Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers in Patients With Acute Anterior Cruciate Ligament Tears
Phase: PHASE2
Conditions: Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture
Sponsor: Andrews Research & Education Foundation

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
Adam Anz, M.D. 
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Title:  Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative 
Biomarkers in Patients with Acute Anterior Cruciate Ligament Tears   
 
Principal Investigator:  
Adam Anz, M.D.  
 
Co-Investigators:  
 
Steve Jordan, M.D. 
Brett Kindle, M.D. 
Roger Ostrander, M.D.   
 
 
 
 
 
Funding Mechanism:   
In-House 
 
Institution(s):   
 
Andrews Institute 
 
 
 
 
1040 Gulf Breeze Pkwy. 
 
 
 
 
Gulf Breeze, FL 32561 
 
 
 
 
(850) 916- 8570 
 
 
 
 
 
 
 
 
 
1 
Background / Scientific Rationale 

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
Adam Anz, M.D. 
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In the United States, 80,000 anterior cruciate ligament (ACL) ruptures are estimated to 
occur annually, with an increased likelihood of these injuries involving individuals participating 
in sports and aged between 15-25 years [7]. A potential long-term consequence of ACL injuries 
is the development of posttraumatic osteoarthritis (PTOA) in the years following injury [8,9]. 
There are no curative treatments for osteoarthritis, increasing the importance of minimizing the 
occurrence of PTOA following ACL injuries. Current literature has begun to indicate that 
biochemical changes in the knee joint cartilage, such as chondrocyte death, following injury can 
contribute to the development of PTOA [10-12]. 
 
A non-surgical treatment option for the management of osteoarthritis include injectables such 
as corticosteroids and platelet rich plasma (PRP). These injectables work by positively affecting 
cartilage cells, also known as chondrocytes, and the cells of the joint lining tissue, also known as 
synoviocytes.  PRP is an autologous derived blood product, i.e. a joint injectable made from the 
patient’s own blood at the time and location of injection with simple blood centrifugation.  
Studies in the bench-top laboratory setting have provided in-vitro evidence that PRP decreases 
synoviocyte production of metallometal proteases, an inflammatory protein with negative effects 
on cartilage, decreases the effects of inflammatory proteins such as IL-B on chondrocytes, and 
has an anti-inflammatory effect upon the gene expression of chondrocytes and synoviocytes[14-
16]. While these are mechanisms that can help manage osteoarthritis after it arises, they also are 
mechanisms that could help prevent osteoarthritis before it forms. Recent comparative studies of 
PRP to other injectables in the management of osteoarthritis suggest a greater, long-lasting effect 
of PRP than other injectables [1-6]. 
 
Orthopedic research has focused on methods to prevent PTOA after ACL injury.  Recent 
study involving the post-injury ACL joint milieu suggested that an early intervention of joint 
aspiration and corticosteroid injection has positive effects, including a decrease in biomarkers 
responsible for chondral degeneration [13]. This combined with in vitro study on the effects of 
PRP on chondrocyte and synoviocyte activity suggest that PRP has potential to affect the ACL-
injured joint. However, current literature is lacking in regard to this assertion, and in vivo study 
of PRP to positively affect the joint after following ACL injury is warranted. 
2 
Objectives 
The main objective of this study is to determine if an early intervention of joint aspiration and 
PRP injection will positively affect the biomarkers representative of chondral degeneration in 
patients with ACL injuries. We hypothesize that the intervention will reduce the volume of 
inflammatory and chondrodegenerative biomarkers following ACL injury.  
3 
Participant Eligibility 
Inclusion Criteria: Patients between the ages of 14 and 40 years with closed growth plates as 
visualized on plain radiography, no history of previous traumatic ipsilateral knee injury, and no 

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
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clinical evidence of posterior cruciate ligament injury with no more than grade 1 medial or 
lateral collateral ligament injury.  
Exclusion criteria: Patients without a palpable knee effusion, an injury occurring more than 10 
days before enrollment, previous ipsilateral knee surgery, intra-articular cortisone or PRP 
injection into either knee within 3 months of injury, participation in another clinical drug trial 
within the 4 weeks before injury, and a history of any inflammatory disease or immune-
comprised. 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 
60 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.  
The participants will then be randomly placed in one of the two study groups and be scheduled to 
receive either an injection of PRP or no injection in their involved knee.  
Participants will not be billed for the joint aspirations or PRP injections.  
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.  
Patients will be randomized to 1 of 2 groups. Both groups will have joint aspirations performed 
at an initial visit, within the first 10 days after injury, and at the time of surgery, within 4 weeks 
of injury. Group 1 will receive only joint aspirations as outlined above.  Group 2 will undergo 
aspirations as outlined above and also receive a PRP injection at the initial visit and at a second 
visit 5-12 days after the initial visit.  Joint aspirations and injections will be performed through 
the superolateral, suprapatellar approach Patients will be instructed not to take any prescription 
or over-the-counter nonsteroidal anti-inflammatory medications. Patients will be encouraged to 
rest, ice, and elevate their injured knee. 

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
Adam Anz, M.D. 
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PRP Manufacturing: PRP preparation will involve Autologous Conditioned Plasma disposables 
(Arthrex, Naples, FL, USA), a commercially available kit for the production of PRP.  
Preparation will follow the manufacturer’s instructions. The treating physician will then inject 
the PRP 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. A 0.1-0.5 mL 
sample of the PRP will be inserted into a vacutainer for analysis of cell count.  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.  
Biomarker Analysis: Samples will be prepared and frozen at -80 C until all study sample have 
been obtained. Enzyme-linked immunosorbent assay kits will be used to assess 
chondrodegenerative & synovial fluid biomarkers.  
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 PRP injection. Knee aspiration and injection are standard 
medical procedures used routinely in the management of knee osteoarthritis and acute injury.  
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 potential pain relief, improvement of knee 
function from joint aspiration, and the potential to decrease the risk of PTOA after ACL injury. It is 
also believed that the information obtained in this study will help advance treatment of PTOA 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 
REDCap and exported into 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 in a secure location for a period of 3 years after the 

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
Adam Anz, M.D. 
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completion of the study or longer as required by law. At that time, all records will be properly 
destroyed.  
8 
Data Analysis 
This study is anticipated to take 2 years to complete. All data will be entered into REDCap. The 
investigators will meet at appropriate intervals to evaluate and analyze the data.  
9 
Statistical Considerations 
A power analysis was performed to determine sample size based upon recent clinical trials. 
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. 10 additional patients will be account for potential patient withdrawal or lost-to-
follow-up. 
Ranges, means and standard deviations for all measures will be determined and calculated. Data 
will be analyzed for differences between groups using a t-test 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. 

Effect of Platelet Rich Plasma Injections on Inflammatory and Chondrodegenerative Biomarkers 
in Patients with Acute Anterior Cruciate Ligament Tears   
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12 
References 
 
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2. Kon E, Mandelbaum B, Buda R, et al.  Platelet-Rich Plasma intra-articular injection versus 
hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early 
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more effective than placebo for knee osteoarthritis: A prospective, double-blind, randomized 
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degenerative pathology: study design and preliminary results of a randomized controlled trial. 
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in Patients with Acute Anterior Cruciate Ligament Tears   
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