Intraarticular Gold Microparticles for Knee Osteoarthritis

Official title

Intraarticular Gold Microparticles for Knee Osteoarthritis. A Randomized Trial

Overview

The investigators have shown in three pilot studies that intra-articular metallic gold microparticles can reduce knee osteoarthritis pain for up to two years. These results are noteworthy considering the growing number of older adults who suffer from osteoarthritis pain, which contributes to increased demand on healthcare resources. Demonstrating effective treatment could alleviate this burden for a significant portion of the aging population. The specific aim is to evaluate whether intra-articular metallic gold microparticles are superior to placebo in reducing the need for additional treatment in patients with knee osteoarthritis within one year. The investigators will test the hypothesis that intra-articular metallic gold microparticles reduce subsequent treatment events by more than 50% compared to placebo during this period.

Detailed description

To test the superiority of metallic gold microparticles over a placebo, 240 patients will be included in a randomized, double-blind, controlled trial. This process will take place over a period of 1-2 years. The study will follow the CONSORT Guidelines and comply with the Danish Data Protection Agency. The investigators will handle all data in an electronic form, including demographics and all outcome measures. The investigators will use an electronic Case Report Form (CRF). The management of data will be handled according to the Danish Data Protection Agency's guidelines. The host for data will be physically located at Aalborg University Research Data host, and at North Denmark Region, q-drive host, and follow the Guidelines from The Danish Protection Agency. The schedule for randomization will be randomly generated using a computer before the initiation of the trial. The medical doctor will be blind to group allocation and will not be involved in providing the metallic gold microparticles or placebo. The participants and the medical doctor performing follow-up will be blind to group allocation.

All patients will receive either intra-articular metallic gold microparticles and HA or HA alone. With the use of 2 cc syringe, the investigators will perform intra-articular injection using the standard approach for knee puncture and injection. For intervention, 20 mg metallic gold microparticles (72.000 particles, 20-40 µm) will be injected into the joint using 2 mL hyaluronic acid. For control, 2 mL of hyaluronic acid will be injected into the joint. A centralized computer-generated randomization will allocate to either 2 cc of hyaluronic acid with or without 20 mg metallic gold microparticles.

At the end of the trial, the patients in the control group will receive the intervention treatment with metallic gold microparticles.

Interventions

• Other 20 mg metallic gold microparticles (72.000 particles, 20-40 µm) will be injected into the knee joint using 2 mL hyaluronic acid.
  20 mg metallic gold microparticles (72.000 particles, 20-40 µm) will be injected into the knee joint using 2 mL hyaluronic acid.
• Other Intervention
  20 mg metallic gold microparticles (72.000 particles, 20-40 µm) will be injected into the knee joint using 2 mL hyaluronic acid.

Primary outcome measures

• The primary outcome is any additional treatment event such as, re-referral, intra-articular injection, arthroscopy or any knee replacement surgery within 1 year. [Time frame: 1 year]

Secondary outcome measures (4)

• The PainDetect questionnaire [Time frame: 1 year]
• The Western Ontario and McMaster Universities Arthritis Index (WOMAC) [Time frame: 1 year]
• The quality of life score EQ-5D-5L [Time frame: 1 yar]
• Proteomic analysis of synovial fluid and serum [Time frame: 8 weeks]

Eligibility criteria

Inclusion criteria

• more than 6 months of knee pain without efficacy on pain of conservative treatment, radiographic knee osteoarthritis according to Kellgren-Lawrence grade 1-4, and age ≥18years

Exclusion criteria

• malalignment, indication for knee replacement surgery, malignancy, active infection and antibiotic treatment, active treatment with steroids, biological or other anti-Rheumatic medication, inability to comply with the protocol, inadequacy in the written and spoken national language

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Factorial

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Barfod KW, Blond L, Mikkelsen RK, Bagge J, Holmich LR, Kallemose T, Troelsen A, Holmich P. Treatment of knee osteoarthritis with a single injection of autologous micro-fragmented adipose tissue is not superior to a placebo saline injection: a blinded randomised controlled trial with 2-year follow-up. Br J Sports Med. 2025 Aug 26;59(17):1219-1227. doi: 10.1136/bjsports-2024-108732. PMID 40101939
• Kim KI, Kim MS, Kim JH. Intra-articular Injection of Autologous Adipose-Derived Stem Cells or Stromal Vascular Fractions: Are They Effective for Patients With Knee Osteoarthritis? A Systematic Review With Meta-analysis of Randomized Controlled Trials. Am J Sports Med. 2023 Mar;51(3):837-848. doi: 10.1177/03635465211053893. Epub 2022 Jan 12. PMID 35019764
• Peck J, Slovek A, Miro P, Vij N, Traube B, Lee C, Berger AA, Kassem H, Kaye AD, Sherman WF, Abd-Elsayed A. A Comprehensive Review of Viscosupplementation in Osteoarthritis of the Knee. Orthop Rev (Pavia). 2021 Jul 10;13(2):25549. doi: 10.52965/001c.25549. eCollection 2021. PMID 34745480
• Pereira TV, Juni P, Saadat P, Xing D, Yao L, Bobos P, Agarwal A, Hincapie CA, da Costa BR. Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis. BMJ. 2022 Jul 6;378:e069722. doi: 10.1136/bmj-2022-069722. PMID 36333100
• Richard MJ, Driban JB, McAlindon TE. Pharmaceutical treatment of osteoarthritis. Osteoarthritis Cartilage. 2023 Apr;31(4):458-466. doi: 10.1016/j.joca.2022.11.005. Epub 2022 Nov 19. PMID 36414224
• Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra SMA, Kraus VB, Lohmander LS, Abbott JH, Bhandari M, Blanco FJ, Espinosa R, Haugen IK, Lin J, Mandl LA, Moilanen E, Nakamura N, Snyder-Mackler L, Trojian T, Underwood M, McAlindon TE. OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1 PMID 31278997
• Altman RD, Devji T, Bhandari M, Fierlinger A, Niazi F, Christensen R. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum. 2016 Oct;46(2):151-159. doi: 10.1016/j.semarthrit.2016.04.003. Epub 2016 Apr 27. PMID 27238876
• Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013 Feb;41(2):356-64. doi: 10.1177/0363546512471299. Epub 2013 Jan 8. PMID 23299850

Identifiers

NCT: NCT07202390 · GAIN XVI Knee RCT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