Prolotherapy Intervention Effect in Patient With Knee Osteoarthritis

NCT ID: NCT04557943

Last Updated: 2020-11-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-01

Study Completion Date

2020-08-01

Brief Summary

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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

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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

Conditions

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Knee Osteoarthritis

Keywords

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Knee Osteoarthritis COMP uCTX-II Prolotherapy Functional Outcome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This study involves two arms assigned randomly for receiving different treatment. One arm for Prolotherapy and Sodium Hyaluronate in the comparison group.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors
A sealed envelope of the randomized sequence was given to the investigator and care provider, and participants were recruited consecutively according to the sequence. Participants were masked from the therapy by receiving treatment individually in different rooms and occasions. On the day of the assessment, the physician and laboratory technicians were blinded from group allocation

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Sodium Hyaluronate

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Prolotherapy

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type 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

Intervention Type DRUG

Other Intervention Names

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Prolotherapy Dextrose 2 mL Sodium Hyaluronate

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hasanuddin University

OTHER

Sponsor Role lead

Responsible Party

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Bumi Herman

Researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Yose Waluyo, MD

Role: PRINCIPAL_INVESTIGATOR

Hasanuddin University

Locations

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Hasanuddin University, Faculty of Medicine

Makassar, South Sulawesi, Indonesia

Site Status

Countries

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Indonesia

References

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Rabago D, Zgierska A, Fortney L, Kijowski R, Mundt M, Ryan M, Grettie J, Patterson JJ. Hypertonic dextrose injections (prolotherapy) for knee osteoarthritis: results of a single-arm uncontrolled study with 1-year follow-up. J Altern Complement Med. 2012 Apr;18(4):408-14. doi: 10.1089/acm.2011.0030.

Reference Type BACKGROUND
PMID: 22515800 (View on PubMed)

Eslamian F, Amouzandeh B. Therapeutic effects of prolotherapy with intra-articular dextrose injection in patients with moderate knee osteoarthritis: a single-arm study with 6 months follow up. Ther Adv Musculoskelet Dis. 2015 Apr;7(2):35-44. doi: 10.1177/1759720X14566618.

Reference Type BACKGROUND
PMID: 25829954 (View on PubMed)

Rabago D, Patterson JJ, Mundt M, Kijowski R, Grettie J, Segal NA, Zgierska A. Dextrose prolotherapy for knee osteoarthritis: a randomized controlled trial. Ann Fam Med. 2013 May-Jun;11(3):229-37. doi: 10.1370/afm.1504.

Reference Type BACKGROUND
PMID: 23690322 (View on PubMed)

Arias-Vazquez PI, Tovilla-Zarate CA, Legorreta-Ramirez BG, Burad Fonz W, Magana-Ricardez D, Gonzalez-Castro TB, Juarez-Rojop IE, Lopez-Narvaez ML. Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials. Adv Rheumatol. 2019 Aug 19;59(1):39. doi: 10.1186/s42358-019-0083-7.

Reference Type BACKGROUND
PMID: 31426856 (View on PubMed)

Scarpellini M, Lurati A, Vignati G, Marrazza MG, Telese F, Re K, Bellistri A. Biomarkers, type II collagen, glucosamine and chondroitin sulfate in osteoarthritis follow-up: the "Magenta osteoarthritis study". J Orthop Traumatol. 2008 Jun;9(2):81-7. doi: 10.1007/s10195-008-0007-5. Epub 2008 May 28.

Reference Type BACKGROUND
PMID: 19384621 (View on PubMed)

Garnero P, Conrozier T, Christgau S, Mathieu P, Delmas PD, Vignon E. Urinary type II collagen C-telopeptide levels are increased in patients with rapidly destructive hip osteoarthritis. Ann Rheum Dis. 2003 Oct;62(10):939-43. doi: 10.1136/ard.62.10.939.

Reference Type BACKGROUND
PMID: 12972471 (View on PubMed)

Huang M, Zhao J, Huang Y, Dai L, Zhang X. Meta-analysis of urinary C-terminal telopeptide of type II collagen as a biomarker in osteoarthritis diagnosis. J Orthop Translat. 2017 Aug 15;13:50-57. doi: 10.1016/j.jot.2017.06.005. eCollection 2018 Apr.

Reference Type BACKGROUND
PMID: 29662791 (View on PubMed)

Hoch JM, Mattacola CG, Medina McKeon JM, Howard JS, Lattermann C. Serum cartilage oligomeric matrix protein (sCOMP) is elevated in patients with knee osteoarthritis: a systematic review and meta-analysis. Osteoarthritis Cartilage. 2011 Dec;19(12):1396-404. doi: 10.1016/j.joca.2011.09.005. Epub 2011 Oct 5.

Reference Type BACKGROUND
PMID: 22001901 (View on PubMed)

Verma P, Dalal K. Serum cartilage oligomeric matrix protein (COMP) in knee osteoarthritis: a novel diagnostic and prognostic biomarker. J Orthop Res. 2013 Jul;31(7):999-1006. doi: 10.1002/jor.22324. Epub 2013 Feb 19.

Reference Type BACKGROUND
PMID: 23423905 (View on PubMed)

Shewale AR, Barnes CL, Fischbach LA, Ounpraseuth ST, Painter JT, Martin BC. Comparison of Low-, Moderate-, and High-Molecular-Weight Hyaluronic Acid Injections in Delaying Time to Knee Surgery. J Arthroplasty. 2017 Oct;32(10):2952-2957.e21. doi: 10.1016/j.arth.2017.04.041. Epub 2017 May 2.

Reference Type BACKGROUND
PMID: 28606459 (View on PubMed)

Topol GA, Podesta LA, Reeves KD, Giraldo MM, Johnson LL, Grasso R, Jamin A, Clark T, Rabago D. Chondrogenic Effect of Intra-articular Hypertonic-Dextrose (Prolotherapy) in Severe Knee Osteoarthritis. PM R. 2016 Nov;8(11):1072-1082. doi: 10.1016/j.pmrj.2016.03.008. Epub 2016 Apr 4.

Reference Type BACKGROUND
PMID: 27058744 (View on PubMed)

Hung CY, Hsiao MY, Chang KV, Han DS, Wang TG. Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. J Pain Res. 2016 Oct 18;9:847-857. doi: 10.2147/JPR.S118669. eCollection 2016.

Reference Type BACKGROUND
PMID: 27799816 (View on PubMed)

Other Identifiers

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2708201904

Identifier Type: -

Identifier Source: org_study_id