Use of Blood Flow Restriction + Progressive Resistance Functional Training to Improve Functional Outcomes After Anterior Cruciate Ligament Reconstruction
Phase: NA
Conditions: Anterior Cruciate Ligament Injuries
Sponsor: University of Arkansas

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 1 of 21 
 
University of Arkansas for Medical Sciences (UAMS) Clinical Protocol 
 
Study Title:  
Use of Blood Flow Restriction + Standard of Care 
Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
 
Principal Investigator: 
Arny A. Ferrando, PhD, Professor 
Center for Translational Research in Aging & Longevity 
University of Arkansas for Medical Sciences 
4301 West Markham Street, Slot 806 
Little Rock, AR 72205 
Phone: 501-526-5711 
Email: aferrando@uams.edu 
 
Sub-Investigators:  
Lawrence O’Malley, M.D. 
 
 
 
 
Breanna Brumley, P.A. 
 
Christopher Oholendt, OTR/L, MHSA 
 
 
 
 
David D. Church, Ph.D. 
 
 
 
 
Katie R. Hirsch, Ph.D. 
 
 
 
 
Robin M. Smith, Ph.D. 
University of Arkansas for Medical Sciences 
4301 West Markham Street 
Little Rock, AR 72205 
 
 
 
 
 
 
Study location: 
 
UAMS Reynolds Institute on Aging 
 
 
 
 
629 Jack Stephens Drive 
 
 
 
 
Little Rock, AR 72205 
 
Funding Support:  
UAMS Dept. of Geriatrics 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 2 of 21 
 
Table of Contents 
List of Abbreviations ................................................................................................................. 4 
1.0 Protocol Summary ................................................................................................................. 5 
2.0 Background ............................................................................................................................ 5 
2.1 Significance ...................................................................................................................... 6 
3.0 Benefits and Specific Aim .................................................................................................... 7 
4.0 Study Population .................................................................................................................... 8 
4.1 Inclusion Criteria ............................................................................................................. 8 
4.2 Exclusion Criteria ............................................................................................................ 8 
4.3 Subject Recruitment ....................................................................................................... 9 
4.4 Subject Compensation................................................................................................... 9 
5.0 Study Visits ............................................................................................................................. 9 
6.0 Blinding .................................................................................................................................. 11 
7.0 Randomization ..................................................................................................................... 11 
8.0 Intervention Description ...................................................................................................... 12 
9.0 Outcome Measures ............................................................................................................. 12 
9.1 10-meter Walking Speed .............................................................................................. 12 
9.2 Maximum Voluntary Contraction .............................................................................. 13 
9.3 Y-Balance Test ............................................................................................................... 13 
9.4 Stair Ascent/Descent .................................................................................................... 13 
9.5 Dual Energy-Xray Absorptiometry ............................................................................ 14 
9.6 InBody Bioelectrical Impedance Analysis .............................................................. 14 
9.7 Clinical Data Collection ............................................................................................... 14 
9.7.1 Quantitative Pain Scores ................................................................................. 1514 
9.7.2 Fear and Avoidance Beliefs Questionnaire .................................................... 15 
9.7.3 Range of Motion ..................................................................................................... 15 
9.7.4 Rehabilitation Volume: study staff will obtain total exercise volume, duration, 
and load from physical therapist’s notes in Epic. .............................................................. 15 
9.8 Order of Outcome Tests .............................................................................................. 15 
10.0 Data Analysis, Use and Handling ................................................................................... 15 
10.1 Statistical Analysis/Power Calculations ............................................................... 15 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 3 of 21 
 
10.2 Dissemination of Data ................................................................................................ 16 
10.3 Data Handling and Recordkeeping......................................................................... 16 
10.4 Data Access .................................................................................................................. 16 
11.0 Risks and Benefits ............................................................................................................ 17 
11.1 ........................................................................................................................................... 17 
Physical, Functional, Range of Motion Testing ........................................................... 17 
11.2 Blood Flow Restriction device ................................................................................ 17 
11.3 DEXA Scan ................................................................................................................ 1817 
11.4 InBody Bioelectrical Impedance scan ................................................................... 18 
11.5 Confidentiality .............................................................................................................. 18 
11.6 Data Safety Monitoring Plan..................................................................................... 18 
12.0 Ethical Considerations ...................................................................................................... 18 
13.0 
References ................................................................................................................... 19 
 
 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 4 of 21 
 
List of Abbreviations 
 
ACL 
Anterior cruciate ligament 
BFR 
Blood Flow Restriction 
CRF 
Case Report Form 
DEXA 
Dual-energy X-ray Absorptiometry 
EMR 
Electronic medical record 
FDA 
Food and Drug Administration 
IRB 
Institutional Review Board 
MVC 
Maximal voluntary contraction (of the quad muscles) 
NIH 
National Institutes of Health  
PBFR 
Personalized Blood Flow Restriction 
PT 
Physical Therapist 
RIOA 
Reynolds Institute on Aging 
ROM 
Range of Motion (of the knee joint) 
UAMS 
University of Arkansas for Medical Sciences 
UPIRTSO 
Unexpected problem involving risks to subjects or others 
 
 
Study Schema 
 
Surgeon collaborators or their designees screen their orthopedic clinic for eligible 
subjects and send referrals to study staff via UAMS email. 
 
Study staff contact referrals via phone or email to discuss consent process. 
 
Visit 1: Subjects come to RIOA for informed consent process prior to surgery. 
Randomization (1:1) occurs. 
 
Visit 2: Approx. 7-10 days prior to surgery, subjects come to RIOA for baseline testing. 
 
***Subjects undergo scheduled knee surgery at UAMS*** 
 
***Prescribed physical therapy begins with or without BFR per randomization at UAMS 
Colonel Glenn facility*** 
 
Visit 3: Subjects come to RIOA for post-operative testing approx. 8 weeks postop. 
 
***Prescribed physical therapy continues with/without BFR per randomization*** 
 
Visit 4: Approx. 12 weeks postop, subjects come to RIOA for mid-point testing. 
 
Visit 5: Approx. 16 weeks postop, subjects come to RIOA for end-point testing. 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 5 of 21 
 
 
Study Calendar 
 
 
1.0 Protocol Summary 
 
This will be a randomized pilot study to determine the effectiveness of Personalized 
Blood Flow Restriction (PBFR) technique in conjunction with prescribed physical 
therapy (PT) in a cohort of anterior cruciate ligament (ACL) reconstruction subjects. 
Both groups of subjects will undergo unilateral ACL reconstruction at University of 
Arkansas for Medical Sciences (UAMS), followed by prescribed PT at the UAMS 
Orthopedic Clinic at Colonel Glenn. 
Up to 25 subjects will be enrolled. Half are randomized to the BFR group with the other 
will perform PT without BFR. 
Data collection will occur at four approximate occasions: pre-surgery, 8-weeks postop, 
12-weeks postop, and 16-weeks postop. 
 
2.0 Background 
 
Anterior cruciate ligament tears are a costly injury; rehabilitation time is extensive and 
return to pre-injury activity is often limited. Between 1990 and 2010 the overall age- and 
sex-adjusted annual incidence of Anterior Cruciate Ligament (ACL) tears in the U.S. 
was 68.6 per 100,000 person-years (1).  A 2014 study reported 81 ruptures per 100,000 
people (2).  The incidence of ACL injuries among United States service members is 10 
times the reported rate for the U.S. population as a whole (3). More than 50% of service 
members have activity limitations or are unable to return to duty following surgery. The 
Procedure 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Informed consent 
X 
 
 
 
 
10-meter walk test 
 
X 
X 
X 
X 
bilateral MVC 
 
X 
X 
X 
X 
DEXA scan 
 
X 
X 
X 
X 
In Body scan 
 
X 
X 
X 
X 
Stair ascent 
 
 
X 
X 
X 
Stair descent 
 
 
 
X 
X 
Y-balance test 
 
 
X 
X 
X 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 6 of 21 
 
possibility exists that an anterior cruciate ligament tear, even when reconstructed, can 
lead to permanent military activity limitations and Medical Evaluation Board (MEB) (4).   
 
Approximately 80% of ACL reconstruction surgeries are accompanied by meniscal tear 
and repair. Meniscal repairs require load restrictions for several weeks immediately 
following surgery (5). During this time, muscle atrophy and loss of strength occurs. In 
order to mitigate muscle atrophy and loss of strength, we propose using Personalized 
Blood Flow Restriction (PBFR). PBFR will adjust to the participant’s current blood flow 
in order to keep a constant level of blood flow restriction, thus customizing blood flow 
restriction for each person. Though the device technology readily available, many 
studies have utilized a consistent cuff pressure rather than a consistent cuff flow 
restriction.  
 
