Anterior Cruciate Ligament (ACL) Tear, Physical Therapy
Conditions
Brief summary
The purpose of the study is to determine how two different blood flow restriction training programs used in conjunction with standard rehabilitation affect leg strength. By doing this study, the investigator hopes to learn if one program improves strength and function more than the other. The investigator also hope to learn how the training affects the properties of muscle in participants who will or have had anterior cruciate ligament (ACL) reconstruction. These results will help define how the training programs are working. There will be no charge to the participant for their physical therapy visits as long as they are part of the study The initial visit and follow up assessment at the end of the training will each take up to 6 hours (2 hours for MRI, 2 muscle biopsy, 2 for muscle strength, movement mechanics and questionaires). The physical therapy visits will range from 60-120 minutes depending on the participant's stage of recovery and the activities to engage in. Training sessions will be held 3 days a week for approximately 4 weeks before surgery and up to 24 weeks after surgery. There will be a total of 4 additional study visits over a 7 month period. The first visit will be used to capture baseline conditions of their knee and thigh muscles (muscle biopsy, MRI, strength). The second visit will occur right before surgery to assess changes during prehabilitation (strength and walking mechanics). The third visit will occur 4-5 months after surgery and will be a complete reevaluation of their thigh muscle and knee function (muscle biopsy, MRI, strength, gait). The last visit will occur 6-7 months after surgery and will involve an assessment of their thigh muscle strength, walking, and jumping form. The muscle biopsy and magnetic resonance imaging portion of the study will occur in the outpatient unit of the Center for Clinical and Translational Science at the UK Medical Center and the MRI center located on the medical center campus. The muscle biopsy will take an additional 15 minutes and the MRI up to two hours (1 hour per leg). It can take up to 4 hours total to complete both procedures. The investigator will accommodate participant preference for scheduling.
Detailed description
The following procedures may be performed. Training sessions: Participants will be randomly assigned one of two groups. Assignments to which group are determined by random assignment based upon participant's number. One group will receive standard of care and the other will receive standard of care plus blood flow restriction training. The air bands will then be placed on the participant's thighs and they will be doing a standardized exercise program that will vary depending on the stage of rehabilitation they are in and as determined by the study personnel. Participants will also complete a standardized course of physical therapy. Activities in physical therapy may include ice over the knee, range of motion exercises to maintain hip strength and gait training exercises as needed and as the participant's impairments dictate. The investigator will also provide an educational program at regular intervals on the injury and recovery. Quadriceps strength: Participants will sit in a seated position and a stabilizing strap will be placed around the thigh. A second strap will be placed around the bottom of their lower leg and attached to the isokinetic dynamometer (a muscle strength testing device) which will control movements and apply force at several different speeds and in a isometric mode. Motion Analysis: Motion analysis will provide a means for evaluating motion of the participant's hip, knee and ankle joints during walking and jogging on the treadmill. Participants will have reflective markers placed on certain landmarks of their legs and lower back to allow the motion analysis system to record their trunk, hip, knee, and ankle movements. Markers will be applied with sticky tape to the skin and if necessary, athletic tape to limit marker movement during activities. A stationary trial will be collected to help the researcher identify anatomical landmarks. Motion data will be collected for 10 seconds every minute. Participants will perform a series of jumps on both legs and on a single leg. In addition participants will be asked to go up and down step. Treadmill Activity: Participants may walk on the treadmill as long as necessary to feel comfortable with it. Once ready, participants will walk at a self-selected warm up pace for 5 minutes. The investigator will then gradually increase the speed 1.5 m/s for 2 minutes each. The speed of the treadmill will then be increased gradually to a self-selected comfortable jogging\\running pace for 2 minutes. Participants may request to stop at any time. Muscle Biopsy: A small piece of muscle tissue will be removed from both of thighs. The muscle tissue will be taken from the outside of your thigh and will be taken about one hand width above your knee. A 1 inch by 1 inch portion of hair will possibly need to be shaved if necessary. The area of thigh will be numbed and a small ¼ inch incision will be made in the skin. A needle will then be briefly (lasting just a couple of seconds) inserted into the muscle to remove a .005 ounce piece of muscle (about the size of a pencil eraser). The incision will be pulled closed with a band-aid after the site is cleaned with an alcohol preparation and the participant's leg will be wrapped snugly with an elastic bandage. The procedure will last approximately 15 minutes. The tissue samples will be used in the analysis process. In addition, standard venipuncture methods will be used to collect one 7.5 mL tube of blood to be used for analysis. Magnetic Resonance Imaging & Spectroscopy Center: Participants will be asked to complete a medical screening questionnaire that will ask specific questions about their health and medical history. This information will be used to determine eligibility to participate in the study. At this time, the procedures and risks involved in participating in the research study will be explained to the individual. Participants will also fill out a questionnaire asking whether they have any metal in their body as well as any other medical conditions that may need to be considered before they enter the MRI scanner. The metal screening questionnaire will be reviewed by the individual operating the scanner and if any risks are identified, the participant may not be able to participate. Participants will be taken to the MRI scanner by the experimenter. Participants will be asked to remove all jewelry, body piercings, hair accessories, belts, wallets, credit cards, and loose change and leave these items with the experimenter. Participants will then be instructed about specific MRI procedures. The magnetic resonance scanning will take approximately 60 minutes per leg. Participants will be asked to lie still during the scanning.
