Blood Flow Restriction Training for Knee Instability

(BRAINS Trial)

Recruiting at 5 trial locations

Overseen By Natalie Corey

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Caitin Conley

Disqualifiers: Osteochondral lesion, Osteoarthritis, Knee surgery, Inflammatory disorder, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

78 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new type of physical therapy called blood flow restriction training (BFRT) to determine its effectiveness in helping people recover from knee instability. Participants will be divided into two groups: one will receive standard physical therapy with a placebo version of BFRT, while the other will receive the actual BFRT. The trial seeks individuals who have experienced knee instability due to trauma, participate in sports like tennis or skiing weekly, and wish to return to their pre-injury activity levels. As an unphased trial, it provides a unique opportunity to contribute to innovative research that could improve recovery options for active individuals.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have diabetes or uncontrolled hypertension, you are not eligible to participate.

What prior data suggests that blood flow restriction training is safe for knee instability?

Research has shown that blood flow restriction training (BFRT) is generally well-tolerated. In one study, participants using BFRT reported a 93% decrease in daily pain over eight weeks, suggesting it could safely and effectively manage knee problems, such as patellar instability. Another study found that BFRT improved muscle strength and size, aiding recovery and preventing injuries. Although no treatment is entirely risk-free, these findings support BFRT as a promising and safe option for those with knee issues. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about blood flow restriction training (BFRT) for knee instability because it offers a novel approach compared to standard physical therapy. Unlike traditional therapies that focus on high-load exercises to strengthen muscles around the knee, BFRT uses a cuff to partially restrict blood flow, enabling muscle strengthening with much lighter loads. This innovative technique may reduce the stress on joints while still effectively building muscle, which is particularly beneficial for individuals who struggle with heavier exercises due to pain or injury. Additionally, BFRT could lead to quicker rehabilitation times, as it aims to enhance muscle strength and stability more efficiently.

What evidence suggests that blood flow restriction training is effective for knee instability?

Research has shown that blood flow restriction training (BFRT) can aid knee problems. Studies have found that BFRT strengthens muscles and reduces knee pain. In this trial, participants will be divided into two groups: one will receive standard physical therapy with BFRT, with the cuff inflated to 60% occlusion, and the other will receive standard physical therapy with sham BFRT, with the cuff inflated to less than 10% occlusion. For individuals with unstable knees, BFRT has improved knee function, as evidenced by better scores on knee health tests. Additionally, BFRT can promote muscle growth and enhance physical performance. Overall, BFRT appears promising for aiding recovery from knee issues. ^{1 2 6 7 8}

Who Is on the Research Team?

Caitlin Conley, PhD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for individuals aged 14-40 with closed growth plates and traumatic patellar instability, who are active in sports like tennis or skiing at least once a week. They must want to return to their pre-injury activity level. Excluded are those with certain knee conditions, surgeries, high BMI (>35), varicose veins, history of deep vein thrombosis in the family, planned long absences during the trial period, diabetes or uncontrolled hypertension.

Inclusion Criteria

My bones have finished growing, as confirmed by an X-ray.

I want to return to my activity level before my injury.

You are physically active and engage in sports activities like running, tennis, or skiing at least 1-3 times per week.

Exclusion Criteria

My last episode of instability was over 3 months ago.

I have varicose veins or a family history of deep vein thrombosis.

Your body mass index (BMI) is higher than 35, which means you are significantly overweight.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants undergo 8 weeks of either standard physical therapy or standard physical therapy with blood flow restriction training (BFRT).

8 weeks

4 visits (in-person) at weeks 1, 5, 9, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of knee and hip strength, biomechanics, and MRI evaluations.

24 months

3 visits (in-person) at 1 year, 2 years, and additional assessments

What Are the Treatments Tested in This Trial?

Interventions

• Blood Flow Restriction Training

Trial Overview The study tests blood flow restriction training (BFRT) against sham BFRT to see if it helps recovery from patellar instability. Participants will be randomly assigned to either real BFRT or a placebo-like version without actual restriction to compare outcomes.

How Is the Trial Designed?

Group I: Standard Physical Therapy with Sham BFRT Active Control 1 Intervention

Participants will undergo 8 weeks of sham blood flow restriction training with cuff inflated to less than 10% occlusion.

Group II: Standard Physical Therapy with BFRT Active Control 1 Intervention

Participants will undergo 8 weeks of blood flow restriction training with cuff inflated to 60% occlusion.

Blood Flow Restriction Training is already approved in United States, European Union, Japan for the following indications:

Approved in United States as Blood Flow Restriction Training for:

• Rehabilitation after patellar instability
• Post-operative rehabilitation
• Muscle strengthening in patients with injuries or physical limitations

Approved in European Union as Blood Flow Restriction Training for:

• Rehabilitation after orthopedic surgeries
• Muscle strengthening in elderly and arthritic patients
• Post-operative rehabilitation

Approved in Japan as KAATSU Training for:

• Muscle strengthening and hypertrophy
• Rehabilitation after injuries
• Improving muscle endurance

Who Is Running the Clinical Trial?

Caitin Conley

Lead Sponsor

Trials

1

Recruited

80+

Cale Jacobs, PhD

Lead Sponsor

Trials

5

Recruited

140+

Caitlin Conley

Lead Sponsor

Trials

1

Recruited

80+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Blood flow restriction (BFR) training after knee surgery significantly improves the cross-sectional area of the quadriceps muscle, indicating reduced muscle atrophy, based on a systematic review of 11 studies.