The use of BFR for ACL rehabilitation is gathering support. LaPrade (6) observed the 
greatest benefit of BFR for individuals who are non-weight-bearing for six to eight weeks 
and who may have more postoperative restrictions. Quadriceps girth has been 
preserved to contralateral standards with BFR following the non-weight-bearing period. 
There have been only a few studies published on BFR and ACL. Ohta, et al (7) used 
low-load resistance muscular training with moderate BFR after ACL reconstruction.  
However, their study used a standard occlusion pressure, additional home training, and 
the involvement of meniscal tear/repair was uncertain. Bowman, et al (8) found that 
BFR training strengthens muscle groups proximal, distal, and contralateral to cuff 
placement following ACL repair. However, their measures were not elegant and the 
study was not blinded. Only one study (9) evaluated physical functional outcomes, 
though they were self-reported. Thus, there is a need to evaluate the use of BFR after 
ACL surgery in a randomized, clinical trial.  
2.1 Significance 
Participants will attend their usual physical therapy visits and be randomized to receive 
PBFR or standardized rehabilitation. This use of a current and standardized clinical 
program and experienced physical therapists determines both suitability and clinical 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 7 of 21 
 
translation.  We propose to evaluate physical functional outcomes with a blinded tester 
and quantifiable measures that are standards in our hands. The goal of this pilot project 
is to demonstrate the potential to steepen the healing curve after ACL repair. The 
improved healing time will translate to an earlier return to weight bearing and the 
resumption of normal activities or duty. In addition to pre-test and post-test, we will 
incorporate two additional testing points over the length of the physical therapy 
sessions. This testing schedule will identify progress in functional outcome recovery 
over the course of rehabilitation. If successful, this rehabilitative modality may allow 
rehabilitation economics to be truncated and an earlier return to function. This pilot 
study will provide data, process refinement, and methods confirmation in preparation for 
a larger project submission.  
 
3.0 Benefits and Specific Aim 
 
There is a growing body of evidence demonstrating that the combination of blood flow 
restriction (BFR) with low intensity resistance exercise can induce similar gains in 
muscular strength and hypertrophic adaptations as moderate or high intensity 
resistance training (10). BFR is an attractive modality for patients after ACL 
reconstruction due to its efficacy with low intensity resistance exercise. The attractive 
aspect of PRFT with BFR is that strength and functional improvements may be 
garnered over a shorter period of time and more importantly, with lower training loads. 
The lower training load is particularly applicable to post-ACL patients with 
accompanying pain and diminished function and weight bearing. The ability to improve 
strength and function with a reduced total rehabilitation is an attractive financial and 
pragmatic solution in this patient population. Therefore, we propose a pilot project to 
determine the effects of adding PBFR to the standard of care on strength and functional 
outcomes after ACL reconstruction. We will compare the benefits of three times weekly 
standard of care including PBFR training versus standard of care rehabilitation 
throughout 16 weeks post ACL reconstruction. 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 8 of 21 
 
Specific Aim: To determine the effects of PT + PBFR after elective ACL surgery on 
muscle mass, strength, and function. 
 
4.0 Study Population 
 
Up to 25 subjects of any gender or ethnicity will be enrolled with a target of n=20 for 
study completion. 
 
4.1 Inclusion Criteria 
1. Men and women, ages 18-34 years. 
2. Scheduled to undergo elective ACL surgery at UAMS. 
3. Capable of providing informed consent. 
4. Willing to exercise with BFR. 
5. COVID-19 negative or asymptomatic. 
 
4.2 Exclusion Criteria 
1. Any surgical indication other than ACL repair. 
2. Body mass index >40. 
3. Pregnant female.  
4. Neurological, musculoskeletal, or other disorder that would preclude them from 
completing the exercise training intervention and all performance tests. 
5. Hypertension as evidenced by systolic BP >150 at rest OR diastolic BP >85 at 
rest. 
6. Heart failure as evidenced by use of prescription diuretics. 
7. History of atrial fibrillation. 
8. Oxygen saturation <95% on room air at rest. 
9. Any other medical condition that would interfere with testing or increase one's 
risk of complications during exercise. 
10. Currently receiving androgen (e.g., testosterone) or anabolic (e.g., GH, IGF-I) 
therapy. 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 9 of 21 
 
11. Compromised vascular circulation in the legs (e.g. peripheral vascular disease). 
12. History of deep vein thrombosis. 
13. Varicose veins in the legs. 
14. Known Sickle cell disease or trait. 
15. Unwilling to avoid using protein or amino-acid supplements during participation. 
16. Unwilling to avoid using BFR during prescribed post-operative physical therapy. 
 
