Knee Osteoarthritis
Conditions
Keywords
Intraarticular gold; knee osteoarthritis
Brief summary
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
OTHER20 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.
OTHERIntervention
20 mg metallic gold microparticles (72.000 particles, 20-40 µm) will be injected into the knee joint using 2 mL hyaluronic acid.
Sponsors
Aalborg University
Northern Orthopaedic Division, Denmark
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary outcome is any additional treatment event such as, re-referral, intra-articular injection, arthroscopy or any knee replacement surgery within 1 year. | 1 year | Time to event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The PainDetect questionnaire | 1 year | The PainDetect questionnaire (Freynhagen et al., 2006) includes three components: gradation of pain, pain course pattern, and radiating pain. Gradation is measured by seven patient-scored questions on a 0 to 5 scale (0 = never; 5 = very strongly). Pain course pattern is assessed with one question where patients select one of four images, each representing a specific score (0, -1, or +1; two images may score +1). Radiating pain is determined by a yes (score +2) or no (score 0) response. Total scores span from -1 (no pain symptoms) to 38 (severe pain symptoms). |
| The Western Ontario and McMaster Universities Arthritis Index (WOMAC) | 1 year | The WOMAC questionnaire includes 24 questions: 5 for pain, 2 for stiffness, and 17 for physical function, each scored on a 5-point scale from 0 (none) to 4 (extreme). The summarized score span from 0 (no symptoms) to 96 (severe symptoms). |
| The quality of life score EQ-5D-5L | 1 yar | The EQ-5D-5L (33) consists of two parts, a descriptive system and the EQ VAS. The descriptive system measures five dimensions of health: MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN / DISCOMFORT and ANXIETY / DEPRESSION. Each dimension has five response levels: no problems, slight problems, moderate problems, severe problems, unable to/extreme problems. Responses are coded as single-digit numbers expressing the severity level selected in each dimension. For instance, 'slight problems' (e.g. 'I have slight problems in walking about') is always coded as '2'. The digits for the five dimensions can be combined in a 5-digit code that describes the respondent's health state profile; for instance, 21111 means slight problems in the mobility dimension and no problems in any of the other dimensions. The EQ VAS records the respondent's overall current health on a vertical visual analogue scale from 0 to 100, where 0 is The best health you can imagine and 100 The worst health you can imagine |
| Proteomic analysis of synovial fluid and serum | 8 weeks | The analyses of the proteomic primary raw data output from synovial fluid and serum obtained before and 8 weeks after treatment in both arms will be searched against spectral databases generated by fractionated pooled samples using human reference proteome database in Biognosys Spectronaut (Schaab et al., 2012) and using statistical analysis (Koh et al., 2019). Quantitative proteome analysis of synovial and serum samples will be accomplished by discovery proteomics using DIA-PASEF (Meier et al., 2020). Functional association of significantly regulated proteins in synovial fluid and serum with gene ontology and function will be asessed by Metascape. |
Contacts
Primary ContactSten Rasmussen, M.D., M.B.A., Ph.D.
Backup ContactAllan Stensballe, cand.scient., Ph.D.
Outcome results
None listed