Dataset Information

Efficacy and cost-effectiveness of Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis: protocol for a randomised placebo-controlled trial (the SCUlpTOR trial).

ABSTRACT:

Introduction

Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease. Intra-articular stem cell therapy is increasingly being used for treating KOA with little high-quality evidence to support its use. The aim of this study is to investigate the efficacy, safety and cost-effectiveness of allogeneic mesenchymal stem cells (Cymerus MSCs) for treating symptomatic tibiofemoral KOA and improving knee structure over 24 months.

Methods and analysis

The Stem Cell injections for symptomatic relief and strUctural improvement in people with Tibiofemoral knee OsteoaRthritis study is a phase III, multi-centre, parallel, superiority, randomised, double-blind, placebo-controlled trial, which will be conducted in Sydney and Hobart, Australia. 440 participants (220 per arm) aged over 40 years with painful KOA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) with medial minimum joint space width between 1 and 4 mm in the study knee will be recruited from the community and randomly allocated to receive either intra-articular MSCs or saline at baseline, week 3 and week 52. The coprimary outcomes will be the proportion of participants achieving patient-acceptable symptom state for knee pain at 24 months and quantitative central medial femorotibial compartment cartilage thickness change from baseline to 24 months. Main secondary outcomes include change in knee pain, Patient Global Assessment, physical function, quality of life and other structural changes. Additional data for cost-effectiveness analysis will also be recorded. Adverse events will be monitored throughout the study. The primary analysis will be conducted using modified intention-to-treat.

Ethics and dissemination

This protocol has been approved by The University of Sydney (USYD) Human Research Ethics Committee (HREC) #: 2020/119 and The University of Tasmania (UTAS) HREC #: H0021868. All participants will be required to provide informed consent. Dissemination will occur through conferences, social media, and scientific publications.

Trial registration numbers

Australian New Zealand Clinical Trials Registry (ACTRN12620000870954); U1111-1234-4897.

SUBMITTER: Liu X

PROVIDER: S-EPMC8633994 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOsteoarthritis (OA) is the most common joint disease, and is most frequently seen in the knees. However, there is no effective therapy to relieve the progression of knee OA. Metformin is a safe, well-tolerated oral medication that is extensively used as first-line therapy for type 2 diabetes. Previous observational studies and basic researches suggested that metformin may have protective effects on knee OA, which needs to be verified by clinical trials. This study, therefore, aims to examine the effects of metformin versus placebo on knee cartilage volume loss and knee symptoms in overweight knee OA patients by a randomized controlled trial over 24 months.MethodsThis protocol describes a multicenter, randomized, double-blind, and placebo-controlled clinical trial aiming to recruit 262 overweight knee OA patients. Participants will be randomly allocated to the two arms of the study, receiving metformin hydrochloride sustained-release tablets or identical inert placebo for 24 months (start from 0.5 g/day for the first 2 weeks, and increase to 1 g/day for the second 2 weeks, and further increase to 2 g/day for the remaining period if tolerated). Primary outcomes will be changes in tibiofemoral cartilage volume and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score over 24 months. Secondary outcomes will be changes in visual analogue scale (VAS) knee pain, tibiofemoral cartilage defects, effusion-synovitis volume, and tibiofemoral bone marrow lesions maximum size over 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per-protocol analyses will be performed as the secondary analyses.DiscussionIf metformin is proved to slow knee cartilage volume loss and to relieve knee symptoms among overweight knee OA patients, it will have the potential to become a disease modifying drug for knee OA. Metformin is a convenient intervention with low cost, and its potential effects on slowing down the structural progression and relieving the symptoms of knee OA would effectively reduce the disease burden worldwide.Trial registrationClinicalTrials. gov NCT05034029 . Registered on 30 Sept 2021.

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