Efficacy of Intra-articular Injection of Human Amniotic Suspension Allograft and Platelet-rich Plasma in the Treatment of Knee Osteoarthritis.

Study Overview
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Brief Summary
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A double-blind, randomized controlled trial designed to evaluate the symptomatic modulating efficacy of amniotic suspension allograft (ASA) in comparison to platelet-rich plasma (PRP), hyaluronic acid (HA) and normal saline (NS) in the injection treatment of knee osteoarthritis. The hypothesis is that ASA would provide the greatest functional improvement.

Detailed Description
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At least 150 subjects with osteoarthritic knee will be recruited and computer randomized 1:1:1:1 to single injection of ASA (40mg), ASA (20mg), PRP + HA, and NS groups. Both subjects and evaluaters were blinded to allocations. Functional and radiologic outcomes were measured at baseline, and 1 week, 1, 3, 6, 12 months postinjection.

Official Title
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Comparison of the Efficacy of Intra-articular Injection of Human Amniotic Suspension Allograft and Platelet-rich Plasma in the Treatment of Knee Osteoarthritis: A Prospective, Double-blind, Randomized Controlled Trial

Conditions
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Knee Osteoarthristis

Intervention / Treatment
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* Biological: Human amniotic suspension allograft (ASA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20 and 80 years Ability to provide informed consent Unilateral or bilateral knee VAS pain score ≥ 4 of 10 (worst possible pain) for more than 4 months Diagnosis of OA Kellgren-Lawrence I-III by radiography (triple-film of bilateral lower limb, standard knee anterior-posterior view in full extension, lateral view in 30-degrees flexion, and 45°Merchant views) No prior PRP injection of knee No prior surgical procedure of the participating knee BMI<40 kg/m2 Exclusion Criteria: Lawrence stage IV Major axial deviation (varus> 5°, valgus > 5°) Any concomitant symptomatic knee disorder (i.e. ligamentous/ meniscal injury) Systemic inflammatory arthropathy Hematologic diseases Severe cardiovascular disease Neurological disorders Active infection Immuno-compromised Therapy with anticoagulants or antiaggregants Use of NSAIDs and/or chondroprotective supplements, such as glucosamines and chondroitin sulfates, within 7 days prior to trial Recent intra-articular injection of corticosteroids (within 30 days) Prior treatment with HA in past 6 monthsHb< 11 g/dL Platelet count < 150,000/mm3

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human amniotic suspension allograft (ASA), 40 mg<br>Human amniotic suspension allograft (ASA) contains particulated human amniotic membrane and cells derived from the amniotic fluid. The allograft is freeze-dried, terminally sterilized with low dose gamma irradiation. Arm 1 uses 40 mg ASA stored in a sterile vial (Amniogen, HTC Regenerative Ltd. New Taipei, Taiwan). | Biological: Human amniotic suspension allograft (ASA)<br>* Human amniotic suspension allograft (ASA) intra-articular injection.<br>|
| Experimental: Human amniotic suspension allograft (ASA), 20 mg<br>Human amniotic suspension allograft (ASA) contains particulated human amniotic membrane and cells derived from the amniotic fluid. The allograft is freeze-dried, terminally sterilized with low dose gamma irradiation. Arm 2 uses 20 mg ASA stored in a sterile vial (Amniogen, HTC Regenerative Ltd. New Taipei, Taiwan). | Biological: Human amniotic suspension allograft (ASA)<br>* Human amniotic suspension allograft (ASA) intra-articular injection.<br>|
| Experimental: CellularMatrix (a combination of platelet-rich plasma and hyaluronic acid)<br>CellularMatrix (RegenLab SA, Switzerland) is composed of sterile and non-pyrogenic tubes allowing the mix of Platelet Rich Plasma (PRP) with Hyaluronic Acid (HA) in the same proportion (2mL of PRP for 2mL of HA). | Biological: Human amniotic suspension allograft (ASA)<br>* Human amniotic suspension allograft (ASA) intra-articular injection.<br>|
| Placebo Comparator: Normal saline<br>4ml of normal saline | Biological: Human amniotic suspension allograft (ASA)<br>* Human amniotic suspension allograft (ASA) intra-articular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the Western Ontario and McMaster Universities Arthritis Index (WOMAC) between baseline, 1 week, and 1 ,3 ,6 ,12 months. | WOMAC is a self-administered questionnaire consisting of 24 items divided into 3 subscales:(1) Pain (5 items): during walking, using stairs, in bed, sitting or lying, and standing upright(2) Stiffness (2 items): after first waking and later in the day(3) Physical Function (17 items): using stairs, rising from sitting, standing, bending, walking, getting in / out of a car, shopping, putting on / taking off socks, rising from bed, lying in bed, getting in / out of bath, sitting, getting on / off toilet, heavy domestic duties, light domestic dutiesThe test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). | Baseline, 1 week, 1,3,6,12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the International Knee Documentation Committee (IKDC Questionnaire) between baseline, 1 week, and 1 ,3 ,6 ,12 months. | The International Knee Documentation Committee Questionnaire is a knee-specific patient-reported outcome measure.The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things such as pain, stiffness, swelling and giving-way of the knee. Meanwhile, the sports activity subscale focuses on functions like going up and down the stairs, rising from a chair, squatting and jumping. The knee function subscale asks patients one simple question: how is their knee at present versus how was their knee prior to injury? Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100, This final number is interpreted as a measure of function with higher scores representing higher levels of function. | Baseline, 1 week, 1,3,6,12 months |