Clinical trial NCT05080075: Platelet Rich Plasma in Knee Osteoarthritis
Official title: Platelet Rich Plasma in Knee Osteoarthritis: Establishing Clinical Guidelines to Predict and Maximize Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Knee Osteoarthritis
Keywords: Platelet rich plasma
PRP
Knee osteoarthritis
Platelet concentration
Lead sponsor: University of Toledo
Sponsor class: OTHER
First posted: 2021-10-15
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study involves a single group, all of whom will be receiving the same treatment (platelet rich plasma injection into the knee)
Primary purpose: TREATMENT

Brief summary: In this study, the investigators will be performing intra-articular platelet rich plasma (PRP) injections for patients experiencing pain related to osteoarthritis of the knee. The investigators will be following clinical outcomes, and how they relate to concentrations of the PRP samples as well as following opioid and emergency room utilization pre and post-injection.

Detailed description: Osteoarthritis is the most common form of arthritis and results in pain and stiffness in the affected area and, depending on the joint, can lead to difficulty with mobility as well as with performing basic activities of daily living. Conservative management of this condition includes physical therapy, activity modification, bracing, medications, and corticosteroid injections. When conservative treatment measures have failed, patients are often left with a choice between surgery, specifically total knee arthroplasty, and long-term pain medications, including opioid medications. In the midst of the opioid epidemic, physicians are seeking non-opioid alternatives for treating pain when other conservative treatments have failed. One such alternative treatment option is an intraarticular platelet rich plasma (PRP) injection.

The goal of PRP is to stimulate the body's existing regenerative capabilities. Since it is known that platelets play a key role in the body's natural healing processes, multiple clinical trials have been conducted to determine if injecting the affected joint with a platelet rich sample of their own blood promotes healing and thus improves pain and function for patients suffering from osteoarthritis. The studies involving PRP have yielded some promising outcomes, however much remains unknown about maximizing outcomes using this technology and a clear and defined protocol for this intervention does not yet exist.

This study aims to clarify some of the factors that affect clinical outcomes, such as platelet and cell concentrations (both in a serum sample and in the centrifuged PRP sample) and patient demographics. Determining if higher platelet counts in the serum sample are associated with better outcomes could potentially be used to prognosticate patient outcomes and candidacy for the procedure. The investigators are examining if PRP injections reduce the costly utilization of emergency room care and use of opioid pain medications before and after the procedure. The investigators are correlating how specific PRP cell and substance concentrations (platelet, monocytes, etc.) affect clinical outcomes as well. Ultimately, our hope is that this study will contribute to the growing evidence that PRP is a safe and effective treatment option for debilitating knee osteoarthritis, that it can improve pain and function and reduce opioid use and emergency room utilization.

This study takes place at the University of Toledo Physical Medicine and Rehabilitation outpatient clinic. 50 subjects is the minimum required to answer the aims of this study but 100 will be the target number for this study over the course of one year. Members of the study will be recruiting patients by informing physicians in the area about the study and requesting referrals to the clinic for anyone that might meet criteria and expresses interest in the study (focusing on orthopaedics, rheumatology, internal medicine and family medicine). Study members will also be sending out brochures to inform local health care providers as well as the surrounding public about the study, and information on how to arrange a clinic visit to evaluate candidacy. Brochures may be sent in the form of paper copies, FAX or email with an attached brochure. Additionally, the investigators will be informing patients already established with providers from our clinics about the study. These patients may be contacted at any of the physicians' sites of service.

Patients meeting criteria, including documented knee osteoarthritis and associated pain, will have pre and post intra-articular PRP injection visits where information will be gathered for future analysis. The patient will initially be asked to come in to the Physical Medicine and Rehabilitation clinic after expressing interest in being a part of the study. During that initial visit, the patient will be given the initial screening form with inclusion criteria and exclusion criteria and it will be determined if they are a candidate for the study. If they do meet the criteria for inclusion, they will then be informed of the risks and benefits of the study as well as what would be required of them should they choose to enroll. The patient will then be given the consent form. If the patient signs the consent form and would like to join the study, the investigators will schedule a follow-up visit which will include the injection. At that visit, the patients who are physically able to bear children will be screened for pregnancy with a urine pregnancy test. Once the pregnancy tests are confirmed negative, they, along with all other patients, will be given the initial surveys to fill out including a review of their past medical history, the Visual Analog Scale (VAS) pain score questionnaire, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire. Once the patients have filled these all out, they will undergo a blood draw of approximately 60 mL of their blood. Some of this sample will then be sent up to a lab where a complete blood count will be run. The remaining portion of the sample will be used for preparation of the platelet-rich plasma (PRP) using the Tortland Protocol developed by Paul Tortland, DO. After centrifugation, the PRP will be loaded into a syringe to be injected into the patient's knee. During preparation of the PRP, small samples will be obtained from the whole blood, PRP, and concentrated PRP while in the biosafety cabinet and analyzed for quantification of the cell types present and for characterization of the platelets (activation status, functionality assays). All immunology lab space stated on this protocol is BSL2 certified for use of untested human blood products. Once the concentrated PRP is obtained it will be brought back to the clinic for the injection.

