Autologous BMA vs Saline and LAM + LP-PRP vs Saline Evaluations in Knee OA

NCT05517434 | Recruiting Phase 2 DMC

• 2 other identifiers: 22-595922-5792 (ABLE OA, study 2)
• Study Type: interventional
• Target: 148
• Locations: 1 country
• Sites: 2

Brief Summary

ABLE OA is a Health Canada authorized (phase II/III) trial \[Parent Control #: 263591\]. A multi-center, prospective, double-blinded, randomized, placebo-controlled adaptive trial to evaluate the efficacy of two minimally manipulated autologous cellular preparations i) bone marrow aspirate (BMA) injection; and, ii) combined lipoaspirate micronized (LAM) and leukocyte poor (LP) platelet-rich plasma (PRP) injections for the treatment of knee osteoarthritis (OA). BMA, LAM from lipoaspirate (LA), and LP-PRP from whole blood will be prepared using the Cervos Marrow Cellution™ Bone Marrow Aspiration System, Cervos LIPO-PRO™ Adipose Transfer System, and Cervos KEYPRP Platelet Separator System, respectively. Patient-reported outcome (PRO) measures will be collected using web- or paper-based questionnaires administered at baseline (pre-injection) as well as at 3, 6 and 12 months (post-injection). Blood, synovial fluid, and urine samples will be collected at baseline pre-injection and 6 months post-injection only.

Conditions

Osteoarthritis, Knee

Keywords

placebo; intra-articular injection; autologous therapy; bone marrow aspirate; lipoaspirate; platelet-rich plasma; leukocyte-poor; pain

Outcome Measures

Primary Outcomes (1)

• Pain Level Changes. Differences in response rates between groups (treatments vs placebos) at 6-months (end of study) compared to baseline. Response is based on an improvement of 2 units or more in the Numeric Pain Rating Scale (NPRS).

  Pain intensity will be measured by the NPRS. The score ranges from 0 to 10, with 0 indicating "No Pain" and 10 "Worst Imaginable Pain".

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

Secondary Outcomes (6)

• Functional Changes. Differences in mean change of Knee Injury and Osteoarthritis Outcome Score (KOOS) Activities of Daily Living (ADL) subscale scores between groups (treatments vs placebos) at 6-months (end of study) compared to baseline.

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

• Additional Pain Level Changes. Mean NPRS subscale change score at 6 months relative to baseline in treatment groups compared to placebo groups.

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

• Additional Pain Level Changes. Mean KOOS pain subscale change score at 6 months relative to baseline in treatment groups compared to placebo groups.

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

• Health-Related Quality of Life Changes. Mean utility and EuroQol-Visual Analogue Scale (EQ-VAS) change scores at 6 months (end of study) relative to baseline in treatment groups compared to placebo groups.

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

• Safety. Proportion of cumulative adverse events (AEs) at 6 months post-injection in treatment groups compared to placebo groups.

  baseline (pre-injection) and 3, 6 and 12 months (post-injection)

Other Outcomes (5)

• Total nucleated cell count (TNC) in the BMA and LAM cellular preparations in treatment groups only.

  baseline (pre-injection) and 6 months (post-injection)

• Percentages of hematopoietic, endothelial, and stromal cells in the BMA and LAM cellular preparations in treatment groups only.

  baseline (pre-injection) and 6 months (post-injection)

• Levels of soluble/secreted factors (FGF2, G-CSF, IL-1RA/IL-1F3, IL-4, IL-10, PDGF-BB, VEGF) in the BMA, LAM and LP-PRP cellular preparations in treatment groups only.

  baseline (pre-injection) and 6 months (post-injection)

Study Arms (4)

For STUDY 1 (ARM A): Bone Marrow Aspirate (BMA)

EXPERIMENTAL

This group will undergo a bone marrow aspiration and receive an ultrasound guided intra-articular injection of BMA (a single dose of cellular suspension of 9 mL or less)

Biological: Bone Marrow Aspirate (BMA): Minimally manipulated autologous cellular preparation

For STUDY 1 (ARM C): Saline Injection

PLACEBO COMPARATOR

This group will undergo a bone marrow aspiration and receive an ultrasound guided intra-articular injection of saline solution (9 mL)

Other: Saline (Placebo Comparator for BMA)

For STUDY 2 (ARM B): Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP)

EXPERIMENTAL

This group will undergo a blood collection plus lipoaspiration and receive an ultrasound guided intra-articular injection of LAM (a single dose of cellular suspension of 9 mL or less) followed by LP-PRP (a single dose of cellular suspension of 2 mL or less)

Biological: Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP): Minimally manipulated autologous cellular preparations

For STUDY 2 (ARM D): Saline Injection

PLACEBO COMPARATOR

This group will undergo a blood collection plus lipoaspiration and receive ultrasound guided intra-articular injections of saline solution (9 mL followed by 2 mL)

Other: Saline (Placebo Comparator for LAM + LP-PRP)

Interventions

Saline (Placebo Comparator for BMA) OTHER

Participants will undergo a bone marrow aspiration to collect about 10 mL of BMA from the posterior iliac spine i.e., ipsilateral and/or contralateral iliac crest. However, 0.9% sodium chloride (NaCl) Baxter or equivalent (9 mL) is injected into the osteoarthritic knee joint (Arm C, Study 1).

