Pilot Synovial Fluid Molecular/Stem Cell Response to PRP in Knee Osteoarthritis: Clinical & Imaging Outcome Correlation

Synovial Fluid Biomarker and Mesenchymal Stem Cell Response to PRP in Knee Osteoarthritis With Clinical and Imaging Outcome Correlation: Proof of Concept Study

The purpose of this study is to evaluate the affect that platelet rich plasma has on the molecular an cellular functioning of the knee joint.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Biological: Platelet Rich Plasma; Other: Normal Saline

Detailed Description

In this study 18 subjects with mild to moderate symptomatic knee osteoarthritis will be recruited per an IRB approved protocol with explicit inclusion and exclusion criteria. Subjects who are enrolled and meet all criteria will be blinded and randomized (2:1) to receive Platelet Rich Plasma or normal saline "control". Prior to the intervention, a synovial fluid aspiration will occur. At follow up number one (approximately 10 days from baseline) a repeat aspiration will occur and a differential analysis of the molecular and biochemical effects will be undertaken; this data will serve as the primary outcome measures. This data will be correlated to clinical and imaging outcome measures which will be secondary outcome measures completed at baseline and intermittently throughout the study. The duration of the study is one year.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23224
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Early/Mild to Moderate Stage knee osteoarthritis (KOA), as determined by Kellgren-Lawrence Grade 2 to 3 on PA standing radiograph within the past three months;

   • A prospective subject who has a diagnosis of non-end stage KOA (i.e., a potential study candidate) and expresses interest in participating but has no XRAY within the specified time-period will be sent for a fresh XRAY. This XRAY will be read by a radiologist & be paid for by the study.
2. >=40 years of age;

3. Average 100-point VAS score of >50, on average, within the past 3 months*, with KOA felt to be the primary contributor to pain.

   • Alternate 10-point scales with pain scores averaging >5 may be considered if the prospective subject also completes a VAS with score >50 at screening.
4. Exam consistent with KOA being primary etiology of pain;
5. No signs of inflammatory arthropathy in medical record, history or physical examination;
6. A >3 millimeter intra-articular (IA) effusion present on ultrasound evaluation.
7. [If a chronic liver or renal disease patient, evidence of stable disease over/within the past six months, else exclusion.]
8. Veteran receiving care at McGuire VAMC.

Exclusion Criteria:

1. Morbid obesity (BMI >40);
2. Poorly controlled diabetes (hemoglobin A1C > 7.5 or fasting blood glucose of >200) in last 6 months;
3. Ipsilateral knee surgery, trauma within last 6 months, or corticosteroid injection within 3 months.
4. 4. History of inflammatory arthropathy (RA, SLE or crystalline arthritis of the knee)**;
5. Any rheumatoid arthritis or gout diagnosis is exclusionary.
6. Current infection of the affected joint or any other uncontrolled or untreated active infection.

7. Moderate to severe anemia (hemoglobin < 11 g/dl) or thrombocytopenia (platelet count < 100,000); Hemoglobin >17 g/dl or <11 g/dl and/or platelet counts >500,000 or <100,000 platelets/μl.

   • [CBC obtained within 6 months will be required, even if obtained at initial screening visit.]

8. Individuals on dialysis, with liver failure, or uncontrolled renal or liver disease are excluded.

   • In those with chronic renal or liver disease, documentation of stable disease within the most recent 6 months will be required.

9. Individuals on a therapeutic anticoagulant (e.g., Warfarin, Dabigatran, Enoxaparin) and those with a history of coagulopathy are excluded.

   • Per standard clinical practice, subjects on anti-platelet therapy are not excluded.

10. Pregnancy or breast-feeding;

    • Female subjects of child-bearing potential must have a negative pregnancy screen prior to enrollment.
    • Female subjects of child-bearing potential must confirm they are not actively breast-feeding prior to enrollment.
11. Current illicit drug abuse / active alcohol abuse (i.e, Current substance abuse);
12. Uncontrolled psychiatric disorder;
13. Lack of transportation (i.e., to get to/from appointments at VAMC) and/or willingness to attend study appointments (screening/consent, Intervention, Day10-follow-up, Month-6 follow-up, and then visits over-the-phone / in-person / or via Telehealth for Month-3 and Month-12;
14. Advanced or currently active cancer.
15. Blood disorders (such as Sickle Cell Anemia, TTP, others)
16. Vulnerable populations: Individuals incapable of making informed decisions will not be enrolled, nor will those under some form of incarceration.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Platelet Rich Plasma; Approximately 5mL of intraarticular PRP once at baseline	Biological: Platelet Rich Plasma; Platelet rich plasma injection into knee versus placebo (saline) injection.; Other Names: Platelet Concentrate
Other: Normal Saline; Approximately 5mL of intraarticular normal saline once at baseline	Other: Normal Saline; Platelet rich plasma injection into knee versus placebo (saline) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biochemical Molecular Outcomes	Evaluate for change in biochemical molecular milieu temporal response after PRP injection or normal saline (control) compared to baseline, as measured by multiplex suspension array technology.	Baseline and 10 day follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcomes	Evaluation for change in pain level via VAS and WOMAC at baseline and follow up.	1 year
Imaging Outcomes	Evaluation for change in joint space width using knee radiographs at baseline and 6 month follow up.	6 months

Collaborators and Investigators

• Sponsor: Hunter Holmes Mcguire Veteran Affairs Medical Center
• Collaborators: Foundation for Physical Medicine and Rehabilitation
• Investigators: Principal Investigator: Lance L Goetz, MD, Hunter Holmes McGuire VAMC

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 31, 2015
• First Submitted That Met QC Criteria: June 9, 2015
• First Posted (Estimate): June 10, 2015

Study Record Updates

• Last Update Posted (Actual): August 16, 2017
• Last Update Submitted That Met QC Criteria: August 13, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Stem Cells; Knee Osteoarthritis; Platelet Rich Plasma; Synovial Fluid; Mechanism of Action
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: IRB #01979/FDA IDE#15944

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Publications planned.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes