Moderated Blood Flow Restriction After Anterior Cruciate Ligament
Phase: NA
Conditions: Anterior Cruciate Ligament Tear
Sponsor: University of Missouri-Columbia

 
 
 
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Moderated Blood Flow Restriction after Anterior 
Cruciate Ligament Reconstruction 
 
Identifiers: NCT02911909    
 
Unique Protocol ID: 2004255 
 
Date: 06-14-2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Date: 06-14-2019  
Version Number: 3.1 
Principal Investigator: James L. Cook, DVM, PhD, OTSC 
Application Number: 2004255 
Application Title: Moderated blood flow restriction after anterior cruciate ligament reconstruction 
 
 
Moderated Blood Flow Restriction after Anterior Cruciate Ligament Reconstruction  
 
Principal Investigator: James L. Cook, DVM, PhD, OTSC 
Department of Orthopaedics 
1100 Virginia Avenue, Columbia, MO 65212 
Email: CookJL@health.missouri.edu 
Phone number: (573) 884-4689 
 
   
Coordinating Site: University of Missouri, Missouri Orthopaedic Institute  
 
Funding: Department of Orthopaedic Surgery, University of Missouri  
 
Hypothesis- Patients in the moderated blood flow (Delfi) restriction group will have significantly increased 
muscle strength, thigh circumference, HGH and IGF levels, and no significant differences in knee range of 
motion, Lachman exam, KT2000, IKDC, Tegner, PROMIS surveys, VAS scores, or CK levels compared 
with standard ACL rehabilitation patients. 
 
Background: 
ACL injury is a common and potentially devastating injury. Approximately 80,000 ACL tears occur 
annually in the United States (1). 50,000 of those will go on to have ACL reconstruction surgery (2). Goals 
of reconstruction surgery and rehabilitation include: joint stability, restoration of knee function, and return 
to preinjury activities. The quadriceps is critical to dynamic joint stability, and weakness of this muscle 
group is related to poor functional outcomes. Because of this, identifying strategies to minimize quadriceps 
weakness following ACL injury and reconstruction is of great clinical interest (3). 
Moderated blood flow training, was developed in 1966 by Dr. Yoshiaki Sato of Japan. This training 
technique uses specialized pneumatic belts, placed on the upper arms or legs that moderate blood flow to 
the distal extremity leading to engorgement of blood in the arms and legs. This exercise method has been 
shown to be safe and effective in producing muscle hypertrophy at lower intensity training (4,5). Typically 
a training intensity of more than 65% of one repetition maximum (1 RM) is considered the minimum 
intensity required to achieve muscle hypertrophy and strength gains (6). However, such intensive weight 
may not be possible or safe in the postoperative patient population. With moderated blood flow training, 
substantial muscle hypertrophy can occur using a training intensity as low as 20% of 1 RM (6). Moderated 
blood flow training provides a safe, less intense, but still effective means to promote muscle hypertrophy in 
the post-operative ACL patient. We hypothesize that patients randomized to standard physical therapy with 
moderated blood flow training will demonstrate significantly increased muscle strength, muscle mass, 
HGH, IGF levels, and no significant differences in knee range of motion, Lachman exam, KT2000, VAS 
scores, and CK levels compared with standard physical therapy without moderated blood flow in post-

 
 
 
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operative ACL patients. This in turn could lead to faster, yet safer, return to functional day-to-day activities 
and sport.  
 
 
 
 
 
Objectives: To determine if there are significant differences in muscle strength, thigh circumference, knee 
range of motion, VAS, IKDC, Tegner, PROMIS surveys, HGH, IGF, CK levels, KT2000, and Lachman’s 
exam in those patients that participate in moderated blood flow postoperative ACL physical therapy vs. 
standard ACL post-operative physical therapy.  
 
Study Procedures 
a. The study will be a prospective, randomized, controlled trial between two treatment cohorts. A total 
of 50 patients will be enrolled in the study. Informed consent will be obtained in clinic or by 
phone (Patient IQ e-consent) prior to any surgical intervention, per the IRB protocol. 
Enrollees will receive a copy of the consent and HIPAA form. All patients that meet inclusion 
criteria who consent to participate in the study will then be randomly assigned to either the control 
group or moderated blood flow therapy group. Randomization will occur by autogenerated 
permutated 1:1 block randomization using electronic assignment from the orthopaedic research 
team prior to initiation of post-operative therapy. The control group will undergo standard of care, 
post-operative ACL reconstruction rehabilitation. The treatment group will also receive standard 
ACL rehabilitation combined with Delfi moderated blood flow restriction therapy. Patients will 
follow up at standard of care clinic visits and participate in the same standard of care physical 
therapy protocol for ACL reconstruction. Baseline measurements of thigh circumference, knee 
ROM, KT 2000, Lachman exam, and labs for HGH, IGF, and CK will be obtained preoperatively. 
Patients will also complete preoperative IKDC, Tegner, PROMIS, and VAS pain surveys. 
Measurements of thigh circumference and knee range of motion will occur at 2 week intervals post 
operatively. Strength testing will start at 6 weeks post-operatively. These measurements will occur 
during standard therapy sessions. KT 2000 and Lachman exam will be performed at 4, 6, 8, and 12 
months post operatively. A standard functional return to sport evaluation will be performed at the 4, 
6, 8, and 12 month postoperative visits. Labs for HGH, IGF, and CK will be drawn at 2, 6, 12, and 
24 weeks. VAS pain scores will be recorded before and after each therapy session. The PROMIS, 
IKDC, and Tegner surveys will be given at 4, 6, 8, 12 month intervals. The study will conclude at 
12 month follow up. All post-operative visits will be standard of care. No additional clinic visits 
will be required for this study. Background patient information will be collected including age, 
sex, BMI, and co-morbidities.   
 
b. The control group will be necessary to provide a baseline measure on which moderated blood flow 
therapy will be compared.  
 
c. Blinding of the subject will not be possible as the patient will be able to recognize if they have or 
have not had the moderated blood flow (Delfi) device applied during therapy and application of a 
sham-device is not practical or considered standard of care. Evaluators performing measurements 
will be blinded to the patient’s treatment group during assessment of muscle strength, thigh 
circumference, knee range of motion, Lachman exam, and KT2000. Surgeons will also be blinded 
to the respective treatment groups.  All other outcome measures are objective and quantitative.   
 
 
Pre-Trial 
Investigator discusses study with the patient in person or by phone and 
provides the patient with a patient Consent Form (in person or 
electronic) 

 
 
 
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Patient provides written consent or electronic consent (Patient IE e-
consent) to participate in the study 
   (randomization occurs) 
IKDC, Tegner, PROMIS, VAS surveys completed.  
Baseline thigh circumference, ROM, Lachman exam, KT2000 performed 
Baseline HGH, IGF, CK labs obtained 
Day 0   
Operative procedure: Documentation of the type of ACL graft used.  
  
Post op Day 1-completion of PT 
 
Patients begin standard physical therapy routine +/- moderated blood flow 
Thigh circumference, and knee ROM performed every 2 weeks.  
VAS pain survey recorded before and after each therapy session 
Post Op Weeks: 2, 6, 12, 24 
Labs for HGH, IGF, and CK levels obtained. Strength testing during routine 
Physical Therapy visits begins at 6 weeks 
4 months post-operatively   
Functional return to sport evaluation performed by Physical Therapy 
IKDC, Tegner, PROMIS, VAS surveys completed.  
Lachman exam and KT2000 performed.  
 
6 months post-operatively 
 
Functional return to sport evaluation performed by Physical Therapy* 
IKDC, Tegner, PROMIS, VAS surveys completed.  
Lachman exam and KT2000 performed.  
 
8 months post-operatively* 
Functional return to sport evaluation performed by Physical Therapy 
IKDC, Tegner, PROMIS, VAS surveys completed.  
Lachman exam and KT2000 performed.  
 
