Prolotherapy Intervention Effect in Patient With Knee Osteoarthritis

Phase 4

Completed

• Conditions: Knee Osteoarthritis
• Interventions: Drug: Prolotherapy; Drug: Sodium Hyaluronate

• Registration Number: NCT04557943
• Lead Sponsor: Hasanuddin University

Brief Summary

Introduction :

Prolotherapy is regenerative tissue therapy which is considered to be efficacious in reducing symptoms and morbidity of Knee Osteoarthritis (KOA), but only a few studies demonstrate the effect of prolotherapy at the biomolecular level, particularly the level of Cartilage Oligomeric Matrix Protein (COMP), and Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II) as the biomarkers of cartilage repair.

Objective:

To determine the effect of prolotherapy on COMP and uCTX-II levels, and functional outcomes in KOA patients.

Method:

a double-blind randomized controlled trial study involving 36 participants who had been diagnosed with KOA. History taking, functional outcome assessment, COMP, and uCTX-II were measured. The prolotherapy via intraarticular and extraarticular was performed at Day-1, Day-29, and Day-57 followed by the evaluation of functional outcome, COMP, and uCTX-II at day 78

Alternative Hypothesis :

Prolotherapy provides improvement of cartilage based on COMP and UCTX-II levels and functional outcome among KOA patients

Detailed Description

Design :

Double-blind randomized trial

Randomization :

Simple Randomization generated by an online randomizer

Sample Size :

Difference between two means of primary outcome where

1. mean difference (μ 1 - μ 2 ) = 0.05

2. pool variance = 0.09

3. Z 1-α/2 = 1.95 with type 1 error 5%

4. 1-β = 1.282 with power 90%. Yielding 16 patients for each arm

Time Period of Recruitment September 2019- August 2020

Detailed Intervention

1. Intervention group : Prolotherapy given three times (Day-1, Day-29, and Day-57 )

2. Comparison group : Hyaluronate given five times (Day-1, Day-8, Day-15, Day-22, and Day-29.)

Outcome Measurement :

1. Cartilage Oligomeric Matrix Protein (COMP) Source of Sample : Median Cubital Vein Whole Blood Measurement : Enzyme-linked Immunoassay

2. Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II) Source of Sample : 50 cc of random urine sample Measurement : Enzyme-linked Immunoassay

3. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for functional Outcome (self-reported assessment)

Domains :

1. five elements of pain (score range 0-20),

2. two for stiffness (score range 0-8),

3. 17 for functional limitation (score range 0-68)

Classification :

0 - 24 : Mild 25 - 48 : Moderate 49 - 72 : Severe 73 - 96 : Extremely Severe

Statistical analysis :

1. Descriptive statistic to elaborate baseline characteristic

2. Assuming the baseline characteristic between groups are similar, the independent t-test will be conducted to see the differences between group, whereas Mann Whitney will be performed for non parametric data

3. Difference within group (baseline and last day) will be measured by paired-t test or wilcoxon for non parametric scenario

Study Timeline

• Study Start: 2019-09-01
• Primary Completion: 2020-04-30
• Study Completion: 2020-08-01
• Study First Submitted: 2020-09-07
• Study First Submitted QC: 2020-09-18
• Study First Posted: 2020-09-22
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-17
• Last Update Posted: 2020-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. The patient provides consent to be part of the research.
2. The diagnosis of Knee Osteoarthritis was made based on clinical criteria/radiology American College of Rheumatology (ACR) 2012 with radiology grading according to Kellgren-Lawrence 2-3

Exclusion Criteria

1. The Patient has received other forms of intraarticular injection therapy.
2. The patient has received Non Steroid Anti inflammation drug (NSAID) therapy for one week before the start of the intervention.
3. The patient has one or more contraindications for prolotherapy (e.g., Abscess, cellulitis, or septic arthritis).

Drop Out Criteria :

1. The patient has undergone a strenuous physical activity that precipitates a degree of complication (i.e., joint effusion).
2. The use of NSAID within one week after the intervention.
3. The patient does not adhere to the intervention.
4. The patient developed or being diagnosed with osteoarthritis or other forms of inflammatory disease in other joints.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prolotherapy	Prolotherapy	Prolotherapy injection is performed intra-articularly and extra-articularly by a physician. Intra-articular injection with 25% dextrose will be carried out with the following details: 5 mL of 40% dextrose, 2 mL of lidocaine, and 1 mL of aqua dest are inserted into the 10-mL syringe, then 5 mL are injected with the superolateral approach. An extra-articular injection with 15% dextrose will be carried out with the following details: in the 10-mL syringe 4 mL of 40% dextrose, 2 mL lidocaine, and 4 mL of distilled water are injected, to make a total of 30-40 mL injections. Treatment will be carried out on day 1st, 29th, and 57th.
Sodium Hyaluronate	Sodium Hyaluronate	Hyaluronate sodium injection is performed intra-articularly using 2 mL of Adant® Disposable. The treatment will be given five times, on day 1st, 8th, 15th, 22nd, and 29th

Primary Outcome Measures

Name	Time	Method
Cartilage Oligomeric Matrix Protein (COMP)	Measured on the first day before intervention and day 78 after the first dose of treatment in all groups	cartilage oligomeric matrix protein from whole blood measured using Enzyme-linked Immunoassay (ELISA). Mean difference between group will be assessed

Secondary Outcome Measures

Name	Time	Method
Functional Outcome	Measured on the first day before intervention and day 78 after the first injection on the prolotherapy group and Day 50 after the first injection for the hyaluronate group	the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index ) measuring three domains (pain, function limitation and stiffness) ranging from 0-96 of total score.
Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II)	Measured on the first day before intervention and day 78 after the first injection on the prolotherapy group and Day 50 after the first injection for the hyaluronate group	Urinary C-Terminal Telopeptides of Type II Collagen from urine sample measured using Enzyme-linked Immunoassay (ELISA)

Trial Locations

Locations (1)

Hasanuddin University, Faculty of Medicine; 🇮🇩 Makassar, South Sulawesi, Indonesia