 
4.3 Subject Recruitment 
Subjects will be recruited by the surgeon or their designee. Referrals will be sent to 
study staff via email. Study staff will contact referrals using their preferred method of 
communication (as per Epic) and present the study overview to them. Interested 
subjects will then be scheduled for Visit 1 where the informed consent process will take 
place in the Reynolds Institute on Aging. 
 
4.4 Subject Compensation 
Subjects will be compensated for participation as shown in the table below. They will be 
given a Visa ® gift card for visit 1, and be handed a UAMS check for the sum of their 
participation$50 at the completion of each other study visit when their participation ends 
(unless they request more frequent compensation). Parking passes will be provided to 
all subjects for all RIOA visits at no cost to subjects. 
 
Visit 1 
$25 
Visit 2 
$50 
Visit 3 
$50 
Visit 4 
$50 
Visit 5 
$50 
 
 
5.0 Study Visits 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 10 of 21 
 
Subjects will be required to wear a mask. If they do not have one, a mask will be 
provided to them by the study staff.  
 
Visit 1: This visit will take place at the UAMS RIOA prior to surgery. At this visit, 
informed consent discussion will be held. Study staff will use appropriate PPE. This visit 
is expected to take less thanabout one hour. If a subject consents, their vital signs will 
be measured (blood pressure, oxygen saturation) while at rest for at least 10 minutes 
for exclusion criteria. Randomization will occur. Mr. Oholendt will be notified via email as 
to which group each enrolled subject has been randomized. He will then communicate 
this to the relevant physical therapists at the Col. Glenn facility. 
 
Visit 2: This fasted visit will occur approximately 7-10 days before surgery. Subjects will 
be asked to fast for 8 hours, avoid caffeine and alcohol for 12 hours, and avoid 
strenuous exercise for 24 hours prior to this visit. Subjects will undergo body 
composition testing (DEXA, InBody). After a 5 minute warm up 
(stretching/walking/cycling as tolerated),, strength testing of each leg, and 10-meter 
walking speed test will commence. This visit is expected to take about 1 hour. 
 
Visit 3: This visit will take place at the UAMS RIOA approximately 8 weeks after surgery. 
Subjects will be asked to fast for 8 hours, avoid caffeine and alcohol for 12 hours, and 
avoid strenuous exercise for 24 hours prior to this visit. At this visit, a 5-minute warm up, 
physical, functional, and body composition testing (DEXA, InBody) will take place (see 
Study Calendar). Future study visits will be scheduled. This visit is expected to take 
about 1 hour. 
 
Visit 4: This visit will take place at the UAMS RIOA approximately 12 weeks after 
surgery. Subjects will be asked to fast for 8 hours, avoid caffeine and alcohol for 12 
hours, and avoid strenuous exercise for 24 hours prior to this visit. At this visit, a 5-
minute warm up, physical, functional, and body composition testing (DEXA, InBody) will 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 11 of 21 
 
take place (see Study Calendar). Future study visits will be scheduled. This visit is 
expected to take about 1 hour. 
 
Visit 5: This visit will take place at the UAMS RIOA approximately 16 weeks after 
surgery. Subjects will be asked to fast for 8 hours, avoid caffeine and alcohol for 12 
hours, and avoid strenuous exercise for 24 hours prior to this visit. At this visit, a 5-
minute warm up, physical, functional, and body composition testing (DEXA, InBody) will 
take place (see Study Calendar). Future study visits will be scheduled. This visit is 
expected to take about 1 hour. 
 
As part of PT, subject’s level of pain will be ascertained using a 0-10 point scale at the 
onset of their PT visits. They will also be asked to complete the Fear-Avoidance Beliefs 
Questionnaire at some visits. The ROM of their surgical knee will be measured at 
certain times. In addition, progression towards UAMS’ ‘Return to Sport’ measurements 
are performed and documented. Some of these data elements will be retrieved from the 
therapist’s notes in Epic by study staff. 
 
6.0 Blinding 
 
The study is a single-blind, randomized, controlled trial (RCT). While participants cannot 
be blinded since BFR is the intervention being evaluated, key investigators and 
outcomes assessors will be blinded to treatment assignment, making this a single-blind 
RCT from the investigators’ perspective. 
 
