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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Knee Osteoarthristis
• Intervention / Treatment: Biological: Human amniotic suspension allograft (ASA)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kuan-Yu Lin; Phone Number: 3051 +886-7-3422121; Email: johnkyl@yahoo.com
• Study Contact Backup: Name: Yin-Ming Huang; Phone Number: 3051 +886-7-3422121; Email: rex781104@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human amniotic suspension allograft (ASA), 40 mg; 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); Human amniotic suspension allograft (ASA) intra-articular injection.
Experimental: Human amniotic suspension allograft (ASA), 20 mg; 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); Human amniotic suspension allograft (ASA) intra-articular injection.
Experimental: CellularMatrix (a combination of platelet-rich plasma and hyaluronic acid); 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); Human amniotic suspension allograft (ASA) intra-articular injection.
Placebo Comparator: Normal saline; 4ml of normal saline	Biological: Human amniotic suspension allograft (ASA); Human amniotic suspension allograft (ASA) intra-articular injection.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kaohsiung Veterans General Hospital.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2021
• Primary Completion (Anticipated): January 31, 2022
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: January 5, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): January 6, 2021
• Last Update Submitted That Met QC Criteria: January 5, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: KSVGH20-CT9-11, ASA RCT 1.0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We do not have the plan to make individual participant data (IPD) available to other researchers.

Drug and device information, study documents

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