Platelet Rich Plasma Injections In Young And Old Human Subjects (PRP-KOBE)

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 2

Conditions: Musculoskeletal Disorders; Osteoarthritis; Articular Cartilage

Treatments: Drug: Platelet-Rich Plasma (PRP) Injections; Drug: Control saline injection; Device: Centrifuge

Study type: Interventional

Funder types: Other

Identifiers

NCT06451120

22-38279

Details and patient eligibility

About

This is a randomized, double-blind, placebo-controlled phase 2 study with a secondary crossover phase at the end of the initial trial to ensure all subjects receive one PRP injection. The goal is to identify what proteins change in the blood following repeated intraarticular knee PRP injections in patients with knee osteoarthritis. The objective is to determine the protein changes resulting from a single autologous PRP injection (5 mL) in comparison to a normal saline control.

About 60 subjects will take part in this study by two age groups at UCSF into the following arms: Arm A: PRP injection; Arm B: normal saline injection control. The study aims to demonstrate what benefits PRP has on knee osteoarthritis and methods to best achieve biologic effects. Subjects with a diagnosis of knee osteoarthritis ages 18-45 and 46-70 years old presenting to a University Based sports medicine clinic will be screened for potential eligibility. Subjects who meet all qualifying requirements will be recruited from UCSF's orthopedic and primary care clinics.

Subjects will be on study for up to 26 weeks Screening: up to 14 days Treatment: injection of PRP or normal saline; subjects can cross over at week 12 to a PRP if originally in the control injection group Follow-up: 2 weeks post-baseline injection, 12 weeks postbaseline, (14 weeks if crossover patient), 26 weeks.

Full description

This is a randomized, double-blind, placebo-controlled trial with a secondary crossover phase at the end of the initial trial to ensure all subjects receive one PRP injection. The randomization will be stratified by two age groups (ages 18-45 yrs. and 46-70 yrs).Screening and medical chart data will be reviewed to determine subject eligibility.

Platelet rich plasma (PRP) falls under transfusion medicine which has been FDA approved. Seeking to identify biological pathways by which PRP acts in a degenerative condition like knee osteoarthritis. The study compares the immediate and delayed variations in blood and synovial fluid biomarkers following PRP knee intraarticular injections in younger and older patients with knee osteoarthritis. The differences in blood biomarkers between ages of Knee osteoarthritis (KOA) patients are being investigated in this study. Intra-individual variations in some blood proteins will deviate (e.g., be larger or lower) from a normal saline control between week two and week twelve following the 5 mL PRP injection.

The unblinded research evaluation will evaluate the first batch of the first 20 blood and synovial fluid samples to ensure that the tests provide the desired results and data outcomes.

The visits consist of the Baseline visits (Week 0), the Week 2 visit, and the Week 12 visit and for half of the participants an optional 14 Week visit. These are in person visits. There are three remote visits at Week 26, Week 52 and Week 104.

Participation is estimated to take 2-2.5 hours for each visit over 6 months. The time it takes for each participant to attend an on-site visit is approximately 2-2.5 hours in total each time. The knee injection takes approximately 45 minutes for blood or knee fluid donation and preparation of the PRP. This injection occurs 1-2 times, depending on randomization arm). Subjects will complete surveys at the 3-4 timepoints, estimated to take 30 minutes per timepoint (or total); perform functional testing which is walking 40 meters back and forth quickly, sitting and standing for 30 seconds, and climbing stairs for 3 minutes and have the activity monitor put on (15 minutes). Subject will complete study questionnaires at the beginning of each visit (30 minutes). In addition, participants are asked to engage in physical therapy ideally once a week for 10 weeks although this will be documented as it is standardized but not required for the study.

If subjects are assigned to the Placebo Arm (Arm B), subjects will be informed that of receiving the placebo (normal saline injection) rather than the PRP injection. Subject will be offered the option of crossing over to receive a PRP injection. If a subject agrees to have a PRP injection, researchers will collect research blood (about 60cc or 4 tablespoons) and fluid from the knee joint space. If the subject decides to receive the PRP injection, the researchers will collect research blood (approximately 20ml or 1.5 tablespoons) and fluid from the knee joint space (45 minutes). The subject will fill out a questionnaire (30 minutes) and perform tasks to test their function (45 minutes). At the baseline appointment, subjects will receive an activity monitor to use for one week. The activity monitor should be returned on the week 14 visit.