7.0 Randomization 
 
Subjects will be randomized 1:1 at the conclusion of Visit 1 using a randomly generated 
list of group designations that corresponds to subject ID. 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 12 of 21 
 
8.0 Intervention Description 
 
All subjects will have the standard physical therapy visits conducted by the PTs at the 
Colonel Glenn facility.  Participants will undergo standard physical therapy sessions at 
UAMS’ Colonel Glenn facility either with or without the use of the BFR apparatus. 
Subjects will progress through the goals set by their therapist as their condition permits. 
Physical Therapists will be the same (Colonel Glenn therapists) for both intervention 
and standard of care groups to standardize treatment. The physical therapists 
participating in the study have all demonstrated proficiency in the BFR approach. 
Briefly, the BFR apparatus consists of an electronically controlled pneumatic 
tourniquet(s) that is placed (in this study) on the upper thigh(s) and inflated during 
exercise. The control mechanism continuously adjusts the air pressure to maintain the 
operator-chosen percentage of arterial occlusion (e.g. 75%) as determined by the blood 
pressure of that limb for a determined amount of time (e.g. for the duration of 4 sets of 
30:15:15:15 3 sets of 8 repetitions of knee flexion/extension). The tourniquet is deflated 
at specific intervals. The BFR apparatus is used primarily in the early stages of 
rehabilitation with the goal of increasing the strength and endurance of that limb at a 
faster rate than performing the exercises without BFR. 
 
9.0 Outcome Measures 
 
9.1 10-meter Walking Speed 
This test is performed in a quiet, well-lit hallway. Subjects are instructed to walk as 
quickly as they can without running through a 20-meter course. The middle 10 meter 
distance is timed using stationary timer devices. Subjects will be accompanied by study 
staff for safety purposes but will not help the subject unless required. 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 13 of 21 
 
9.2 Maximum Voluntary Contraction 
Using the Cybex Dynamometer, isometric testing will be used to measure maximal 
muscle strength defined as the highest peak torque (Nm) obtained during knee 
extension of each leg separately. Subjects will be securely seated in the machine to 
ensure safety and stability for the test. Adjustments will be made to align the knee and 
ankle with the testing equipment. After a practice set to familiarize participants with the 
equipment, subjects will have three attempts of 5 seconds each separated by two 
minutes of rest between attempts. The highest peak torque reading will be 
recorded.  Subjects will be measured first on the surgical right leg and next on the non-
surgicalleft leg. If a subject has recently (~1 week) performed this same measurement 
as part of their prescribed physical therapy, study staff will ask for the results. If results 
are provided, duplicate testing will not be performed. 
 
9.3 Y-Balance Test 
This test is used to assess lower body strength and balance. Study staff will 
demonstrate the test positions. With study staff within reach of subject, subject will have 
a practice trial and then will have 3 scored attempts.  The greatest distance for each leg 
will be recorded for each of three positions (anterior, Posterior lateral, and medial 
lateralattempt to reach the most distance in each of the 3 positions. The maximum 
distance reached is recorded in cm. Subjects will perform this test with each leg. 
 
9.4 Stair Ascent/Descent 
This test is a physical performance measure that assesses the time it takes the subject 
to ascend and/or descend a flight of twelve, 18-cm high steps with a depth of 28 cm.  
Participants will be asked to complete the test as quickly as they feel safe and 
comfortable. Handrails are allowed if required, but subjects are encouraged to use just 
their legs for stair negotiation. Time to negotiate the stairs is measured to the nearest 
one hundredth of a second with by stationary timing devices a stopwatch.  A partial 
practice trial is completed to gauge subject capability and ensure safety monitoring, 
then the mean of two subsequent trials is used for analysis.  Assistive devices are 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 14 of 21 
 
allowed only if the participant is unsafe or could not complete the test without a cane or 
walker.  The use of assistive devices, as well as use of the handrail, is recorded.   
 
9.5 Dual Energy-Xray Absorptiometry 
This test will be used to measure body composition (fat mass, lean mass, and percent 
body fat). Subjects will be asked to remove all metal, thick clothing, and heavy plastic 
which could interfere with the DEXA scans. The subject’s ID, age, ethnicity, height and 
weight will be entered into the computer prior to the scanning. The subject will be asked 
to lie down on the DEXA table in the supine position. The participant will be centered on 
the table within the scanning area. The subject’s shoulders and hips will be centered, 
and the hands will be placed by the side of the legs in a prone position. Subjects will be 
instructed to remain still for the duration of the full-body scan. A trained DEXA 
technician will perform and analyze all scans. Subjects will be asked to fast for 8 hours, 
avoid caffeine and alcohol for 12 hours, and avoid strenuous exercise for 24 hours prior 
to this procedure. 
 
9.6 InBody Bioelectrical Impedance Analysis 
This test will measure total body and segmental water, to be combined with the DEXA 
measures for a more accurate body composition estimates. To obtain measurements, 
subjects are asked to stand barefoot on a calibrated scale to obtain subject weight. 
Once subject height, sex, and age are entered into the device, subjects are instructed to 
hold onto two handles and remain still while an imperceptible electrical current runs 
between electrodes in the handles and scale. Total assessment time is <2 minutes. 
Subjects will be asked to fast for 8 hours, avoid caffeine and alcohol for 12 hours, and 
avoid strenuous exercise for 24 hours prior to this procedure. 
 
9.7 Clinical Data Collection 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 15 of 21 
 
9.7.1 Quantitative Pain Scores: study staff will obtain pain scores that were 
assessed by physical therapists by reading the visit notes written by the therapist 
in Epic. Scores will be captured up through visit 5. 
9.7.2 Fear and Avoidance Beliefs Questionnaire: study staff will obtain these 
scores that were documented by physical therapists by reading the visit notes 
written by the therapist in Epic. Scores will be captured up through visit 5. 
9.7.3 Range of Motion: study staff will obtain ROM values that were assessed 
by physical therapists by reading the visit notes written by the therapist in Epic. 
Values will be captured up through visit 5. 
9.7.4 Rehabilitation Volume: study staff will obtain total exercise volume, 
duration, and load from physical therapist’s notes in Epic.  
 
9.8 Order of Outcome Tests 
Outcome measures will be performed in the following order for every visit: 
DXA scan 
InBody composition 
MVC 
10-meter walking speed 
Stair ascent/descent 
Y-balance 
 
10.0 Data Analysis, Use and Handling  
 
10.1 Statistical Analysis/Power Calculations 
Descriptive statistics for numeric outcome measures as well as demographic and 
clinical characteristics will be reported as means and standard deviations or medians 
and interquartile ranges, as appropriate. For each strength and functional outcomes, the 
difference between the two groups by the mid-point and final visit will be tested with 
two-sided hypotheses at a significance level of 0.05. For each parameter, an analysis of 
Formatted: Font: (Default) Arial, Bold, Font color: Auto
Formatted: Heading 2, Adjust space between Latin
and Asian text, Adjust space between Asian text and
numbers
Formatted: Font: (Default) Arial, Bold

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 16 of 21 
 
covariance (ANCOVA) model will include terms for the main model effect of intervention 
group with pretest as a covariate for each parameter. For each group comparison, 
homogeneity of variances, normality, and parallel posttest-pretest slopes will be 
assessed. In the case of non-normal distributions, data transformations will be 
evaluated and applied if appropriate. Otherwise, for any group comparison with unmet 
ANCOVA assumptions, an alternative analysis such as generalized linear mixed models 
will be pursued instead. Statistical analysis will be performed using SAS version 9.4.  
The objective of this pilot work is to obtain adequate data on which to power future 
studies and project submissions.  
 
10.2 Dissemination of Data 
Results of this study may be used for presentations, posters, or publications. The 
publications will not contain any identifiable information that could be linked to a subject. 
 
10.3 Data Handling and Recordkeeping 
Physical Therapy sessions will be documented by Physical Therapists in EPIC. Data will 
be transferred from EPIC to the UAMS data warehouse and then imported into REDCap 
so no mistakes are introduced between data collection and data analysis. Outcome 
testing data (without identifiers) will be entered into REDCap to facilitate analyses. 
These files are maintained on secure password-protected UAMS servers. 
Approximately 7 years after study completion, electronic records will be destroyed per 
UAMS disposal guidelines. At no time shall Protected Health Information be released to 
non-study personnel. 
 
10.4 Data Access 
All subjects will be assigned a unique identifying code or number.  The key to the code 
(the instrument associating the data with subject identity) will be kept on a password-
protected UAMS server.  Only study staff members will have access to the code and 
information that identifies the subject in this study. This file will be deleted approximately 
seven years after data analysis is completed. 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 17 of 21 
 
Epic medical record will be accessed by study staff to extract specific data from the PT 
notes for exercises performed, noting repetitions, sets, resistance, occlusion, pain level, 
Fear-Avoidance Beliefs questionnaire, and ROM measurements. 
 
11.0 Risks and Benefits 
 
There are no guaranteed benefits for the subjects, though there is some evidence that 
additional rehabilitation improves functional outcomes. Anticipated risks associated with 
this protocol are described in detail below. All experimental procedures will be 
performed by appropriately trained and credentialed personnel. The PI and/or study 
physician will be responsible for oversight of study procedures and evaluation of 
adverse events.  
There are no known risks of answering the questions on the Fear and Avoidance Belief 
questionnaire that the Physical Therapy department uses. 
 
