Effectiveness of PRP, Conditioned Medium UC-MSCs Secretome and Hyaluronic Acid for the Treatment of Knee Osteoarthritis

Study Overview
=================
Brief Summary
-----------------
The clinical trial will be carried out at the Dr. Moh. Hoesin Central Hospital, Palembang and planned from October 2022 to March 2023. This study aims to compare the efficacy of Platelet Rich Plasma, Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell (MSC) Culture Secretome and hyaluronic acid for the Treatment of Knee Osteoarthritis

Detailed Description
-----------------
In this, prospective, Open-label study, patients with mild to moderate symptomatic knee osteoarthritis will be randomized to receive either a series of platelet-rich plasma or hyaluronic acid or Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell (MSC) Culture Secretome injections under ultrasound guidance. Each of the groups were given 5 times injection 3 cc platelet-rich plasma or 2 cc hyaluronic acid or 2cc Conditioned Medium From Umbilical Cord MSC Secretome at intervals 1 weeks. Clinical data in the form of subjective outcome measures will be collected pre-treatment and 6 months after injection.

Official Title
-----------------
Comparative Effectiveness of Platelet Rich Plasma (PRP), Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome and Hyaluronic Acid (HA) for the Treatment of Knee Osteoarthritis

Conditions
-----------------
Knee Osteoarthritis

Intervention / Treatment
-----------------
* Biological: Platelet-rich Plasma
* Biological: Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome
* Drug: Low Molecular Weight Hyaluronic Acid


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients aged 30-60 years Suffering from grade 2 and 3 osteoarthritis (OA) was identified by two observers who differed accordingly the Kellgren and Lawrence research scale Patient with knee pain that had been continuing for at least 12 months with no relief using anti-inﬂammatory medications and that deteriorated with weight-bearing Patients can understand the nature of the study and written informed consent is given to patients Exclusion Criteria: Age > 60 years Acute Knee Osteoarthritis Effusions Patients are not willing to obey the study protocol There are signs of infection local or general infection or positive serology for HIV, hepatitis and syphilis There is a congenital disease that causes significant deformity of the knee can interfere with cell applications and interpret results Articular injection of the knee by any drug during the previous 3 months Participate in any clinical trial or treatment 30 days before the study Other conditions may, according to medical criteria, not support participation in this research (The recent history of knee trauma, Autoimmune rheumatic diseases, Uncontrolled systemic diseases such as diabetes or hypertension, patient with Immunosuppressive or anticoagulant treatment and cancer)

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Platelet-rich Plasma (PRP)<br>Platelet-rich plasma administered 5 times as an intra-articular injection under ultrasound guidance as a series of one weekly injections to the affected knee. 1 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 3mL in volume. | Biological: Platelet-rich Plasma<br>* Research participants own blood will be used to prepare the platelet rich plasma injectate.<br>* Other names: PRP;|
| Experimental: Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome<br>Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome administered 5 times as an intra-articular injection under ultrasound guidance as a series of one weekly injections to the affected knee. 1 weekly injections are Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome averaging 2 mL in volume. | Biological: Conditioned Medium From Umbilical Cord Mesenchymal Stem Cell Culture (MSCs) Secretome<br>* Conditioned Medium UC-MSCs Secretome which will be injected into the affected knee using ultrasound guidance.<br>* Other names: Conditioned Medium UC-MSCs Secretome;|
| Experimental: Hyaluronic Acid (HA)<br>Hyaluronic Acid administered 5 times as an intra-articular injection under ultrasound guidance as a series of one weekly injections to the affected knee. 1 weekly injections are of low molecular weight hyaluronan in a 2mL injection. | Drug: Low Molecular Weight Hyaluronic Acid<br>* low molecular weight hyaluronic acid which will be injected into the affected knee using ultrasound guidance.<br>* Other names: HA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale (VAS) | To asses pain score, score 1(good)-10(worst) | Pre-Treatment | 
| Visual Analog Scale (VAS) | To asses pain score, score 1(good)-10(worst) | 3 month after injection | 
| Visual Analog Scale (VAS) | To asses pain score, score 1(good)-10(worst) | 6 month after injection | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | To evaluate the condition of patients with osteoarthritis, including pain, stiffness, and physical functioning of the joints. The WOMAC is a self administered questionnaire consisting of 24 items divided into subscales including pain (0-20), stiffness (0-8) and physical function (0-68). Higher scores indicate worse pain, stiffness and functional limitations. | Pre-Treatment | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | To evaluate the condition of patients with osteoarthritis, including pain, stiffness, and physical functioning of the joints. The WOMAC is a self administered questionnaire consisting of 24 items divided into subscales including pain (0-20), stiffness (0-8) and physical function (0-68). Higher scores indicate worse pain, stiffness and functional limitations. | 3 month after injection | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) | To evaluate the condition of patients with osteoarthritis, including pain, stiffness, and physical functioning of the joints. The WOMAC is a self administered questionnaire consisting of 24 items divided into subscales including pain (0-20), stiffness (0-8) and physical function (0-68). Higher scores indicate worse pain, stiffness and functional limitations. | 6 month after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory Assessment | Cartilage Oligomeric Matrix Protein (COMP) | Pre-Treatment | 
| Laboratory Assessment | Cartilage Oligomeric Matrix Protein (COMP) | 3 month after injection |