. 2021 Nov 29;11(11):e056382.

doi: 10.1136/bmjopen-2021-056382.

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)

Xiaoqian Liu^{1

2}, Sarah Robbins^{1

2}, Xia Wang^{1

2}, Sonika Virk^{1

2}, Karen Schuck^{1

2}, Leticia A Deveza^{1

2}, Win Min Oo^{1

2}, Kirsty Carmichael³, Benny Antony³, Felix Eckstein^{4

5}, Wolfgang Wirth^{4

5}, Christopher Little⁶, James Linklater⁷, Anthony Harris⁸, David Humphries⁹, R O'Connell¹⁰, Gillian Heller¹⁰, Thomas Buttel¹¹, Stefan Lohmander¹², Changhai Ding^{3

13}, David J Hunter^{14

2

13}

Affiliations

¹ Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
² Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
⁴ Institute of Anatomy and Cell Biology and Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria.
⁵ Chondrometrics GmbH, Freilassing, Germany.
⁶ Raymond Purves Bone and Joint Research Labs, Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
⁷ Castlereagh Imaging, St Leonards, Sydney, New South Wales, Australia.
⁸ Centre for Health Economics, Monash University, Clayton, Victoria, Australia.
⁹ School of Medicine, College of Health and Medicine, University of Tasmania Faculty of Health, Hobart, Tasmania, Australia.
¹⁰ NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
¹¹ Representative of People with Knee Osteoarthritis, Sydney, New South Wales, Australia.
¹² Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.
¹³ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
¹⁴ Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia david.hunter@sydney.edu.au.

PMID: 34845081
PMCID: PMC8633994
DOI: 10.1136/bmjopen-2021-056382

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)

Xiaoqian Liu et al. BMJ Open. 2021.

. 2021 Nov 29;11(11):e056382.

doi: 10.1136/bmjopen-2021-056382.

Authors

Affiliations

¹ Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
² Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.
³ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
⁴ Institute of Anatomy and Cell Biology and Ludwig Boltzmann Institute for Arthritis and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria.
⁵ Chondrometrics GmbH, Freilassing, Germany.
⁶ Raymond Purves Bone and Joint Research Labs, Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
⁷ Castlereagh Imaging, St Leonards, Sydney, New South Wales, Australia.
⁸ Centre for Health Economics, Monash University, Clayton, Victoria, Australia.
⁹ School of Medicine, College of Health and Medicine, University of Tasmania Faculty of Health, Hobart, Tasmania, Australia.
¹⁰ NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales, Australia.
¹¹ Representative of People with Knee Osteoarthritis, Sydney, New South Wales, Australia.
¹² Department of Clinical Sciences Lund, Orthopaedics, Lund University, Lund, Sweden.
¹³ Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
¹⁴ Department of Rheumatology, Royal North Shore Hospital, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia david.hunter@sydney.edu.au.

PMID: 34845081
PMCID: PMC8633994
DOI: 10.1136/bmjopen-2021-056382

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.

Keywords: clinical trials; knee; rheumatology.

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Conflict of interest statement

Competing interests: DJH is supported by an NHMRC Investigator Grant and provides consulting advice for Merck Serono, TLC Bio, Tissuegene and Pfizer. CL has provided consulting advice for Merck Serono and Galapagos Pharmaceuticals, and receives research funding from numerous pharmaceutical companies through specific services/testing contract research agreements between and managed by The University of Sydney or the NSLHD. SL provides consulting advice for Arthro Therapeutics, Pfizer and Synartro. LAD has received partial reimbursement of a conference registration by Pfizer. FE is CEO/CMO and co-owner of Chondrometrics GmbH, and he has provided consulting services to Merck KGaA, Abbvie, Samumed, Kolon-Tissuegene, Servier, Galapagos, Roche, Novartis, ICM and HealthLink. WW is co-owner of Chondrometrics GmbH, and has provided consulting services to Galapagos.

Figures

**Figure 1**
Flow diagram of the study protocol.

See this image and copyright information in PMC

References

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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)

Affiliations

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)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources