Effect of Different Injection Regimens of Autologous Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis
Phase: PHASE2
Conditions: Knee Osteoarthritis
Sponsor: Andrews Research & Education Foundation

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of 
Autologous Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis 
 
Date: 06/19/2019 
NCT03889925 
 
 
 

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of Autologous 
Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis  
Adam Anz, M.D. 
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Title:  A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of 
Autologous Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis 
 
Principal Investigator:  
Adam Anz, M.D.  
 
Co-Investigators:  
 
Roger Ostrander, M.D. 
 
 
 
 
Steve Jordan, M.D. 
 
 
 
 
Christopher O’Grady, M.D. 
 
 
 
 
Brett Kindle, M.D. 
Hillary Plummer, PhD, ATC 
 
Funding Mechanism:   
In-House 
 
Institution(s):   
 
Andrews Institute 
 
 
 
 
1040 Gulf Breeze Pkwy. 
 
 
 
 
Gulf Breeze, FL 32561 
 
 
 
 
(850) 916- 8761 
 
 
 
 
 
 
 
 

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of Autologous 
Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis  
Adam Anz, M.D. 
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1 
Background / Scientific Rationale 
In the United States it is estimated that 47 million people have been diagnosed with arthritis. 4.3 
million have been diagnosed with isolated osteoarthritis of the knee and knee arthritis accounts 
for 20% of disability claims [1]. Prevalence of the disease continues to climb and is expected to 
double by 2030. In addition, 4 out of 5 patients with osteoarthritis have movement limitations 
[1]. Currently there are no curative treatments for osteoarthritis. Surgical options include 
arthroscopy, osteotomies, and total joint replacement, but not all patients with knee osteoarthritis 
are candidates for surgical treatments, and others choose non-operative treatments instead of 
undergoing a procedure. Non-surgical treatment options include medications such as non-
steroidal anti-inflammatory’s (NSAIDs), injectables such as corticosteroids and hyaluronic acid, 
or physical treatments such as rehabilitative therapy, unloading braces, and activity 
modifications (i.e. canes or walkers). Additionally, weight loss can help in the battle to reduce 
pain in cases of knee osteoarthritis. 
The clinical efficacy of hyaluronic acid or corticosteroid injections has been reported, but effects 
are short lived. This has led to the development of additional injection options such as 
autologous derived blood products which have been documented to alleviate symptoms related to 
knee osteoarthritis, with recent comparative studies suggesting a greater, long-lasting effect with 
these blood derived products like platelet rich plasma (PRP) [2-8]. One clinically-developed 
preparation of platelet rich plasma, named autologous conditioned plasma (ACP), has 
randomized controlled trial data proving efficacy [4,9].  Clinical use of platelet rich plasma for 
knee arthritis typically involves a 3-injection series over 3 weeks, i.e. an injection once a week 
for three weeks. Currently, all three orthopedic providers in this study use ACP to treat patients 
with knee osteoarthritis in common accepted clinical practice.  
2 
Objectives 
The main objective of this study is to determine if hyaluronic acid (HA) injected at the same time 
as autologous conditioned plasma (ACP), a leukocyte-poor platelet rich plasma product, will 
improve the performance of ACP in the treatment of symptomatic knee osteoarthritis. We 
hypothesize that the injection of hyaluronic acid will improve the efficacy of ACP.  
3 
Participant Eligibility 
Inclusion Criteria: Patients between the ages of 30 and 80 who have documented radiographic 
evidence of OA in the tibiofemoral or patellofemoral compartment of the target knee (Kellgren-
Lawrence grades 1-4) will be screened for participation in this study. Patients must have a 
documented diagnosis of primary OA for at least 6 weeks.  

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of Autologous 
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Adam Anz, M.D. 
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Exclusion criteria: Patients who have had viscosupplementation in the involved knee in the past 
6 months. Any patient who has had a corticosteroid injection in any joint within 3-months prior 
to screening will be excluded. Patients with gout or rheumatologic disease will be excluded. 
Patients who have had a previous negative experience with HA. Any patient who will have 
difficulty obtaining internet access, does not have an active e-mail address, or is unable to 
comprehend study documents or give informed consent will be excluded.  
4 
Participant Enrollment 
80 patients will be recruited through the Andrews Institute physician practices. Potential 
participants will be prescreened for inclusion and exclusion criteria through standard of care 
medical evaluations. Once a potential participant has agreed to be involved in the study, they will 
go through the described informed consent process. Patients meeting the inclusion criteria will 
have the study explained to them by one of the members of the investigating team, and they will 
be given an opportunity to participate if they are interested. No specific advertising or 
recruitment material will be utilized.  
Participant will also be instructed that they must not take any prescription or over the counter 
non-steroidal anti-inflammatory drugs (NSAIDS) for 1 week prior to the first injection until after 
the final injection. The participants will then be randomly placed in one of the two study groups 
and be scheduled to receive a three-injection series of autologous conditioned plasma injection or 
a two-injection series of autologous conditioned plasma and hyaluronic acid and a third injection 
on the third week of ACP in their involved knee. For The group receiving autologous 
conditioned plasma and hyaluronic acid, HA will be an additional injection on the first two 
injections and the third injection will be ACP alone. This regimen was selected to reflect the 
current evidence-based regimens for ACP and HA independently. 
 
5 
Study Design and Procedures 
Study design will be randomized control trial. Participants who meet the inclusion criteria will 
have the study explained in detail and informed consent will be obtained as outlined above. 
Participants will complete patient reported outcome questionnaires prior to their injection. The 
questionnaires will include the Western Ontario and McMaster University‘s Osteoarthritis Index 
(WOMAC), International Knee Documentation Committee Subjective Knee Evaluation Form 
(IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS). The WOMAC is 24 questions 
and takes approximately 2-5 minutes, the IKDC is 19 questions and takes 3-5 minutes, and the 
KOOS is 42 items and takes approximately 5-10 minutes. Participants will also complete these 
questionnaires at 1, 3, 6, 12, 18, and 24 months after the final injection.   

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A trained medical professional will draw blood from the patients arm and the blood will be spun 
in a centrifuge for 5 minutes at 1500 RPM. The platelets will then be separated off for injection 
into the patient’s knee. The treating physician will then inject the ACP into the involved knee 
joint following standard aseptic technique per the physician’s standard of care. This entire 
process will be completed in a single patient visit. Any unused portion of a sample in the 
physician’s office will be disposed of through standard biohazard waste disposal systems as 
required by law. 
Group 1 [ACP]: Will receive 3 intra-articular injections of autologous conditioned plasma dosed 
at once a week for 3 weeks. Group 2 [ACP-HA]: Will receive 2 intra-articular injections of 
autologous conditioned plasma and hyaluronic acid once a week for 2 weeks and a third injection 
on the third week of ACP. 
  
6 
Expected Risks and Benefits 
 
Risks and Discomforts: Potential risks include those expected with any injection 
including syncope, dizziness, headache, nausea, tachycardia, infection (septic arthritis, phlebitis, 
and osteomyelitis), bleeding, or pain. Additionally, participants may experience knee stiffness or 
inflammation associated with the procedures. These risks would not be any higher with the test 
interventions than those patients are subject to with injection treatments of knee OA. As with 
any research involving patients there is the inherent risk of a breach in patient confidentiality 
though this will be minimized through the use of participant code numbers and adherence to all 
HIPAA guidelines.  
 
Benefits: Direct benefits of the study include injections that may provide potential pain relief, 
improvement of knee function, and improvement of quality of life, which all could lead to the 
avoidance of surgical intervention. It is also believed that the information obtained in this study will 
help advance treatment of osteoarthritis through the use of regenerative medicine. 
 