However, there were no significant improvements in patient-reported outcomes, and preoperative BFR training did not show clinical benefits, suggesting that while BFR is effective post-surgery, its role before surgery needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Blood Flow Restriction in Patients Undergoing Knee Surgery: A Systematic Review and Meta-analysis. Wengle, L., Migliorini, F., Leroux, T., et al.[2022]

Blood flow restriction (BFR) training is considered a safe and effective method for improving musculoskeletal training outcomes, supported by 25 years of research.

There is a need for standardized, evidence-based protocols for BFR training among health professionals in South Africa to ensure its proper and safe application during rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood flow restriction training in South Africa - a panel discussion. Evans, RW., Ganda, J., van Schalkwyk, L., et al.[2023]

Blood flow restriction low load strength training (BFR-LLST) is feasible for patients recovering from knee cartilage or meniscus repair, with over 84% adherence to the program over 9 weeks.

No serious adverse events were reported during the study, indicating that BFR-LLST is a safe addition to usual care exercise, potentially preventing muscle atrophy without increasing pain or complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: a feasibility study. Jakobsen, TL., Thorborg, K., Fisker, J., et al.[2022]

Blood flow restriction training (BFRT) is generally safe for patients with musculoskeletal disorders, with a systematic review of 19 studies involving 322 participants showing that most did not report adverse events.

While some rare adverse events were noted, such as deep vein thrombosis and rhabdomyolysis, individuals undergoing BFRT did not experience more adverse events compared to those doing regular exercise, indicating its potential as a safe strengthening method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Safety of Blood Flow Restriction Training as a Therapeutic Intervention for Patients With Musculoskeletal Disorders: A Systematic Review. Minniti, MC., Statkevich, AP., Kelly, RL., et al.[2020]

This study is investigating the effectiveness of blood-flow restriction training (BFRT) for improving outcomes in 78 patients with acute patellar dislocations, aiming to enhance recovery and prevent long-term joint issues.

The trial will compare BFRT to a sham treatment alongside standard physical therapy, focusing on patient-reported outcomes, quadriceps strength, and cartilage health, addressing a gap in current rehabilitation practices for patellar instability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood flow Restriction training After patellar INStability (BRAINS Trial). Brightwell, BD., Stone, A., Li, X., et al.[2022]

Combining blood flow restriction (BFR) with low-load resistance training (LLRT) significantly reduced anterior knee pain (AKP) immediately after exercise in a study of 40 males, while LLRT alone did not show similar results.

The LLRT-BFR group maintained pain reduction after a physiotherapy session, suggesting that this method could be an effective preconditioning strategy for rehabilitation of AKP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low load resistance training with blood flow restriction decreases anterior knee pain more than resistance training alone. A pilot randomised controlled trial. Korakakis, V., Whiteley, R., Giakas, G.[2018]

Blood flow restriction training (BFRT) does not show significantly greater efficacy than conventional resistance training for treating knee osteoarthritis, based on a meta-analysis of 5 studies with low to moderate risk of bias.

BFRT may have a lower incidence of adverse events compared to high-load resistance training, suggesting it could be a safer option for patients with knee osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Blood Flow Restriction Training in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis. Wang, HN., Chen, Y., Cheng, L., et al.[2022]

In a study involving 32 adolescents (16 in the BFRT group and 16 in the control group), blood flow restriction training (BFRT) significantly improved isometric knee extension strength at both 3 months post-surgery and at the time of return to sport compared to traditional rehabilitation alone.

The BFRT group also reported better functional outcomes, as indicated by higher Pediatric International Knee Documentation Committee (Pedi-IKDC) scores, demonstrating enhanced patient-reported function after ACL reconstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early- and Late-Stage Benefits of Blood Flow Restriction Training on Knee Strength in Adolescents After Anterior Cruciate Ligament Reconstruction. Roman, DP., Burland, JP., Fredericks, A., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11865041/

Mechanisms of blood flow restriction training for knee pain Besides, a systematic review of KOA showed that BFRT was effective in increasing muscle strength and reducing pain (Pitsillides et al., 2021).

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S136085922400531X

Effectiveness of blood flow restriction (BFR) training on ... Recent data have demonstrated that blood flow restriction (BFR) training may lead to greater hormonal responses during exercise, enhance muscle hypertrophy, ...

3. josr-online.biomedcentral.com josr-online.biomedcentral.com/articles/10.1186/s13018-025-05673-8

The effects of blood flow restriction training on early muscle ... At mid-term follow-up (8–14 weeks), this study found that BFRT exhibited a positive effect on improving knee function (IKDC score) (SMD = 3.70, ...

4. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1524480/full

Impact of low-load blood flow restriction training on knee ... The overall results indicate that LL-BFRT significantly improves pain, muscle strength of the quadriceps, and 30STS performance compared to conventional ...

5. bmjopen.bmj.com bmjopen.bmj.com/content/15/3/e092689

The impact of blood flow restriction training combined with ... Although LL-BFRT has been shown to improve pain, muscle strength and functional performance in patients with knee joint disease,30 the impact of this therapy on ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04554212?term=NCT04554212&rank=1

Blood Flow Restriction Training After Patellar INStability This research study is designed to allow health care professionals and researchers to answer many questions about whether a new type of physical therapy ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666061X24001652

Blood Flow Restriction Training: A Tool to Enhance ... Blood flow restriction training (BFRT) is a tool utilized in rehabilitation and injury prevention to improve muscle strength and size.

8. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2025.1603568/full

Effects of blood flow restriction combined with high-load ... The findings suggest that HL-BFRT produced greater improvements in strength, speed, power, and endurance performance compared to HL-RT alone (SMD = 0.45–0.90), ...