Investigation of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee

• ClinicalTrials.gov Identifier: NCT02958267
• Recruitment Status: Completed
• First Posted: November 8, 2016
• Results First Posted: September 24, 2019
• Last Update Posted: September 24, 2019
• Sponsor: OhioHealth
• Information provided by (Responsible Party): Joseph Ruane, OhioHealth

Study Description

Brief Summary:

The purpose of this study is to determine the clinical response to autologous bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) injections for knee osteoarthritis with respect to pain, function, and quality of life at up to 1 year following the intervention. Specifically, the clinical response will be compared to baseline and a control group treated with a Gel-One® hyaluronate injection to the target knee.

Condition or disease	Intervention/treatment	Phase
Knee Osteoarthritis	Biological: BMAC injection; Biological: PRP injection; Device: Gel-One® hyaluronate injection	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Investigation of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee: Effect on Pain and Quality of Life
• Study Start Date: December 2016
• Actual Primary Completion Date: August 2018
• Actual Study Completion Date: August 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: BMAC injection and PRP injection; Injection of bone marrow aspirate concentrate (BMAC) withdrawn from a bone near the hip into the knee joint (intra-articular) immediately followed by an injection of platelet-rich plasma (PRP) into the knee joint.	Biological: BMAC injection; 60mL of bone marrow will be collected from a bone near the hip. Approximately 5-6mL of the bone marrow aspirate concentrate is then used for injection, under ultrasound guidance, into the target knee by the study physician.; Biological: PRP injection; 60mL of venous blood will be withdrawn from either arm. Approximately 4-5 ml of platelet-rich plasma will be introduced under ultrasound guidance to the subject's target knee by the study physician.
Active Comparator: Gel-One® hyaluronate injection; Gel-One® is an hyaluronate gel used in the treatment of knee osteoarthritis by injection into the knee joint (intra-articular).	Device: Gel-One® hyaluronate injection; Patients will receive a single injection of Gel-One® (3 ml syringe of Gel-One® - 1% solution [10 mg/mL], 30mg total hyaluronan) into the target knee. Injections will be performed by the study physician under real-time dynamic ultrasound guidance.

Outcome Measures

Primary Outcome Measures :

1. Knee Injury and Osteoarthritis Outcome Score [ Time Frame: Change from baseline to 3, 6, and 12 months post-treatment ]
   Subscales include pain, symptoms, function in activities of daily living, function in sport and recreation, and knee-related quality of life. Each subscale is 0-100 with 100 indicating the best possible score.

Secondary Outcome Measures :

1. Numeric Pain Rating Scale [ Time Frame: Change from baseline to 3, 6, and 12 months post-treatment ]
   Scale from 0-10 with 0 representing "no pain" and 10 representing "worst imaginable pain"
2. Patient Reported Outcome Measurement Information System Global Health Scores [ Time Frame: Change from baseline to 3, 6, and 12 months post-treatment ]
   The Patient Reported Outcomes Measurement Information System (PROMIS®) Global Health scale v1.1 contains 10 questions and produces two subscale scores: Global Physical Health (GPH) and Global Mental Health (GMH) (Hays, Bjorner, Revicki, Spritzer, & Cella, 2009). Each subscale produces a raw score that is converted to a T score such that an average patient in the United States would have a subscale T score of 50 with a standard deviation of 10 points ("Global Health: A Brief Guide to the PROMIS® Global Health Instruments", 2017). A score higher than the mean indicates a more desirable score, and vice versa. A positive change score indicates an improvement, while a negative change score indicates a decline in score value.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male and female patients 40 to 70 years old
2. Diagnosed with knee osteoarthritis based on the American College of Rheumatology criteria including symptomatic reports and radiographic findings
3. Kellgren-Lawrence grade 1-3 based on a radiograph within 6 months of presentation to the clinic
4. Symptomatic evidence of tibiofemoral osteoarthritis for ≥6 months
5. Average numeric pain rating of 4 - 8 on a scale of zero to 10 (defined as moderate level) over the past week
6. Previous trial of 6 weeks minimum of conservative therapy including physical therapy, weight loss, anti-inflammatory medication, or injection therapy

Exclusion Criteria:

1. Grade 4 knee osteoarthritis according to the Kellgren-Lawrence scale
2. History of intraarticular viscosupplementation or steroid injection in the target knee in the past 6 months at the time of the baseline visit or intraarticular injection planned during the trial
3. History of arthroscopic surgery in the target knee in the past 12 months at the time of presentation to the clinic or planned surgery during the trial period (e.g., scheduled for/awaiting arthroscopy or a knee replacement procedure)
4. Bilateral knee osteoarthritis (unless the contralateral knee involvement is limited to radiographic osteoarthritis and not symptomatic)
5. Ipsilateral (same side) or contralateral (opposite side) symptomatic osteoarthritis of hip or ankle
6. Clinically apparent tense effusion or other acute inflammation of the target knee at the time of presentation to the clinic
7. Active infection of either lower extremity such as cellulitis or any skin disease or infection in the area where BMAC is aspirated, blood is drawn, or an injection is given
8. History of diagnosis of any of the following: 1) septic osteoarthritis of any joint, 2) inflammatory arthropathy such as rheumatoid arthritis, gout, pseudogout, lupus, crystalline arthropathy, chondrocalcinosis and other rheumatology diagnoses
9. Cruciate/collateral knee ligament instability, ligament laxity, or meniscal instability of the target knee
10. Significant alignment deformity such as varus/valgus of the target knee in the judgment of the investigator
11. Currently pregnant, nursing, or planning to become pregnant during the trial period
12. Previous or known allergic reaction or hypersensitivity to heparin; sodium citrate; hyaluronan products or specifically Gel-One®; cinnamon; bird products such as feathers, eggs, or poultry; avian proteins
13. Not suitable for BMAC tissue allograft injection per physician (e.g., blood dyscrasia)
14. Unable to be prescribed stable dose of NSAIDs and/or tramadol based on medical history as ad lib use of over-the-counter analgesics will be allowed in both groups after treatment
15. Current cigarette smoker
16. Unable to give informed consent
17. Non-English speaking

Contacts and Locations

Locations

United States, Ohio

McConnell Spine, Sport, and Joint Physicians

Columbus, Ohio, United States, 43214

Sponsors and Collaborators

OhioHealth

Investigators

• Principal Investigator: Joseph J Ruane, DO; Medical Director, McConnell Heart Health Center

  Study Documents (Full-Text)

Documents provided by Joseph Ruane, OhioHealth:

Study Protocol and Statistical Analysis Plan  [PDF] March 28, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ruane JJ, Ross A, Zigmont V, McClure D, Gascon G. A Single-Blinded Randomized Controlled Trial of Mesenchymal Stem Cell Therapy for the Treatment of Osteoarthritis of the Knee with Active Control. J Stem Cells Regen Med. 2021 Jan 2;17(1):3-17. doi: 10.46582/jsrm.1701002. eCollection 2021.

• Responsible Party: Joseph Ruane, Principal Investigator - Medical Director, McConnell Heart Health Center, OhioHealth
• ClinicalTrials.gov Identifier: NCT02958267
• Other Study ID Numbers: OH1-16-00672
• First Posted: November 8, 2016
• Results First Posted: September 24, 2019
• Last Update Posted: September 24, 2019
• Last Verified: September 2019

Keywords provided by Joseph Ruane, OhioHealth:

knee osteoarthritis; regenerative medicine; orthobiologics; cellular therapy

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Hyaluronic Acid; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Viscosupplements; Protective Agents