Improving Prevention and Treatment for Patients with Musculoskeletal Conditions.

Lead Research Organisation: University College London

Abstract

VIDEO and PACINO are two of our current clinical trials which aim to find better ways of treating patients with musculoskeletal conditions.||In the VIDEO trial patients with osteoarthritis of the knee are randomised to either daily Vitamin D or placebo capsules for three years. We want to find out whether Vitamin D will slow down the rate of narrowing of the joint space width in the knee. Patients have X-rays of their knee at the start of the trial and after three years of therapy and complete regular questionnaires describing their pain and disability. If Vitamin D is found to be effective we hope this will improve pain, function and the need for knee replacement surgery for these patients.||PACINO is a trial in patients who have a fracture of the lower leg (tibia) which is not healing. The usual surgical procedure after removing areas of damaged bone is to drill holes in the healthy bone where the two bones meet and fill these holes with the patients bone marrow to try to encourage the growth of new bone to fill the gap. We want to find out whether inserting stem cells grown from the patients bone marrow will make the new bone grow faster. Patients would welcome any decrease in the time they have to spend wearing a metal frame to support their unhealed fracture.

Technical Summary

The aim of the programme is to improve prevention and treatment for patients with musculoskeletal conditions. These are a major problem both nationally and internationally with a high burden of disability, and will become increasingly important as a consequence of the ageing population.||Arthritis Research UK is one of the largest medical research charities in the UK, funding research into the causes, consequences and treatment of musculoskeletal conditions. In 2008 Arthritis Research UK launched their clinical studies initiative to develop a comprehensive research programme in partnership with the UK Clinical Research Network (CRN), industry and other funders (such as NIHR) that would permit the testing of both new and existing interventions, based on a nationally agreed and scientifically robust research agenda, across the major disease areas of the charitys interests. In achieving this, there would be a transformation of clinical practice in areas of relevance which would drive both knowledge advance and quality of care. All their UK funded trials will be conducted by UKCRC registered trials units. The charity has funded a senior statistician post at the CTU since 2001 to advise researchers developing proposals for these clinical studies.||Osteoarthritis is a common disorder, and at present there are no effective treatments that alter disease pathology. Management of osteoarthritis is primarily aimed at symptom control with the aim to retain or improve joint function. Epidemiological data suggest that low dietary intake of vitamin D and low serum 25-hydroxyvitamin D3 levels are associated with radiological progression in knee osteoarthritis. VIDEO is a three year randomised, double-blind, placebo controlled trial funded by Arthritis Research UK to determine whether vitamin D supplementation of cholecalciferol 800 IU daily can reduce the rate of disease progression and improve symptoms in participants with knee osteoarthritis. The primary outcome measure is radiological progression with secondary endpoints being symptoms and quality of life assessments. As Vitamin D supplementation is safe and cheap, any proven benefit in the management of osteoarthritis will have important relevance to healthcare in the elderly.||Since 2007 the Royal National Orthopaedic Hospital have funded a statistician post to at the CTU to work on orthopaedic studies. A strong research theme of the Royal National Orthopaedic Hospital is a regenerative approach to lesions of cartilage, bone and tendon using cell-based therapies. If such an approach can be made to work this would reduce the need for reconstructive surgery and improve quality of life by reducing the amount of time the patient has to spend with their leg in a metal frame. RNOH have secured MRC funding to conduct a trial (PACINO) of autologous mesenchymal stem cells in fracture non-union. At the end of the trial we will use proteomics to correlate clinical response with cell phenotype. This should enable us to refine cell culture processes, and hence to develop more effective treatments for future trials.||A Phase II trial (SCARAB) of autologous bone marrow derived mesenchymal stem cells mixed with bone stock to improve the regeneration of bone adjacent to the implant in revision hip surgery is being planned. The failure rate of revision hip surgery is high, 25-50% of revision procedures fail, and increasing the regeneration of bone within the impacted graft is crucial for a successful outcome.

Publications

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Amiri AR (2013) Level of evidence of clinical spinal research and its correlation with journal impact factor. in The spine journal : official journal of the North American Spine Society

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Amiri AR (2013) Postoperative spinal epidural hematoma (SEH): incidence, risk factors, onset, and management. in The spine journal : official journal of the North American Spine Society

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Amiri AR (2014) Does source of funding and conflict of interest influence the outcome and quality of spinal research? in The spine journal : official journal of the North American Spine Society

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Arden N. K. (2014) EFFECT OF VITAMIN D SUPPLEMENTATION ON RADIOGRAPHIC KNEE OSTEOARTHRITIS in OSTEOARTHRITIS AND CARTILAGE

 
Description Citation in Cochrane review
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in systematic reviews
Impact Rehabilitation following lumbar disc surgery
URL http://www.ncbi.nlm.nih.gov/pubmed/24627325
 
Description Citation in review article
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in clinical reviews
Impact Pharmacological treatments for osteoarthritis of the hand
URL http://www.ncbi.nlm.nih.gov/pubmed/?term=24468932
 
Description MRC Hub Network Surgical Specialist Methodology workshop at the Royal College of Surgeons of England
Geographic Reach National 
Policy Influence Type Participation in a national consultation
Impact Improvements in the quality of surgical research
 
Description HTA , TARVA
Amount £1,297,038 (GBP)
Funding ID 12/35/27 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 11/2013 
End 05/2018
 
Description UCL Comprehensive Clinical Trials Unit 
Organisation University College London
Department Comprehensive Clinical Trials Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution I was seconded 0.8 FTE to the UCL Comprehensive Clinical Trials Unit as Head of Statistics until 2016. I stood down as Head of Statistics in 2016 and continued to work half time. I retired in December 2020.
Collaborator Contribution All new funding applications for musculoskeletal trials are collaborations with UCL CCTU
Impact A number of funding applications are in development.
Start Year 2011
 
Title TARVA 
Description TARVA is a randomised clinical trial comparing ankle replacement and ankle arthrodesis (fusion) in patients aged 50-85 with end-stage ankle arthritis 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Our main objectives are : 1.to determine which treatment offers better pain free function and quality of life, fewer complications and best value for money; 2.to disseminate the trial findings to the public through the patient group involved with our research as well as through peer reviewed journals, conferences, seminars and meetings. 
URL http://anklearthritis.co.uk
 
Title VIDEO 
Description Vitamin D supplementation may reduce the rate of disease progression and improve symptoms in participants with knee osteoarthritis. 
Type Preventative Intervention - Nutrition and Chemoprevention
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2013
Development Status Closed
Clinical Trial? Yes
Impact None yet 
URL http://www.isrctn.com/ISRCTN94818153
 
Description Workshop to develop guidance for internal pilot studies 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was a workshop to optimise the design and evaluation of internal pilot work to inform efficient randomised controlled trials. I presented a vignette describing the internal pilot phase and the progression criteria for the TARVA trial. The workshop was funded by the MRC Hubs for Trials Methodology research. A paper summarising the discussion is in preparation
Year(s) Of Engagement Activity 2014