11.1  
Physical, Functional, Range of Motion Testing  
The primary risks are fatigue and muscle soreness. 
  
11.2 Blood Flow Restriction device 
Possible adverse effects which may occur from performing blood flow restriction 
techniques using a pneumatic tourniquet include bruising at the site of the cuff, 
numbness, cold feeling, venous thrombus, fainting/dizziness, delayed onset muscle 
soreness, increased perceived exertion/pain/discomfort, stiffness, weakness, skin 
discoloration, exercise-induced rhabdomyolysis.  Symptoms of tourniquet paralysis are 
motor paralysis and loss of touch, pressure, and proprioceptive responses. The physical 
therapists participating in the study have all demonstrated proficiency in the BFR 
approach. 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 18 of 21 
 
11.3 DEXA Scan  
Subjects will undergo four DEXA scans for whole-body composition. The radiation 
exposure for one DEXA scan is approximately equal to ½ of the radiation from a chest 
x-ray. 
 
11.4 InBody Bioelectrical Impedance scan 
Subjects will undergo four of these scans. This machine (InBody770, BioSpace, Seoul, 
South Korea) is a widely used commercial device that is FDA approved and poses no 
risks. 
 
11.5 Confidentiality 
A potential risk to study subjects is the loss of confidentiality.  Measures to protect the 
confidentiality of study subjects will be implemented as described in the Data Handling 
and Recordkeeping section above. 
 
11.6 Data Safety Monitoring Plan 
 Study staff will ask subjects about the occurrence of adverse events during study 
visits. 
 Physical therapists will monitor for adverse events during intervention/rehab 
visits. These will be documented in their Epic notes. 
 The PI and study physician are responsible for reviewing and evaluating adverse 
events. 
 Adverse events will be recorded in the CRF and on an excel spreadsheet that is 
submitted to the IRB at required intervals. 
 UPIRTSOs will be reported to the IRB within 24 hours of their discovery. 
 
 
12.0 Ethical Considerations 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 19 of 21 
 
This study will be conducted in accordance with all applicable government regulations 
and University of Arkansas for Medical Sciences (UAMS) research policies and 
procedures.  This protocol and any amendments will be submitted and approved by the 
UAMS Institutional Review Board (IRB) to conduct the study. 
The formal consent of each subject, using the IRB-approved consent form, will be 
obtained before that subject is submitted to any study procedure.  All subjects for this 
study will be provided a consent form describing this study and providing sufficient 
information in language suitable for subjects to make an informed decision about their 
participation in this study.  The person obtaining consent will thoroughly explain each 
element of the document and outline the risks and benefits, alternate treatment(s), and 
requirements of the study.  The consent process will take place in a quiet and private 
room, and subjects may take as much time as needed to make a decision about their 
participation. Participation privacy will be maintained and questions regarding 
participation will be answered.  No coercion or undue influence will be used in the 
consent process. This consent form must be signed by the subject and the individual 
obtaining the consent.  A copy of the signed consent will be given to the participant, and 
the informed consent process will be documented in each subject’s research record. 
 
13.0 
References 
 
1. 
Hwang PS, and Willoughby DS. Mechanisms Behind Blood Flow–Restricted Training and 
its Effect Toward Muscle Growth. The Journal of Strength & Conditioning Research. 
2019;33:S167-S79. 
2. 
Humphries B, Stanton R, Scanlan A, and Duncan MJ. The prevalence and performance 
of resistance exercise training activities in an Australian population in relation to health 
authority guidelines. J Sci Med Sport. 2018;21(6):616-20. 
3. 
Schoenfeld BJ, Peterson MD, Ogborn D, Contreras B, and Sonmez GT. Effects of Low- 
vs. High-Load Resistance Training on Muscle Strength and Hypertrophy in Well-Trained 
Men. Journal of strength and conditioning research / National Strength & Conditioning 
Association. 2015;29(10):2954-63. 
4. 
Curran MT, Bedi A, Mendias CL, Wojtys EM, Kujawa MV, and Palmieri-Smith RM. Blood 
Flow Restriction Training Applied With High-Intensity Exercise Does Not Improve 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 20 of 21 
 
