Perineural Prolotherapy in Chronic Knee Osteoarthritis Pain.

NCT07245121 | Recruiting

• 1 other identifier: 610/05-09-2025
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to test whether the addition of dextrose to perineural injections is superior to local anesthetic alone, as some initial data have indicated. To enhance the potential therapeutic effect, we will proceed to a 4-point injection technique, targeting 4 genicular nerves (superomedial, superolateral, inferomedial, recurrent peroneal genicular nerve) in a randomized controlled trial with two arms.

Conditions

Chronic Pain; Perineural Analgesia; Prolotherapy; Knee Osteoarthritis

Keywords

Perineural prolotherapy; Knee osteoarthritis; Chronic pain

Outcome Measures

Primary Outcomes (1)

• Pain Severity Score (PSS) at 15 days after the 3rd (last) infiltration

  The primary outcome will be estimated by the Brief Pain Inventory (BPI) score, a numerical scale used to assess pain. This score is the arithmetic average of four items related to pain intensity: worst pain, least pain, average pain, and current pain (SCORE RANGE: 0= No pain, 1-3= Mild pain, 4-6= Moderate pain, 7-10= Severe pain).

  15 days after the 3rd infiltration of the first participant up to 15 days after the 3rd infiltration of the last participant

Secondary Outcomes (6)

• Pain Severity Score (PSS) at baseline, 30 and 90 days after the 3rd infiltration

  A measurement before the first infiltration of the first participant up to 90 days after the 3rd infiltration of the last participant.

• Pain Interference Score (PIS)

  From before the first infiltration of the first participant up to 3 months after the last infiltration of the last participant.

• Short-term changes 24h after the first infiltration

  24 hours after the first infiltration of the first participant up to 24 hours after the first infiltration of the last participant.

• WOMAC Questionnaire

  Baseline, 15, 30 and 90 days after completion of the therapy of the first participant until 90 days after completion of therapy of the last participant.

• 30 seconds chair stand test (30CST)

  Baseline, 15, 30 and 90 days after completion of the therapy of the first participant until 90 days after completion of therapy of the last participant.

Other Outcomes (1)

• Subanalyses of the scales used

  Baseline, 15, 30 and 90 days after completion of the therapy of the first participant until 90 days after completion of therapy of the last participant

Study Arms (2)

Dextrose + Lidocaine group (group D+L)

ACTIVE COMPARATOR

In the Dextrose + Lidocaine group (group D+L) an ultrasound guided perineural injection of DW 5% and lidocaine 1% will be performed at the 4 genicular nerves (superomedial, superolateral, inferomedial, recurrent peroneal genicular nerve).

Drug: Dextrose 5% and Lidocaine

Lidocaine group (group L)

ACTIVE COMPARATOR

In the lidocaine group (group L) an ultrasound guided perineural injection of a solution of lidocaine 1% will be performed at the 4 genicular nerves (superomedial, superolateral, inferomedial, recurrent peroneal genicular nerve).

Drug: Lidocaine

Interventions

Dextrose 5% and Lidocaine DRUG

In the Dextrose + Lidocaine group (group D+L) a perineural infusion of a total volume of 8 ml of DW 5% and lidocaine 1% will be performed at the 4 genicular nerves (2ml per nerve), which will be prepared as follows: 4 ml of lidocaine 2%, with 1.2 ml of DW 35% and 2.8 ml of NaCl 0.9%. All perineural injections will be executed under ultrasound guidance 3 times (in 3 consecutive sessions): at their first assessment, 2 and 4 weeks later.

Dextrose + Lidocaine group (group D+L)

Lidocaine DRUG

In the Lidocaine group (group L) the respective infusion of a solution of 8 ml of lidocaine 1% at the 4 genicular nerves (2ml per nerve) will be prepared as follows: 4 ml of lidocaine 2% with 4 ml of NaCl 0.9%. The perineural injections in each group will be executed 3 times (in 3 consecutive sessions): at their first assessment, 2 and 4 weeks later.

Lidocaine group (group L)

Eligibility Criteria

• Age: 38 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients of both sexes
• Age \>38 years
• Body Mass Index (BMI) up to 42 kg/m2
• Diagnosis of knee osteoarthritis, according to the clinical criteria of the American College of Rheumatology. Osteoarthritis if the following combinations are present:
• A, B, C, D or A, B, E or A, D, E:
• A) Knee pain most days of the previous month B) Cracking during active joint movement C) Morning stiffness lasting at least 30 minutes D) Age at least 38 years E) Bone swelling of the affected knee on physical examination
• Chronic knee pain on the Numerical Rating Scale (NRS) \> 5 for at least 3 months prior to the study
• Grade 2 or 3 osteoarthritis, according to the Kellgern-Lawrence classification
• Pain, creaking, and stiffness in the knee joint that persists for at least three months prior to the study.

You may not qualify if:

• Any infection of the skin of the knee joint, such as cellulitis, or periarticular or intraarticular infection during the last 3 months
• Poorly controlled diabetes mellitus or connective tissue disease affecting the knee joint
• History of previous total knee arthroplasty or other knee surgery.
• History of periarticular or intraarticular injection of corticosteroids, local anesthetic, hyaluronic acid, platelet-rich plasma, radiofrequency, prolotherapy within the last trimester
• History of knee injury or fracture within the last 3 months
• History of acute lumbosacral radiculopathy or peripheral neuropathy, neurological, psychiatric disease
• Pain limited in the posterior aspect of the knee
• History of limb malignancy
• History of bleeding disorder
• Pregnancy
• Allergy to local anesthetics, needle phobia
• Difficulty communicating (severe hearing loss, dementia, language problems)
• Non-guaranteed transportation to hospital for treatments and re-evaluations

Sponsors & Collaborators

• National and Kapodistrian University of Athens: lead

Study Sites (1)

University General Hospital of Athens "Attikon" - National and Kapodistrian University of Athens Medical School

Athens, Attica, 124 62, Greece

RECRUITING

Related Publications (16)

• Kim DH, Choi SS, Yoon SH, Lee SH, Seo DK, Lee IG, Choi WJ, Shin JW. Ultrasound-Guided Genicular Nerve Block for Knee Osteoarthritis: A Double-Blind, Randomized Controlled Trial of Local Anesthetic Alone or in Combination with Corticosteroid. Pain Physician. 2018 Jan;21(1):41-52.

  PMID: 29357330 BACKGROUND

• Ahmed A, Arora D. Ultrasound-guided radiofrequency ablation of genicular nerves of knee for relief of intractable pain from knee osteoarthritis: a case series. Br J Pain. 2018 Aug;12(3):145-154. doi: 10.1177/2049463717730433. Epub 2017 Sep 19.

  PMID: 30057759 BACKGROUND

• Waluyo Y, Artika SR, Insani Nanda Wahyuni, Gunawan AMAK, Zainal ATF. Efficacy of Prolotherapy for Osteoarthritis: A Systematic Review. J Rehabil Med. 2023 Feb 27;55:jrm00372. doi: 10.2340/jrm.v55.2572.

  PMID: 36847731 BACKGROUND

• Farpour HR, Fereydooni F. Comparative effectiveness of intra-articular prolotherapy versus peri-articular prolotherapy on pain reduction and improving function in patients with knee osteoarthritis: A randomized clinical trial. Electron Physician. 2017 Nov 25;9(11):5663-5669. doi: 10.19082/5663. eCollection 2017 Nov.

  PMID: 29403602 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

• Rezasoltani Z, Taheri M, Mofrad MK, Mohajerani SA. Periarticular dextrose prolotherapy instead of intra-articular injection for pain and functional improvement in knee osteoarthritis. J Pain Res. 2017 May 17;10:1179-1187. doi: 10.2147/JPR.S127633. eCollection 2017.

  PMID: 28553139 BACKGROUND

• Ebnerasooli S, Barghi A, Nasseri K, Moghimi N. Peri-articular Dextrose Prolotherapy: Investigating the Effect of Injection Site on Knee Osteoarthritis Pain: A Double-Blind, Randomized, Clinical Trial. Anesth Pain Med. 2024 Mar 27;14(2):e140966. doi: 10.5812/aapm-140966. eCollection 2024 Apr.

  PMID: 39411379 BACKGROUND

• Ghai B, Kumar M, Makkar JK, Goni V. Comparison of ultrasound guided pulsed radiofrequency of genicular nerve with local anesthetic and steroid block for management of osteoarthritis knee pain. Korean J Pain. 2022 Apr 1;35(2):183-190. doi: 10.3344/kjp.2022.35.2.183.

  PMID: 35354681 BACKGROUND

• Chen JL, Chen CH, Cheng CH, Chen CC, Lin KY, Chen CPC. Can the addition of ultrasound-guided genicular nerve block using 5% dextrose water augment the effect of autologous platelet rich plasma in treating elderly patients with knee osteoarthritis? Biomed J. 2021 Dec;44(6 Suppl 1):S144-S153. doi: 10.1016/j.bj.2020.08.011. Epub 2020 Sep 1.

  PMID: 35289285 BACKGROUND

• Fu Y, Du Y, Li J, Xi Y, Ji W, Li T. Demonstrating the effectiveness of intra-articular prolotherapy combined with peri-articular perineural injection in knee osteoarthritis: a randomized controlled trial. J Orthop Surg Res. 2024 May 5;19(1):279. doi: 10.1186/s13018-024-04762-4.

  PMID: 38705988 BACKGROUND

• Bhargava M, Gaur R, Gonnade NM, Sarankumar G, Elhence A, Gahlot N. Comparing effectiveness of 3-needle approach versus 5-needle approach of genicular nerve block on pain and quality of life in chronic osteoarthritis of knee: a double blinded randomised controlled trial. BMC Musculoskelet Disord. 2024 Nov 29;25(1):978. doi: 10.1186/s12891-024-07938-5.

  PMID: 39614201 BACKGROUND

• Govender-Davies S, Davies L, Pillay-Addinall S. A cadaveric study investigating the spread of injectate following an interspace between the popliteal artery and the capsule of the posterior knee block in a neonatal sample: a pilot study. Anat Cell Biol. 2024 Jun 30;57(2):229-237. doi: 10.5115/acb.23.274. Epub 2024 Mar 29.

  PMID: 38551026 BACKGROUND

• Yin W, Luo D, Xu W, Yang W, Jia S, Lin J. Effect of adductor canal block combined with infiltration between the popliteal artery and posterior capsular of the knee on chronic pain after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial. BMC Anesthesiol. 2024 Sep 10;24(1):320. doi: 10.1186/s12871-024-02707-2.

  PMID: 39256652 BACKGROUND

• Wu YT, Chen YP, Lam KHS, Reeves KD, Lin JA, Kuo CY. Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation. Life (Basel). 2022 Jun 2;12(6):832. doi: 10.3390/life12060832.

  PMID: 35743863 BACKGROUND

• Kim H, Kim HJ, Jung YH, Do W, Kim EJ. The effect of perineural injection therapy on neuropathic pain: a retrospective study. J Dent Anesth Pain Med. 2024 Feb;24(1):47-56. doi: 10.17245/jdapm.2024.24.1.47. Epub 2024 Feb 1.

  PMID: 38362256 BACKGROUND

• Yildirim Uslu E. Ultrasound-Guided Perineural Dextrose Injection for Superior Cluneal Nerve Neuropathy Treatment. Cureus. 2024 Sep 26;16(9):e70229. doi: 10.7759/cureus.70229. eCollection 2024 Sep.

  PMID: 39463523 BACKGROUND

MeSH Terms

Conditions

Chronic Pain; Osteoarthritis, Knee

Interventions

Glucose; Lidocaine

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Hexoses; Monosaccharides; Sugars; Carbohydrates; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Study Officials

• Konstantinos Kalimeris, Assoc Prof of Anesthesiology

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Theodosios Saranteas, Professor of Anesthesiology

  National and Kapodistrian University of Athens

  STUDY CHAIR

• Andreas Maurogenis, Assoc Prof of Anesthesiology

  National and Kapodistrian University of Athens

  STUDY CHAIR

Central Study Contacts

Konstantinos Kalimeris MD, PhD, Associate Professor of Anesthesiology, Associate Professor

CONTACT

+302105831997; kkalimeris@med.uoa.gr

Vasileios Boviatsis MD, Msc, PhD candidate

CONTACT

+306982925945; billboviatsis@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: November 24, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

GR (1)