Interventions
OTHERArm A - blood flow restriction training
Group receive standard of care plus blood flow restriction training
OTHERArm B - standard of care
Group will receive standard of care plus a sham version of blood flow restriction training
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Brian W. Noehren
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Participants, outcomes assessors, and the PI will be blinded as to the participant's group assignment.
Intervention model description
Parallel assignment
Eligibility
Sex/Gender
ALL
Age
15 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* ACL tear and no previous ACL reconstruction on either the involved or other limb
Exclusion criteria
* Previous surgeries or conditions that might affect gait * Any current condition other than ACL or meniscus injury which might affect gait * Unable to provided informed consent * Diabetic or have uncontrolled hypertension * Have recent inflammation, bleeding disorders, active bleeding or infection within the lower limbs. * Allergic to Betadine or Xylocaine HCL. * Taking warfarin/Coumadin, clopidogrel/Plavix, Rivaroxaban/Xarelto, Dabigatran/Pradaxa that may cause excess bleeding. * Any implanted medical device * A history of deep vein thrombosis, have a family history of deep vein thrombosis, or varicose veins * Spinal fusion * Inability able to attend regular physical therapy or study visits * Injury occurring more than ten weeks prior to study enrollment * Not skeletally mature (growth plates not closed)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure Change in Rate of Torque Development | Baseline and post-surgery (up to 5 months) | Isokinetic Dynamometer will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
| Measure Change in Isometric Peak Torque Quadriceps Strength | Baseline, and post-surgery (up to 5 months) | Assessed with a Biodex Multi-Joint System 4 Isokinetic Dynamometer. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
| Measure Change in Isokinetic Peak Torque Quadriceps Strength | Baseline and post-surgery (up to 5 months) | Assessed with a Biodex Multi-Joint System 4 Isokinetic Dynamometer. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure Change in Knee Biomechanics - Peak Knee Flexion | Baseline and post-surgery (up to 5 months) | 3D Motion Capture will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
| Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM) | Baseline and post-surgery (up to 5 months) | 3D Motion Capture will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
| Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time | Baseline, Post-surgery (up to 5 months) | MRI will be used. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
| Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA) | Baseline, Post-surgery (up to 5 months) | MRI will be used. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Measure the Change in Muscle Physiology After Using BFRT for Treatment in Patients Who Will Have an ACL Reconstruction. | Before surgery, 4 months after surgery | Muscle biopsy, which may include immunohistochemistry, histochemistry, protein expression, gene expression, or single fiber morphology may be measured. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Department of Orthopaedic Surgery & Sports Medicine at the University of Kentucky and were scheduled to undergo surgical reconstruction by one of three orthopedic surgeons.