Quadriceps Muscle Function After Anterior Cruciate Ligament Reconstruction: A 
Randomized Controlled Trial. Am J Sports Med. 2020;48(4):825-37. 
5. 
Kilgas MA, Lytle LLM, Drum SN, and Elmer SJ. Exercise with Blood Flow Restriction to 
Improve Quadriceps Function Long After ACL Reconstruction. Int J Sports Med. 
2019;40(10):650-6. 
6. 
Kilgas MA, DenHerder AE, Lytle LLM, Williams CT, and Elmer SJ. Home-Based Exercise 
With Blood Flow Restriction to Improve Quadriceps Muscle and Physical Function After 
Total Knee Arthroplasty: A Case Report. Physical therapy. 2019;99(11):1495-500. 
7. 
Wernbom M, Apro W, Paulsen G, Nilsen TS, Blomstrand E, and Raastad T. Acute low-
load resistance exercise with and without blood flow restriction increased protein signalling 
and number of satellite cells in human skeletal muscle. European journal of applied 
physiology. 2013;113(12):2953-65. 
8. 
Singh JA, Sloan JA. Health-related quality of life in veterans with prevalent total knee 
arthroplasty and total hip arthroplasty. Rheumatology (Oxford). Dec 2008;47(12):1826-
1831. 
 
9. 
Singh JA, Lewallen DG. Predictors of activity limitation and dependence on walking aids 
after primary total hip arthroplasty. J Am Geriatr Soc. Dec 2010;58(12):2387-2393. 
 
10. 
Singh JA, Lewallen DG. Diabetes: a risk factor for poor functional outcome after total 
knee arthroplasty. PLoS One. 2013;8(11):e78991. 
 
11. 
Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical 
inactivity on major non-communicable diseases worldwide: an analysis of burden of 
disease and life expectancy. Lancet. Jul 21 2012;380(9838):219-229. 
 
12. 
Singh JA, Sloan J. Higher comorbidity, poor functional status and higher health care 
utilization in veterans with prevalent total knee arthroplasty or total hip arthroplasty. Clin 
Rheumatol. Sep 2009;28(9):1025-1033. 
 
13. 
Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and 
knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. Apr 
2007;89(4):780-785. 
 
14. 
Lavernia CJ, D'Apuzzo MR, Hernandez VH, Lee DJ, Rossi MD. Postdischarge costs in 
arthroplasty surgery. J Arthroplasty. Sep 2006;21(6 Suppl 2):144-150. 
 
15. 
Lavernia CJ, Hernandez VH, Rossi MD. Payment analysis of total hip replacement. Curr 
Opin Orthop. 2007;18(1):23-27. 
 
16. 
Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: a disease of the 
joint as an organ. Arthritis Rheum. Jun 2012;64(6):1697-1707. 
 

Use of Blood Flow Restriction + Standard of Care Physical Therapy to Improve Functional Outcomes after 
Anterior Cruciate Ligament Reconstruction 
PI: Arny A. Ferrando, Ph.D. 
Institution: UAMS 
Sponsor: UAMS 
261865 protocol v.110 03Dec16May22 
Page 21 of 21 
 
17. 
Reardon K, Galea M, Dennett X, Choong P, Byrne E. Quadriceps muscle wasting 
persists 5 months after total hip arthroplasty for osteoarthritis of the hip: a pilot study. 
Intern Med J. Jan-Feb 2001;31(1):7- 14. 
 
18. 
Rasch A, Bystrom AH, Dalen N, Martinez-Carranza N, Berg HE. Persisting muscle 
atrophy two years after replacement of the hip. The Journal of bone and joint surgery. 
May 2009;91(5):583-588. 
 
19. 
Husby VS, Helgerud J, Bjorgen S, Husby OS, Benum P, Hoff J. Early postoperative 
maximal strength training improves work efficiency 6-12 months after osteoarthritis-
induced total hip arthroplasty in patients younger than 60 years. Am J Phys Med 
Rehabil. Apr 2010;89(4):304-314. 
 
20. 
Suetta C, Magnusson SP, Rosted A, et al. Resistance training in the early postoperative 
phase reduces hospitalization and leads to muscle hypertrophy in elderly hip surgery 
patients--a controlled, randomized study. J Am Geriatr Soc. Dec 2004;52(12):2016-
2022. 
 
21. 
Skoffer B, Dalgas U, Mechlenburg I. Progressive resistance training before and after 
total hip and knee arthroplasty: a systematic review. Clinical rehabilitation. Jul 3 2014. 
 
22. 
Minns Lowe CJ, Barker KL, Dewey ME, Sackley CM. Effectiveness of physiotherapy 
exercise following hip arthroplasty for osteoarthritis: a systematic review of clinical trials. 
BMC Musculoskelet Disord. 2009;10:98.