12 months post-operatively 
Functional return to sport evaluation performed by Physical Therapy* 
IKDC, Tegner, PROMIS, VAS surveys completed.  
Lachman exam and KT2000 performed Patient will be released from all 
study activities after the 12 month follow-up visit 
 
* If received as standard of care, data will be collected. If not, data will not be collected 
 
 
Withdrawal of Subjects: Subjects will be informed that they have the right to withdraw from the study at 
any time for any reason, without prejudice to their medical care. The Investigator(s) may elect at any time 
to withdraw a subject from the study for any reason unrelated to the study if such a decision is in the 
subject’s best medical interest. If a subject discontinues the study prematurely, or is withdrawn by the 
Investigator(s), as much follow-up data as possible will be obtained. The primary reason for termination or 
discontinuation will be documented in the report of the final results. Subjects who are withdrawn for any 
reason from the study after treatment will not be replaced.  Subjects who withdraw consent and refuse to 
complete the follow-up assessment will be considered off-study at that time. Attempts will be made to 
retrieve any follow-up data, in particular, adverse events at the time of study discontinuation. If the 
Investigator(s) reports a subject as lost to follow-up, an assistant to the Investigator will ensure that 
documentation is complete regarding the reason(s) this has occurred and will ensure that every attempt is 
made by the Investigator(s) to contact the subject or significant other persons associated with the subject to 
determine subject status. Appropriate documentation will consist of at least two documented attempts at 
contact via telephone by an assistant of the Investigator (s), followed by an attempt to contact via registered 
US mail or other courier service requiring recipient signature. 
 
 
 
 
1. 
Inclusion/Exclusion Criteria 
Inclusion Criteria: 
 
-Patients between ages 18-40 

 
 
 
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-Diagnosed with isolated ACL tear and have been indicated to undergo ACL 
reconstruction 
 
 
Exclusion Criteria: 
 
 
-age <18 years old or >40 years old 
 
 
-Multiligament knee injury 
 
 
-Revision ACL reconstruction 
 
 
-History or peripheral vascular disease 
 
 
-History of deep vein thrombosis or pulmonary embolism 
 
 
-Any contraindication to moderated blood flow restriction therapy 
 
 
-Inability to comply with post-operative ACL reconstruction rehabilitation 
 
 
-If meniscal repair or a cartilage procedure is performed at the time of surgery that 
would preclude the patient from being able to follow the standard post-operative ACL 
rehabilitation.  
 
2. 
Devices 
 
Delfi’s PTS Personalized Tourniquet System (Delfi Medical Innovations Inc.,Vancouver, Canada), 
a form of moderated blood flow training, has been used by the Missouri Orthopaedic Institute Department 
of Physical Therapy for its proven safety and effectiveness in help to promote muscular strength gains, 
enhance sports performance, and to assist with rehabilitation from injury or surgery.  
Moderated blood flow training causes increased blood pooling in the limbs. During exercise lactic 
acid is then produced. Due to the moderation of blood flow, the lactic acid is retained longer in the muscles. 
Hypoxia, acidosis, inorganic phosphate, AMP and other local factors have been shown to turn on 
transcription, and thus, protein synthesis in muscle cells. This local effect results in stimulation of muscle, 
tendon and vascular growth (5). Muscle receptors also send stronger signals to the brain which in turn 
causes large quantities of growth hormone to be released. Under the condition of moderated blood flow 
therapy, it has been shown that even short-term and low-intensity exercise can induce muscle strength, 
hypertrophy and increasing muscle mass (7-9). 
 
 
 
3. 
Study Statistics 
a. Primary outcome variable will be muscle strength determined by a trained observer blinded to 
therapy cohort and time point.  
b. Secondary outcome variables will include: thigh circumference, VAS pain scores, IKDC, 
Tegner, PROMIS surveys, knee range of motion, KT 2000, Lachman exam, lab levels of HGH, 
IGF, and CK.  
c. Number of patients per group (n=25) was determined from a pre-study power analysis (t-Test) 
using previously published data on rehabilitation after ACL reconstruction for a desired power 
of 0.8 and alpha = 0.05. This analysis resulted in recommended sample size of 20 per group.  
The N of 25 per group was chosen to allow for subjects lost to follow-up.  
 
4. 
Risks 
a. Patient confidentiality during the course of this study will be protected in compliance with HIPAA 
requirements as well as the requirements of the University of Missouri Health-Sciences IRB.  
 
After consent is obtained, all subjects will be assigned a study identification number that requires 
the use of a key in order to decipher a subject’s personal identification information. The key will be 
kept in the Cerner Power Trials database, which is password protected. The study identification 
number will be used to label all paper data collection instruments.  

