Prolotherapy Intervention Effect in Patient With Knee Osteoarthritis

November 17, 2020 updated by: Bumi Herman, Hasanuddin University

The Level of Cartilage Oligomeric Matrix Protein (COMP) and Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II) After Prolotherapy Intervention and The Functional Outcome in Patient With Knee Osteoarthritis

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Indonesia
    • South Sulawesi
      • Makassar, South Sulawesi, Indonesia, 90245
        • Hasanuddin University, Faculty of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Drug: Sodium Hyaluronate
Hyaluronan 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
Other Names:
  • 2 mL Sodium Hyaluronate
Experimental: 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.
Drug: 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.

Other Names:
  • Prolotherapy Dextrose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cartilage Oligomeric Matrix Protein (COMP)
Time Frame: 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
Measured on the first day before intervention and day 78 after the first dose of treatment in all groups

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Urinary C-Terminal Telopeptides of Type II Collagen (uCTX-II)
Time Frame: 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)
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
Functional Outcome
Time Frame: 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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hasanuddin University

Investigators

  • Principal Investigator: Yose Waluyo, MD, Hasanuddin University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2019

Primary Completion (Actual)

April 30, 2020

Study Completion (Actual)

August 1, 2020

Study Registration Dates

First Submitted

September 7, 2020

First Submitted That Met QC Criteria

September 18, 2020

First Posted (Actual)

September 22, 2020

Study Record Updates

Last Update Posted (Actual)

November 19, 2020

Last Update Submitted That Met QC Criteria

November 17, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2708201904

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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