Prolotherapy Intervention Effect in Patient With Knee Osteoarthritis

NCT04557943 | Completed Phase 4

• 1 other identifier: 2708201904
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Conditions

Knee Osteoarthritis

Keywords

Knee Osteoarthritis; COMP; uCTX-II; Prolotherapy; Functional Outcome

Outcome Measures

Primary Outcomes (1)

• Cartilage Oligomeric Matrix Protein (COMP)

  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 Outcomes (2)

• 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

• 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

Study Arms (2)

Sodium Hyaluronate

ACTIVE COMPARATOR

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

Prolotherapy

EXPERIMENTAL

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

Interventions

Prolotherapy 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.

Also known as: Prolotherapy Dextrose

Prolotherapy

Sodium Hyaluronate 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

Also known as: 2 mL Sodium Hyaluronate

Sodium Hyaluronate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient provides consent to be part of the research.
• 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

You may not qualify if:

• The Patient has received other forms of intraarticular injection therapy.
• The patient has received Non Steroid Anti inflammation drug (NSAID) therapy for one week before the start of the intervention.
• The patient has one or more contraindications for prolotherapy (e.g., Abscess, cellulitis, or septic arthritis).
• Drop Out Criteria :
• The patient has undergone a strenuous physical activity that precipitates a degree of complication (i.e., joint effusion).
• The use of NSAID within one week after the intervention.
• The patient does not adhere to the intervention.
• The patient developed or being diagnosed with osteoarthritis or other forms of inflammatory disease in other joints.

Sponsors & Collaborators

• Hasanuddin University: lead

Study Sites (1)

Hasanuddin University, Faculty of Medicine

Makassar, South Sulawesi, 90245, Indonesia

Location

Related Publications (12)

• 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.

  PMID: 22515800 BACKGROUND

• 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.

  PMID: 25829954 BACKGROUND

• 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.

  PMID: 23690322 BACKGROUND

• 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.

  PMID: 31426856 BACKGROUND

• 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.

  PMID: 19384621 BACKGROUND

• 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.

  PMID: 12972471 BACKGROUND

• 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.

  PMID: 29662791 BACKGROUND

• 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.

  PMID: 22001901 BACKGROUND

• 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.

  PMID: 23423905 BACKGROUND

• 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.

  PMID: 28606459 BACKGROUND

• 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.

  PMID: 27058744 BACKGROUND

• 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.

  PMID: 27799816 BACKGROUND

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Prolotherapy; Hyaluronic Acid

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Complementary Therapies; Therapeutics; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Yose Waluyo, MD

  Hasanuddin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher

Model Details: This study involves two arms assigned randomly for receiving different treatment. One arm for Prolotherapy and Sodium Hyaluronate in the comparison group.

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 22, 2020
• Study Start: September 1, 2019
• Primary Completion: April 30, 2020
• Study Completion: August 1, 2020
• Last Updated: November 19, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)