 
 
 
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All subject information in electronic format will be kept in password-protected storage. All subject 
information in paper format will be kept in locked cabinets in a secured suite at the Missouri 
Orthopedic Institute or destroyed.  
 
 
b. There is potential risk of discomfort from application of the pneumatic tourniquets. This is 
temporary and occurs during the therapy sessions.  
c. Due to the venous pooling from vascular constriction, there is a theoretical risk of increased 
incidence of blood clots, vascular insufficiency, potential muscle injury, oxidative stress, and 
possible nerve conduction problems. These theoretical risks have not been demonstrated in previous 
studies specifically investigating the safety of occlusive therapy (10,11).. 
 
 
5. 
Benefits 
a. There is a potential benefit to the moderated blood flow group of increased muscle mass, 
strength, and ability to progress in therapy at an accelerated rate compared with control patients. 
If this benefit is found in the treatment group, moderated blood flow therapy may be able to be 
used in all ACL reconstruction patients. The hope is that the increased strength and muscle mass 
will allow patients to progress in therapy at a safe and accelerated rate, and therefore allow 
patients to get back to their preinjury activities. Otherwise, there are no further direct benefits to 
the patient for participation in the study.  
 
6. 
Payment and Remuneration 
a. No compensation for participation in the study.  
 
7. 
Costs 
a. Patients that choose to participate in the study will not incur any additional costs related to the 
study. Patients will receive the standard of care surgical procedure and postoperative 
rehabilitation protocols. Any additional lab tests and study related measurements will be at no 
charge to the patient and will be covered by the Department of Orthopaedic Surgery. 
 
 
8. 
References 
 
(1)Griffin, Letha Y., et al. "Noncontact anterior cruciate ligament injuries: risk factors and prevention 
strategies." Journal of the American Academy of Orthopaedic Surgeons 8.3 (2000): 141-150. 
 
(2) Iwasa, J., Y. Shima, and L. Engebretsen. "Results of ACL reconstruction." The Knee Joint. Springer 
Paris, 2012. 245-262. 
 
(3) Palmieri-Smith, Riann M., Abbey C. Thomas, and Edward M. Wojtys. "Maximizing quadriceps 
strength after ACL reconstruction." Clinics in sports medicine 27.3 (2008): 405-424. 
 
(4) KAATSU-In Layman’s Terms. http://www.kaatsu-global.com/kaatsu-in-laymans-terms/ Accessed 
11/9/15.  
 
(5) KAATSU – In Medical Terms. “Local and Systemic Mechanisms of KAATSU Training” 
http://www.kaatsu-global.com/kaatsu-in-medical-terms/ Accessed 11/5/15.  
 

 
 
 
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(6) Abe, Takashi, Charles F. Kearns, and Yoshiaki Sato. "Muscle size and strength are increased following 
walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk training." Journal of 
Applied Physiology 100.5 (2006): 1460-1466. 
(7) Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N (2000a) Rapid increase in plasma 
growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol 88: 61-65.  
 
(8) Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N (2000b) Effects of resistance 
exercise combined with moderate vascular occlusion on muscle function in humans. J Appl Physiol 88: 
2097-2106.  
 
 (9)  Abe T, Yasuda T, Midorikawa T, Sato Y, Inoue K, Kearns CF, Inoue K, Koizumi K, Ishii N (2005) 
Skeletal muscle size and circulating IGF-1 are increased after two weeks of twice daily “KAATSU” 
resistance training. Int J KAATSU Training Res 1: 6-12 
 
 
(10)Loenneke, J. P., Thiebaud, R. S. and Abe, T. (2014), Does blood flow restriction result in skeletal 
muscle damage? A critical review of available evidence. Scandinavian Journal of Medicine & Science in 
Sports, 24: e415–422. doi: 10.1111/sms.12210 
http://onlinelibrary.wiley.com/doi/10.1111/sms.12210/pdf 
 
(11)Loenneke, J. P., Wilson, J. M., Wilson, G. J., Pujol, T. J. and Bemben, M. G. (2011), Potential safety 
issues with blood flow restriction training. Scandinavian Journal of Medicine & Science in Sports, 21: 510–
518. doi: 10.1111/j.1600-0838.2010.01290.x 
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0838.2010.01290.x/full