Autologous BMA vs Saline and LAM + LP-PRP vs Saline Evaluations in Knee OA
ConditionOsteoarthritis, Knee
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age30+
SponsorUniversity Health Network, Toronto
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Bone Marrow Aspirate (BMA): Minimally manipulated autologous cellular preparation
Biological/VaccineParticipants 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).
Saline (Placebo Comparator for BMA)
Other interventionParticipants 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).
Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP): Minimally manipulated autologous cellular preparations
Biological/VaccineParticipants 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).
Saline (Placebo Comparator for LAM + LP-PRP)
Other interventionParticipants 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).
Treatment groups
148 Participants
are divided into 4 treatment groupsGroup A: For STUDY 1 (ARM A): Bone Marrow Aspirate (BMA)Experimental treatment 1 intervention
Group B: For STUDY 1 (ARM C): Saline InjectionPlacebo comparator 1 intervention
Group C: For STUDY 2 (ARM B): Lipoaspirate Micronized + Leukocyte-Poor Platelet-Rich Plasma (LAM + LP-PRP)Experimental treatment 1 intervention
Group D: For STUDY 2 (ARM D): Saline InjectionPlacebo comparator 1 intervention
Trial outcomes
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".
Time frame
baseline (pre-injection) and 3, 6 and 12 months (post-injection)Secondary outcomes
1
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.
KOOS was originally developed in 1995 by Ewa M Roos and colleagues. The KOOS was developed as an extension of the WOMAC Osteoarthritis Index with the purpose of evaluating short- and long-term symptoms and function in subjects with knee injury and OA. It holds 42 items in 5 separately scored subscales: Pain, other Symptoms, Function in Daily Living (ADL), Function in Sport and Recreation (Sport/Rec), and knee-related Quality of Life (QOL). Standardized answer options are given (5 Likert boxes) and each question is assigned a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.
Time frame
baseline (pre-injection) and 3, 6 and 12 months (post-injection)2
Additional Pain Level Changes. Mean NPRS subscale change score at 6 months relative to baseline in treatment groups compared to placebo groups.
See above for description of NPRS.
Time frame
baseline (pre-injection) and 3, 6 and 12 months (post-injection)3
Additional Pain Level Changes. Mean KOOS pain subscale change score at 6 months relative to baseline in treatment groups compared to placebo groups.
See above for description of KOOS.
Time frame
baseline (pre-injection) and 3, 6 and 12 months (post-injection)4
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.
EQ-5D-5L is a commonly used generic preference-based health-related QOL measure. It is a multi-attribute instrument, which considers five dimensions including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Respondents are asked to rate their health today on each dimension. Each dimension has five levels of severity i.e., no problems (level 1); slight; moderate; severe; and extreme problems (level 5). There are 3,125 possible health states defined by combining one level from each dimension, ranging from 11111 (full health) to 55555 (worst health). The health states are converted into a single index 'utility' score using a scoring algorithm. There is also a VAS, which is used as a quantitative measure of overall health status i.e., 0 represents the worst health you can imagine and 100 represents the best health you can imagine.
Time frame
baseline (pre-injection) and 3, 6 and 12 months (post-injection)Other outcomes
1
Total nucleated cell count (TNC) in the BMA and LAM cellular preparations in treatment groups only.
This is to address heterogeneity in the cellular composition of cellular autologous preparations. The correlation between TNC and NPRS/KOOS pain and KOOS ADL scores at 6 months relative to baseline will be evaluated.
Time frame
baseline (pre-injection) and 6 months (post-injection)2
Percentages of hematopoietic, endothelial, and stromal cells in the BMA and LAM cellular preparations in treatment groups only.
This is to address heterogeneity in the cellular composition of cellular autologous preparations. The correlation between the sub-population fractions and NPRS/KOOS pain and KOOS ADL scores at 6 months relative to baseline will be evaluated.
Time frame
baseline (pre-injection) and 6 months (post-injection)3
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.
This is to address heterogeneity in the cellular composition of cellular autologous preparations. The correlation between soluble/secreted factor levels and NPRS/KOOS pain and KOOS ADL scores at 6 months relative to baseline will be evaluated.
Time frame
baseline (pre-injection) and 6 months (post-injection)4
Local and systemic levels of immune cells and inflammatory cytokines and chemokines in synovial fluid and blood in treatment groups and placebo groups.
This is to address heterogeneity in the inflammatory/immune cell profiles of patients and evaluate correlation to NPRS/KOOS pain and KOOS ADL scores at 6 months relative to baseline.
Time frame
baseline (pre-injection) and 6 months (post-injection)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University Health Network, Toronto
Lead sponsor
Women's College Hospital
Collaborator
Source ClinicalTrials.gov