Week 14 on site visit - If subjects are given a PRP injection at 12 weeks, subjects will have a two-week follow-up visit. The researchers will collect research blood (about 20ml or 2 tablespoons) and fluid from the knee joint space. Subjects will complete a questionnaire, and tasks testing the subject's function. Subjects will go home with an activity monitor that subjects will be asked to wear for 1 week. The activity monitor should be returned. Subjects will be asked to keep a diary to record symptoms and pain medication intake following injections. The participants will be interviewed and have their diaries reviewed on follow up visits.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Grade 1-3 KL score will be recruited;
2. Symptoms of knee osteoarthritis for at least 3 months before presentation in one knee;
3. Have symptomatic complaints from osteoarthritis pain in no other joint affecting the hips, ankles or unaffected knee;
4. Will be able to attend and perform physical therapy.
5. English-speaking

Exclusion Criteria

1. Patients will be excluded if:

2. Received injection therapy for knee osteoarthritis in the past 6 months

3. Have signs of concomitant osteoarthritis of 1 or more other major joints of the lower extremities that impair their daily activity level

4. History of septic arthritis

5. Have underwent a previous knee surgery specifically for osteoarthritis or osteochondral defects less than 1 year before randomization (i.e. autograft or allograft surgery

6. High tibial osteotomy, partial knee replacement, patellar resurfacing), total knee replacement or existing surgical hardware in the knee

7. Patient with platelet disorders, bleeding disorder

8. Patient with rheumatologic disease, automimmune disorder, immunocompromised status, active history of cancer

9. Patient taking Chemotherapy, need for regular prednisone or antiinflammatory used

10. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.

11. Uncontrolled illness, physical disability, or other contraindication to aerobic exercise training including, but not limited to:

i. Acute myocardial Infarction (within 5 days of any planned study procedure); ii. Unstable angina; iii. Uncontrolled arrhythmia causing symptoms or hemodynamic compromise; iv. Recurrent syncope; v. Active endocarditis; vi. Acute myocarditis or pericarditis; vii. Symptomatic severe aortic stenosis; viii. Uncontrolled heart failure; ix. Acute (within 3 months) pulmonary embolus or pulmonary infarction; x. Thrombosis of lower extremities; xi. Suspected dissecting aneurysm; xii. Uncontrolled asthma; xiii. Pulmonary edema; xiv. Room air desaturation at rest ≤85%; xv. Respiratory failure; xvi. Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (ie infection, renal failure, thyrotoxicosis); and xvii. Mental impairment leading to inability to cooperate.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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60 participants in 2 patient groups, including a placebo group

Platelet-rich plasma (PRP)

Experimental group

Description:

A vacutainer vial containing 50 mL of peripheral blood will be processed immediately to create PRP using a previously optimized two-step centrifugation protocol viii. First, the whole blood will be centrifuged at 500 x g for 8 minutes at 4°C. The plasma will be collected above the buffy coat using a sterile pipette, placed into a separate sterile tube, and centrifuged a second time at 700 x g for 17 minutes at 12° C. The top 70% will be collected as the PPP and the bottom 30% will be resuspended as the PRP. PPP will be aliquoted into cryovials for storage at -80 °C. Approximately 6 mL of PRP will be produced from each 50 mL vial of whole blood. Five mL will be allocated for administration to patients and the remaining one mL will be aliquoted into cryovials for storage at -80 °C. The syringe containing PRP will be covered with Aluminum foil, such that the investigator cannot tell what fluid is to be injected.

Treatment:

Device: Centrifuge

Drug: Platelet-Rich Plasma (PRP) Injections

Control saline injection (wait-list control)

Placebo Comparator group

Description:

A placebo injection of 6 mL of 0.9% saline will be prepared by the unblinded research assistant in an adjacent room. The syringed will be prepared in a 10 mL syringe and covered with Aluminum foil, such that the investigator performing the injection cannot tell if there is PRP or saline to be injected.

Treatment:

Drug: Control saline injection

Drug: Platelet-Rich Plasma (PRP) Injections