For STUDY 1 (ARM C): Saline Injection

Saline (Placebo Comparator for LAM + LP-PRP) OTHER

Participants will undergo a lipoaspiration to collect 40 mL of LA and a blood draw to collect about 30 mL of whole blood. However, 0.9% of sodium chloride (NaCl) Baxter or equivalent is injected twice (9 mL + 2 mL) into the osteoarthritic knee joint (Arm D, Study 2).

For STUDY 2 (ARM D): Saline Injection

Bone Marrow Aspirate (BMA): Minimally manipulated autologous cellular preparation BIOLOGICAL

Participants will undergo a bone marrow aspiration. About 10 mL of BMA will be collected from the posterior iliac spine i.e., ipsilateral and/or contralateral iliac crest using the Cervos Marrow Cellution™ kit. The BMA does not require processing using a centrifuge after collection. 9 mL (or less) of BMA is injected into the osteoarthritic knee joint after collection (Arm A, Study 1).

For STUDY 1 (ARM A): Bone Marrow Aspirate (BMA)

Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP): Minimally manipulated autologous cellular preparations BIOLOGICAL

Participants will undergo a lipoaspiration. 40 mL of lipoaspirate (LA) will be collected from subcutaneous adipose tissue. LA will be processed using the Cervos LIPO-PRO™ kit and a centrifuge. Participants will also undergo a blood draw. About 30 mL of whole blood will be collected from the antecubital fossa. Whole blood will be processed using the Cervos KEYPRP kit and a centrifuge. After processing, 9 mL (or less) of LAM is injected first followed immediately by 2 mL (or less) of LP-PRP into the osteoarthritic knee joint (Arm B, Study 2).

For STUDY 2 (ARM B): Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP)

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female at least 30 years of age at the time of screening
• Willingness and ability to comply with study procedures and visit schedules and able to follow oral and written instructions
• Signed consent for study participation
• Baseline NPRS ≥ 4 points
• Presence of chronic, symptomatic knee pain in at least one knee; if both knees are affected, the knee with greater severity will be selected for treatment
• KL grade 2 or 3 knee OA based on standing knee X-ray assessment
• Body mass index ≤ 30 kg/m2

You may not qualify if:

• Approved anti-inflammatory therapy injections (corticosteroid, Synvisc, PRP, nSTRIDE-Autologous Protein Solution) within the previous 6 months in the knee
• Major axial deviation (varus \>10°, valgus \>10°)
• Any concomitant knee lesion causing pain or effusion (i.e., ligamentous or meniscal injury, osteochondral lesion)
• Presence of clinically observed active infection in the index knee
• Diagnosed with rheumatoid arthritis, Reiter's syndrome, psoriatic arthritis, gout, ankylosing spondylitis, or arthritis secondary to other inflammatory diseases; chondrocalcinosis, Paget's disease, or villonodular synovitis
• Diagnosed with leukemia or other hematologic cancers, known presence of metastatic malignant cells, or ongoing or planned chemotherapeutic treatment
• Presence of venous or lymphatic stasis in the index leg
• A history of local anesthetic allergy
• Medical conditions such as hemophilia or other blood clotting disorders
• Arthroscopic knee surgery within the previous 6 months
• Daily opioid use for the past 3 months, use of non-steroidal anti-inflammatory drugs within 1 week of the procedure, unable to hold anti-platelet medications
• Use of systemic corticosteroids for treatment of a chronic medical condition within the past 3 months
• Immunosuppression or acute infective processes
• For Study 1: Inability to tolerate the bone marrow aspiration procedure resulting in insufficient collection of BMA (\<10 mL) after two successive aspiration attempts
• For Study 2: Inability to tolerate the lipoaspiration procedure resulting in insufficient collection of LA (\<40 mL) after two successive aspiration attempts

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Women's College Hospital: collaborator

Study Sites (2)

Women's College Hospital

Toronto, Ontario, M5S 1B2, Canada

NOT YET RECRUITING

Toronto Western Hospital, University Health Network

Toronto, Ontario, M5T 2S8, Canada

RECRUITING

MeSH Terms

Conditions

Osteoarthritis, Knee; Pain

Interventions

Sodium Chloride; cyclomaltodextrin glucanotransferase; lipoarabinomannan

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Sowmya Viswanathan, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Christian Veillette, MD, MSc, FRCSC

  University Health Network, Toronto

  STUDY DIRECTOR

• Christopher Kim, HBSc, MSc, MD, FRCSC, PhD(c)

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shoba Singh

CONTACT

416-634-7240; Shoba.Singh@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A research nurse/staff will prepare the minimally manipulated cellular preparations and injection syringe(s), as well as deliver the corresponding syringe(s) based on group allocation to the clinician to administer the injection into the patient's knee joint. The syringe(s) containing the active treatment or saline solution will be obscured by a non-transparent, adhesive label hiding its content in order to maintain the blind for both the patient and clinician.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: STUDY 1 (N=74): All patients will undergo a bone marrow aspiration. A BMA injection \[Arm A, n=37\] will be compared to a saline injection \[Arm C, n=37\]. STUDY 2 (N=74): All patients will undergo a blood collection and lipoaspiration. A LAM injection followed by LP-PRP injection \[Arm B, n=37\] will be compared to two consecutive saline injections \[Arm D, n=37\].

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: August 26, 2022
• Study Start: January 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)