Pre-assignment details
647 participants were assessed for eligibility. Of those, 592 participants were excluded due to not meeting inclusion criteria or declining to participate. 55 participants were randomized of which 26 received the allocated intervention (BFRT) and 26 received the SHAM intervention. 3 participants withdrew after being randomized but before receiving the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Arm A - Blood Flow Restriction Training Group will use blood flow restriction training and standard of care
Arm A - blood flow restriction training: Group receive standard of care plus blood flow restriction training | 26 |
| Arm B - Standard of Care Plus Sham Group will receive standard of care plus a sham version of blood flow restriction training
Arm B - standard of care: Group will receive standard of care plus a sham version of blood flow restriction training | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Arm A - Blood Flow Restriction Training | Arm B - Standard of Care Plus Sham | Total |
|---|---|---|---|
| Age, Continuous | 20.8 years STANDARD_DEVIATION 6 | 21.2 years STANDARD_DEVIATION 5.3 | 21.0 years STANDARD_DEVIATION 5.7 |
| Body Mass Index | 25.3 kg/m2 STANDARD_DEVIATION 4.2 | 25.7 kg/m2 STANDARD_DEVIATION 4.4 | 25.4 kg/m2 STANDARD_DEVIATION 4.5 |
| Graft Type Hamstring | 1 Participants | 2 Participants | 3 Participants |
| Graft Type Patellar | 24 Participants | 24 Participants | 48 Participants |
| Graft Type Unknown (lost to follow up before surgery) | 1 Participants | 0 Participants | 1 Participants |
| Meniscal Injury Both | 16 Participants | 14 Participants | 30 Participants |
| Meniscal Injury Lateral | 1 Participants | 4 Participants | 5 Participants |
| Meniscal Injury Medial | 7 Participants | 6 Participants | 13 Participants |
| Meniscal Injury None | 1 Participants | 2 Participants | 3 Participants |
| Meniscal Injury Unknown (lost to follow up before surgery) | 1 Participants | 0 Participants | 1 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 26 participants | 26 participants | 52 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 15 Participants | 15 Participants | 30 Participants |
| Time since injury | 20.2 Days STANDARD_DEVIATION 16.5 | 24.3 Days STANDARD_DEVIATION 16.7 | 22.3 Days STANDARD_DEVIATION 16.9 |
| Weight Bearing Status After Surgery Non-weight Bearing | 2 Participants | 1 Participants | 3 Participants |
| Weight Bearing Status After Surgery Unknown (lost to follow up before surgery) | 1 Participants | 0 Participants | 1 Participants |
| Weight Bearing Status After Surgery Weight Bearing as Tolerated | 23 Participants | 25 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 25 |
| other Total, other adverse events | 0 / 23 | 0 / 25 |
| serious Total, serious adverse events | 1 / 23 | 0 / 25 |
Outcome results
Primary
Measure Change in Isokinetic Peak Torque Quadriceps Strength
Assessed with a Biodex Multi-Joint System 4 Isokinetic Dynamometer. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline and post-surgery (up to 5 months)
Population: 1 participant excluded from isokinetic strength measurement due to injury
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Isokinetic Peak Torque Quadriceps Strength | Baseline | 1.03 Nm/kg | Standard Deviation 0.35 |
| Arm A - Blood Flow Restriction Training | Measure Change in Isokinetic Peak Torque Quadriceps Strength | Post-surgery | 1.13 Nm/kg | Standard Deviation 0.33 |
| Arm B - Standard of Care Plus Sham | Measure Change in Isokinetic Peak Torque Quadriceps Strength | Baseline | 1.00 Nm/kg | Standard Deviation 0.41 |
| Arm B - Standard of Care Plus Sham | Measure Change in Isokinetic Peak Torque Quadriceps Strength | Post-surgery | 1.09 Nm/kg | Standard Deviation 0.38 |
Primary
Measure Change in Isometric Peak Torque Quadriceps Strength
Assessed with a Biodex Multi-Joint System 4 Isokinetic Dynamometer. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline, and post-surgery (up to 5 months)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Isometric Peak Torque Quadriceps Strength | Baseline | 2.18 Nm/Kg | Standard Deviation 0.66 |
| Arm A - Blood Flow Restriction Training | Measure Change in Isometric Peak Torque Quadriceps Strength | Post-surgery | 1.96 Nm/Kg | Standard Deviation 0.59 |
| Arm B - Standard of Care Plus Sham | Measure Change in Isometric Peak Torque Quadriceps Strength | Baseline | 2.06 Nm/Kg | Standard Deviation 0.65 |
| Arm B - Standard of Care Plus Sham | Measure Change in Isometric Peak Torque Quadriceps Strength | Post-surgery | 1.95 Nm/Kg | Standard Deviation 0.57 |
Primary
Measure Change in Rate of Torque Development
Isokinetic Dynamometer will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline and post-surgery (up to 5 months)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Rate of Torque Development | Baseline | 7.10 Nm/kg/s | Standard Deviation 3.46 |
| Arm A - Blood Flow Restriction Training | Measure Change in Rate of Torque Development | Post-surgery | 5.51 Nm/kg/s | Standard Deviation 2.79 |
| Arm B - Standard of Care Plus Sham | Measure Change in Rate of Torque Development | Baseline | 6.35 Nm/kg/s | Standard Deviation 3.14 |
| Arm B - Standard of Care Plus Sham | Measure Change in Rate of Torque Development | Post-surgery | 4.68 Nm/kg/s | Standard Deviation 2.37 |
Secondary
Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM)
3D Motion Capture will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline and post-surgery (up to 5 months)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM) | Baseline | 0.16 (Nm/(kg*m) | Standard Deviation 0.11 |
| Arm A - Blood Flow Restriction Training | Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM) | Post-surgery | 0.16 (Nm/(kg*m) | Standard Deviation 0.16 |
| Arm B - Standard of Care Plus Sham | Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM) | Baseline | 0.19 (Nm/(kg*m) | Standard Deviation 0.12 |
| Arm B - Standard of Care Plus Sham | Measure Change in Knee Biomechanics - Knee Extensor Moment (KEM) | Post-surgery | 0.13 (Nm/(kg*m) | Standard Deviation 0.14 |
Secondary
Measure Change in Knee Biomechanics - Peak Knee Flexion
3D Motion Capture will be used. The primary analysis may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline and post-surgery (up to 5 months)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Knee Biomechanics - Peak Knee Flexion | Baseline | 21.51 degrees | Standard Deviation 4.66 |
| Arm A - Blood Flow Restriction Training | Measure Change in Knee Biomechanics - Peak Knee Flexion | Post-surgery | 16.87 degrees | Standard Deviation 8.05 |
| Arm B - Standard of Care Plus Sham | Measure Change in Knee Biomechanics - Peak Knee Flexion | Baseline | 22.50 degrees | Standard Deviation 4.42 |
| Arm B - Standard of Care Plus Sham | Measure Change in Knee Biomechanics - Peak Knee Flexion | Post-surgery | 16.63 degrees | Standard Deviation 4.76 |
Secondary
Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA)
MRI will be used. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline, Post-surgery (up to 5 months)
Population: Participants included in MRI analysis for this measure
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA) | Baseline | 6238.7 mm2 | Standard Deviation 1783 |
| Arm A - Blood Flow Restriction Training | Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA) | Post-surgery | 6626.0 mm2 | Standard Deviation 2484.6 |
| Arm B - Standard of Care Plus Sham | Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA) | Baseline | 6290.9 mm2 | Standard Deviation 1942.5 |
| Arm B - Standard of Care Plus Sham | Measure Change in Quadriceps Muscle Morphology - Physiological Cross-sectional Area (PCSA) | Post-surgery | 6386.6 mm2 | Standard Deviation 1862.2 |
Secondary
Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time
MRI will be used. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Baseline, Post-surgery (up to 5 months)
Population: Participants included in MRI analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A - Blood Flow Restriction Training | Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time | Baseline | 0.029 milliseconds | Standard Deviation 0.003 |
| Arm A - Blood Flow Restriction Training | Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time | Post-surgery | 0.030 milliseconds | Standard Deviation 0.002 |
| Arm B - Standard of Care Plus Sham | Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time | Baseline | 0.031 milliseconds | Standard Deviation 0.004 |
| Arm B - Standard of Care Plus Sham | Measure Change in Quadriceps Muscle Morphology - T1Rho Relaxation Time | Post-surgery | 0.029 milliseconds | Standard Deviation 0.002 |
Other Pre-specified
Measure the Change in Muscle Physiology After Using BFRT for Treatment in Patients Who Will Have an ACL Reconstruction.
Muscle biopsy, which may include immunohistochemistry, histochemistry, protein expression, gene expression, or single fiber morphology may be measured. Analyses may include the comparison of these observations over multiple time points, with a particular interest in whether there are between-group or within-patient differences.
Time frame: Before surgery, 4 months after surgery