Genetic studies of osteoarthritis
Gout Treatment Trial Phase 2 (funded by Arthritis Research UK) - Two Year Randomised Controlled Trial of a Nurse Led Package of Care
Objectives: To determine in community-based patients with untreated or under treated gout the effectiveness and cost effectiveness of a nurse-led complex intervention that reflects recommended best practice (including urate lowering therapy (ULT) to reduce serum uric acid (SUA) levels to <360 μmol/l).
Nottingham Gout Treatment Trial Phase 1 (funded by Arthritis Research UK)
During phase 1 of the trial we: (1) explored illness perceptions and possible barriers to care in patients with gout, nurses and doctors; and (2) undertook a proof-of-concept research clinic to demonstrate that the majority of people with gout can have their disease effectively treated and "cured" by a nurse led intervention that applies currently available treatments and lifestyle advice. The success of this feasibility study resulted in the funding of a further 2 year randomised controlled trial (Phase 2) to examine the efficacy of the nurse led intervention in the Nottinghamshire community.
Between 2002 and 2006 we characterised a large group of participants for genetic association and gene-environmental interaction studies of knee and hip OA - the Nottingham Genetics of Osteoarthritis and Lifestyle ("GOAL" study). The GOAL database was established in collaboration with AstraZeneca UK and comprises detailed information (including lifestyle factors from age 20 onwards; x-rays of knees, hips, hands; DNA) on 1100 patients with clinically severe knee OA, 1000 patients with clinically severe hip OA, and 1200 matched controls with no hip or knee OA (age range 45-80 years).
The GOAL database continues to be utilised to: 1] investigate gene-environmental interactions using established candidate genes 2] undertake association studies to retest published genetic associations for knee or hip OA; 3] undertake non-genetic substudies to examine specific hypotheses related to OA and chondrocalcinosis.
GOGO / arcOGEN
In addition to GOAL, we are one of 6 centres (4 US, 2 UK) involved in the Genetics of Generalised Osteoarthritis (GOGO) study to determine genetic associations with generalised OA, hip, knee and spinal (intervertebral and apophyseal) OA.
We were also one of several centres in the UK which recruited participants to take part in the arcOGEN study, funded by Arthritis Research UK to identify genes responsible for increasing the risk of people developing knee and hip OA.
We are continuing to recruit participants with clinically severe knee and hip OA to expand the Nottingham collection of OA participants, and undertake studies to investigate candidate genes/associations for OA in collaboration particularly with Units in London (Ana Valdes, Tim Spector) and Oxford (Nigel Arden).
Nottingham Osteoarthritis Biomarker Study
We are also currently collecting synovial fluid, blood and urine samples from people with knee OA and also from control participants with normal knees to measure the differences in the composition of the samples between the two groups. It is hoped that the identification of these changes will allow us to better understand the metabolic changes that occur in OA.
Evidence based medicine
The group has an established record in evidence based medicine research. This ranges from meta-analyses of randomised controlled trials (RCTs) to systematic reviews of observational studies.
Identifying treatment responders to a topical non-steroidal anti-inflammatory drug (NSAID) or topical capsaicin in painful knee osteoarthritis: a pilot series of n-of-1 trials
Men and women with painful knee osteoarthritis were recruited to this pilot n-of-1 trial series. Participants underwent up to three treatment cycles, each consisting of four weeks each of 5% ibuprofen gel and 0.025% capsaicin cream in a randomly determined order. Change from baseline pain scores per treatment period were analysed for each participant to identify individuals with a treatment response to ibuprofen gel or capsaicin cream (primary). Secondary objectives were (1) to examine pre-treatment differences between responders and non-responders, specifically focusing on synovial changes by ultrasonography and neuropathic-like characteristics of pain in osteoarthritis; (2) to gather sufficient information to guide a definitive trial of predictors of response; and (3) to offer recommendations on the use of n-of-1 trials for individualised (precision) medicine in osteoarthritis.
- The placebo effect and its determinants in fibromyalgia RCts
- Complementary medicine and its contextual effect in OA RCTs
- Quantitative sensory testing in human OA
- Risk synthesis and prediction in knee OA
- Smoking and progression of OA
- Safety of topical non-steroidal anti-inflammatory drugs (NSAIDs)