7 
Data Management Procedures 
All personal information is strictly confidential and no names will be disclosed except as 
required by law. All information and data collected during this research will be recorded in a 
spreadsheet. This spreadsheet will not contain protected health information. The spreadsheet will 
be stored in a secure password protected folder on a laptop that only the study Investigators will 
have access to and will be permanently deleted following publication of any and all manuscripts, 
if any, written as a result of this research. Records related to this study will be securely retained 

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of Autologous 
Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis  
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in a secure location for a period of 3 years after the completion of the study or longer as required 
by law. At that time, all records will be properly destroyed.  
8 
Data Analysis 
All data will be entered into Surgical Outcomes System (SOS) & Research Electronic Capture 
Database (REDCap) and descriptive data will be compiled. 
9 
Statistical Considerations 
A power analysis was performed to determine sample size based upon recent clinical trials 
comparing PRP to HA for the treatment of osteoarthritis. Analysis utilized the average of 
standard deviation to detect average of group mean effect at 80% power. This determined that 25 
patients per group would be needed to reach statistical significance with the WOMAC.  
Ranges, means and standard deviations for all measures will be determined and calculated. Data 
will be analyzed for differences between groups using a repeated measures ANOVA design, 
using a significant p-value of < 0.05 for rejecting the null hypothesis.   
10  
Quality Control and Assurance 
All protocols will be monitored and analyzed data will be checked for accuracy by the principal 
investigator and /or a designated AREF research team member. All medical data will be kept in 
compliance with HIPAA guidelines. 
11 
Regulatory Requirements 
 
Informed Consent: 
The informed consent process will be performed by one of the study investigators or staff, in the 
office. All participants will have the study described to them and will give as much time as they 
require to read an approved, stamped version of the informed consent document. After signing of 
the informed consent document, participants will be given a copy for their records. This process 
will take place only after the patient has consented to proceed with the study. 
 
Participant Confidentiality: 
Participant confidentiality information is listed above in #7 (Data Management Procedures). All 
medical data will be recorded and stored in compliance with HIPAA guidelines. 
12 
References 

A Randomized, Control Clinical Trial:  The Effect of Different Injection Regimens of Autologous 
Conditioned Plasma for the Treatment of Symptomatic Knee Osteoarthritis  
Adam Anz, M.D. 
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1.  Hootman JM, Helmick CG.  Projections of US prevalence of arthritis and associated activity 
limitations. Arthritis Rheumatology. 2006; 54: 226-9. 
 
2.  Spakova T, Rosocha J, Lacko M, Harvanova D, Gharaibeh A. Treatment of knee joint osteoarthritis 
with autologous Platelet-Rich Plasma in comparison with hyaluronic acid. American Journal of 
Physical Medicine & Rehabilitation. 2012;91(5):411-417. 
 
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hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to 
osteoarthritis. Arthroscopy. 2011;27(11):1490-1501. 
 
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Medicine. 2012;40(12):2822-2827. 
 
5.  Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more 
effective than placebo for knee osteoarthritis: A prospective, double-blind, randomized trial. American 
Journal of Sports Medicine. 2013;41(2):356-364. 
 
6.  Li M, Zhang C, Ai Z, Yuan T, Feng Y, Jia W. Therapeutic effectiveness of intra- knee- articular 
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and Reconstructive Surgery. 2011;25(10):1192-1196. 
 
7.  Filardo G, Kon E, Di Martino A, et al. Platelet-rich plasma vs hyaluronic acid to treat knee 
degenerative pathology: study design and preliminary results of a randomized controlled trial. BMC 
Musculoskeletal Disorders. 2012;13. 
 
8.  Vaquerizo V, Plasenicia M, Arribas I, et al. Comparison of intra-articular injections of plasma rich 
in growth factors (PRGF-Endoret) versus Durolane hyaluronic acid in the treatment of patients with 
symptomatic osteoarthritis: A randomized controlled trial. Arthroscopy. 2013; 29 (10): 1635-1643 
 
9.  Smith P.  Intra-articular Autologous Conditioned Plasma Injections Provide Safe and 
Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, 
Placebo-controlled Clinical Trial.  American Journal of Sports Medicine. 2016;44(4):884.891.