people with advanced disability due to MS.
This proposed Phase II clinical trial will target enrollment of Veterans with MS, who would often have more severe symptoms, worse mobility, and more advanced disability compared to non-Veterans with MS. The study hopes to address a crucial gap that is highly relevant for Veterans with MS:
interventions to improve mobility and optimize function for those with advanced disability. Fifty-eight participants with MS and advanced disability will be randomized (1:1) to low-load resistance training with BFR (experimental) or without BFR (control). Resistance training will target knee and hip extension, knee and hip flexion, and ankle plantarflexion 2x/week for 10 weeks. A blinded assessor will collect outcomes at baseline, post- intervention (primary endpoint), and after 8 weeks of follow-up. The Study Aims are to determine between-group differences in 1) Muscle health: quadriceps strength (primary outcome) and muscle morphology (thickness and echogenicity); 2) Mobility: 30-Second Sit-to-Stand; and 3) Self-reported fatigue: Modified Fatigue Impact Scale. The investigators hypothesize that the experimental group will have significantly greater improvements in muscle strength and thickness, mobility, and self-reported fatigue compared to the control group. The long-term goal of this research is to develop clinically feasible exercise interventions for people with advanced disability due to MS that can improve participation, quality of life, and disability.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized control trial with two groups.
| Arm | Type | Receives |
|---|---|---|
| Low-Load Exercise with Blood Flow Restriction | Experimental | Other: Low-Load Exercise with Blood Flow RestrictionThe BFR intervention will combine low-load resistance training with between 60%-80% blood flow occlusion under the supervision of a licensed physical therapist. |
| Low-Load Exercise Control | Active comparator | Other: Low-Load Exercise Control GroupThe control group with consist only of low-load resistance training under the supervision of a licensed physical therapist. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed diagnosis of MS
- Age 18-75
- Patient Determined Disease Steps (PDDS) 4 to 7
Key exclusion criteria (13 listed)
- PDDS 8: Unable to sit in a wheelchair for more than one hour.
- PDDS 3 or less: MS does not interfere with my activities, especially my walking. I can work a full day, but athletic or physically demanding activities are more difficult than they used to be. I usually don't need a can or other assistance to walk, but I might need some assistance during an attack.
- Moderate to Severe cognitive impairment as identified by the St. Louis University Mental Status Exam Score <=20
- History of deep venous thrombosis/pulmonary embolism, peripheral vascular disease, thrombophilia, clotting disorders
- Systolic BP >= 180 mmHg or Diastolic BP >= 110 mmHg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low-Load Exercise with Blood Flow RestrictionAlso: BFRParticipants in the BFR group will attend a 10-week, twice weekly intervention exercise session combining low-load resistance training with at least 60% blood flow occlusion. Standard education regarding the importance of exercise for people with MS will also be provided. All participants will also be asked to practice a home exercise program focusing on functional tasks one time a week. | Other | Low-Load Exercise with Blood Flow Restriction |
| Low-Load Exercise Control GroupAlso: ControlParticipants in the Control group will attend a 10-week, twice weekly intervention exercise session combining low-load resistance training. Standard education regarding the importance of exercise for people with MS will also be provided. All participants will also be asked to practice a home exercise program focusing on functional tasks one time a week. | Other | Low-Load Exercise Control |
Primary outcome
Quadriceps muscle strength
Time frame: Change in muscle strength between Baseline (Week 0) and Primary Endpoint (Week 11)
Quadriceps muscle strength measured using dynamometry.
3 secondary outcomes
Muscle morphology
Time frame: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
30-second sit to stand
Time frame: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
Modified Fatigue Impact Scale
Time frame: Change between Baseline (Week 0) and Primary Endpoint (Week 11)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2026.
- Derived from this study: PubMed 38452199Manago MM, Will R, Strahler T, Van Valkenburgh L, Harris-Love MO, Forster JE, Cameron M, Christiansen CL. Blood Flow Restriction and Veterans With Multiple Sclerosis and Advanced Disability: Protocol for a Randomized Controlled Trial. Phys Ther. 2024 Jun 4;104(6):pzae037. doi: 10.1093/ptj/pzae037.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Mark M Manago, PT principal investigator
Rocky Mountain Regional VA Medical Center, Aurora, CO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low-Load Exercise with Blood Flow Restriction in people with Multiple Sclerosis, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mark M Manago, PT ((303) 399-8020, mark.manago@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quadriceps muscle strength (time frame: Change in muscle strength between Baseline (Week 0) and Primary Endpoint (Week 11)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05433103, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026; AzTrials last refreshed its copy on 30 Oct 2026.