While the patient is waiting for the platelet-rich plasma to be prepared, the Timed-Up-and-Go (TUG) test will be performed in the clinic to assess the patient's baseline functional ability prior to receiving the injection. Within 1 hour of the patient providing the sample of blood, the platelet-rich plasma sample will be brought back down from the lab. At that time, the patient will be brought to an exam room and the platelet-rich plasma injection will be performed on the affected knee under ultrasound-guidance. A trained physician will perform the injection using a 2.5 inch, 22-gauge needle and freeze spray will be used as a topical anesthetic for the 4-6 mL injection of platelet-rich plasma into the affected knee.

Post-procedure, the patient will be contacted to set-up a 4 week, 3 month, 6 month, and 1 year follow-up appointment at which time they will be brought back into the Physical Medicine and Rehabilitation clinic. At the 4 week appointment, the patient will be filling out a post-injection survey to explain if they experienced any adverse effects from the injection. In addition, the patient will have the opportunity at this appointment to ask any questions or voice any concerns that may have come up after the injection. At the 3 month, 6 month, and 1 year appointments, the patients will fill out post-injection surveys (Post-Injection Medical Survey) regarding Emergency Department and opioid medication utilization since the injection as well as updated VAS pain score and WOMAC questionnaires. The patient will also have the TUG test performed again during these appointments. After the 1 year follow-up, the patient will no longer be followed for purposes of this study. It is important to note that only treating physicians and nurses, medical students obtaining consent, and medical assistants rooming patients will see identifiable information. All other study related data or information will be de-identified using a number system. All study personnel will be informed that information, included protected health information, is confidential.

The results from the follow-up appointment will be compared to the patient's baseline results using the key code to match the de-identified information. These will results will all be compiled into the data collection spreadsheet. Descriptive statistics will be used to summarize the patients' clinical scores by demographic variables. Repeated measures ANOVA will be used to test for changes in VAS pain score, Timed Up and Go, Opioid utilization, Emergency Room Utilization and WOMAC questionnaires over time.

Eligibility criteria: Inclusion Criteria:

* Knee pain or swelling that has been present for greater than 3 months
* Knee pain greater than or equal to 3 out of 10 on the visual analog scale
* Previous radiological evidence (X-ray) of osteoarthritis
* Age 18 or older

Exclusion Criteria:

* Unable to provide consent for enrollment in the study
* Unable to avoid NSAIDs during the study (must stop 7 days before injection)
* Age less than 18
* Confirmed rheumatologic disease affecting the knee
* Significant trauma to the knee within 2 months that resulted in pain and/or swelling
* Active malignancy
* Pregnancy
* Local injections to the knee within the last 3 months
* Previous knee surgery
* Other causes of knee pain (nerve pain, referred pain, infection of the knee joint, etc)
* History of platelet disorder
* History of thrombocytopenia
* History of severe anemia
* Severe cardiovascular disease
* Active infection
* Immunosuppression/immunodepression
* Currently taking anticoagulant/antiaggregant
* History of severe psychiatric disorder with psychosis
* Assistive device required for household ambulation within the previous 3 months
* Current IV drug user

Additionally this study requires that, for safety purposes, enrolled patients live within 2 hours driving distance from the study site.

Primary outcomes:
measure: Initial Pain outcomes
timeFrame: Start of the study, pre-injection
measure: Pain outcomes, 3 months
timeFrame: 3 months
measure: Pain outcomes, 6 months
timeFrame: 6 months
measure: Pain outcomes, 1 year
timeFrame: 1 year
measure: Functional status outcomes using the Western Ontario and McMaster University Arthritis Index (WOMAC), initial
timeFrame: Start of the study, pre-injection
measure: Functional status outcomes using the Western Ontario and McMaster University Arthritis Index (WOMAC), 3 months
timeFrame: 3 months
measure: Functional status outcomes using the Western Ontario and McMaster University Arthritis Index (WOMAC), 6 months
timeFrame: 6 months
measure: Functional status outcome using the Timed up and go (TUG) test, initial
timeFrame: Start of the study, pre-injection
measure: Functional status outcome using the Timed up and go (TUG) test, 3 months
timeFrame: 3 months
measure: Functional status outcome using the Timed up and go (TUG) test, 6 months
timeFrame: 6 months
measure: Functional status outcome using the Timed up and go (TUG) test, 1 year
timeFrame: 1 year
measure: Correlation of outcomes with whole blood and platelet rich plasma (PRP) concentrations
timeFrame: Through study completion, 1 year
Secondary outcomes:
measure: Opioid utilization, initial
timeFrame: Start of the Study, pre-injection
measure: Opioid utilization, 3 months
timeFrame: 3 months
measure: Opioid utilization, 6 months
timeFrame: 6 months
measure: Opioid utilization, 1 year
timeFrame: 1 year
measure: Emergency room utilization, initial
timeFrame: Start of the study, pre-injection
measure: Emergency room utilization, 3 months
timeFrame: 3 months
measure: Emergency room utilization, 6 months
timeFrame: 6 months
measure: Emergency room utilization, 1 year
timeFrame: 1 year
measure: Correlation of outcomes and patient demographics and co-morbidities
timeFrame: Through study completion, 1 year
Other outcomes:
Locations:
city: Toledo
country: United States
facility: University of Toledo, Health Science Campus
state: Ohio
Study officials:
affiliation: University of Toledo
name: Christian Wuescher, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Toledo
name: Ashley Schneider, MD
role: STUDY_DIRECTOR
affiliation: University of Toledo
name: Leah Wuescher, PhD
role: STUDY_DIRECTOR
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