The Effect of Tart Cherry Juice on Risk of Gout Attacks

Study Overview
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Brief Summary
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The purpose of this study is to determine whether consuming tart cherry juice daily for 12 months reduces the risk of gout attacks during this period. Individuals with an existing gout diagnosis and who have experienced at least one gout flare in the past year will be recruited to participate in this study.

Detailed Description
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Gout is a painful and often debilitating condition affecting around 3% of adults in the UK. It is a type of inflammatory arthritis caused by high levels of uric acid which is deposited as crystals in joints, resulting in painful gout flares. Cherries and cherry products have received attention for their possible role in gout management owing to their anti-inflammatory and anti-oxidant properties. Their consumption has been associated with a lower risk of gout attacks in one observational study. The consumption of cherries is also endorsed by several gout information websites and in the British Society of Rheumatology's 2017 guidelines for the management of gout. However, there is limited evidence underpinning these claims and existing studies tend to be short in duration and have small participant numbers. Gout attacks are sporadic in nature and so a long-term trial is required to clarify the therapeutic effect of cherries on gout attack risk. The investigators are aiming to recruit 120 participants who have had at least one gout flare in the previous 12 months. Using the work of Rothenbacher et al., 2011, the chance of these individuals experiencing at least one attack in the next 12 months has been calculated at 11%. It is predicted that treatment with daily cherry juice consumption will reduce gout flare recurrence (primary outcome measure) to 1/4 of the rate of the actual recurrence i.e. to 2.7%. Using these figures, a sample size of 93 participants would provide power of 0.95 at a significance level of 0.05. A sample size of 120 participants allows for an approximate 20% attrition rate. Participants will consume either 30 mL tart cherry juice (CherryActive) diluted to 250 mL with water or a fruit-flavoured placebo drink daily with breakfast for 12 months. Participants will be followed up at 6 and 12 months at the investigators' laboratory to study changes in gout flare frequency and intensity, uric acid levels and levels of inflammation. This will help determine if tart cherry juice could help reduce or even prevent gout attacks. Additionally, as gout is associated with increased cardiovascular disease (CVD) risk, changes in CVD risk markers, including blood pressure, arterial stiffness and cholesterol levels, will also be assessed. Participants will be recruited through the use of posters, advertising on the UK Gout Society website, emails to large organisations and through letters sent from General Practitioners' (GP) surgeries to eligible patients. Potentially eligible patients will be identified by surgery staff using their patient database before contact information is passed to the research team at the surgery to prepare and send out invitation letters. As this method of recruitment involves accessing patient identifiable data (name and home address) prior to patient consent being given, an application to the Confidentiality Advisory Group (CAG) will be submitted for consideration. A general linear mixed model analysis will be used to assess the effect of treatment allocation, time and their interaction on both primary and secondary outcome measures.

Official Title
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The Effect of Tart Cherry Juice on Risk of Gout Attacks: a Randomised Controlled Trial

Conditions
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Gout Flare, Gout Attack

Intervention / Treatment
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* Dietary Supplement: Tart cherry juice
* Other: Fruit-flavoured placebo drink


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: existing diagnosis of gout have experienced at least one gout flare in the previous 12 months able and willing to participate in the study and provide written informed consent Exclusion Criteria: frequently consume cherries or cherry products e.g. cherry supplements and juice (more than once a week) severe renal impairment (estimated glomerular filtration rate of <30ml/min)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly allocated to consume either tart cherry juice or a fruit-flavoured placebo drink (matched as closely as possible for energy and sensory characteristics) daily for 12 months.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tart cherry juice<br>30 mL tart cherry concentrate (CherryActive, UK) diluted with 220 mL of water once per day (250 mL total volume per day). According to available manufacturers data, this is equivalent to consuming 90-100 fresh cherries per day. | Dietary Supplement: Tart cherry juice<br>* 30 mL tart cherry juice concentrate (CherryActive, UK), diluted with water to 250 mL. This is consumed daily by participants, with breakfast, for 12 months.<br>|
| Placebo Comparator: Fruit-flavoured placebo drink<br>Matched for sensory characteristics and energy (with the addition of glucose). once per day (250 mL total volume per day) | Other: Fruit-flavoured placebo drink<br>* Consumed daily by participants, with breakfast, for 12 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gout flare frequency | Difference in gout flare frequency in tart cherry juice group versus placebo group from baseline to 12 months. Recorded as number per month. | Measured at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in gout flare intensity | Difference in gout flare intensity in tart cherry juice group versus placebo group from baseline to 12 months. Using a 0-10 Likert pain scale. The scale measures the pain of any gout flare. The possible score ranges from 0 for no pain through to 10 for worst pain imaginable. Change in pain scores between treatment and placebo groups will be compared throughout the duration of the intervention. | Measured at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months | 
| Changes in serum urate (in millimoles per litre (mmol/l)) | Difference in serum urate in tart cherry juice group versus placebo group from baseline to 12 months. | Measured at 0, 6 and 12 months | 
| Change in fractional excretion of uric acid (as a percentage, %) | Difference in fractional excretion of uric acid in tart cherry juice group versus placebo group from baseline to 12 months. Measured from 24 hour urine sample. | Measured at 0, 6 and 12 months | 
| Change in inflammatory markers (in milligrams per litre (mg/l)) | Difference in inflammatory markers (c reactive protein (CRP), inter leukin-6 (IL-6) and tumour necrosis factor- alpha (TNF-alpha)) in tart cherry juice group versus placebo group from baseline to 12 months. Measured using an enzyme-linked immunosorbent assay (ELISA). | Measured at 0, 6 and 12 months | 
| Change in oxidative damage (in percentage (%) of tail DNA) | Difference in markers of oxidative stress in tart cherry juice group versus placebo group from baseline to 12 months. Measured using single-cell electrophoresis 'comet assay' as 8-oxo-dg levels in lymphocytes. | Measured at 0, 6 and 12 months | 
| Change in antioxidant status (in percentage (%) of tail DNA) | Difference in antioxidant status in tart cherry juice group versus placebo group from baseline to 12 months. Measured using single-cell electrophoresis 'comet assay' as resistance of DNA lymphocyte to H202-induced DNA strand breaks. | Measured at 0, 6 and 12 months | 
| Change in blood pressure (in millimetres of mercury (mmHg)) | Difference in brachial and central blood pressure in tart cherry juice group versus placebo group from baseline to 12 months. Measured using a Vicorder. | Measured at 0, 6 and 12 months | 
| Change in arterial stiffness (in meters per second (m/s)) | Difference in arterial stiffness in tart cherry juice group versus placebo group from baseline to 12 months. | Measured at 0, 6 and 12 months | 
| Change in lipid profile (in millimoles per litre (mmol/l)) | Difference in total cholesterol, HDL cholesterol, LDL cholesterol and triacylglycerides) in tart cherry juice group versus placebo group from baseline to 12 months. | Measured at 0, 6 and 12 months | 
| Height (in meters (m)) | Height and weight will be combined to report BMI in kg/m^2. Difference in BMI in tart cherry juice group versus placebo group from baseline to 12 months. | Measured at 0, 6 and 12 months | 
| Weight (in kilograms (kg)) | Height and weight will be combined to report BMI in kg/m^2. Difference in BMI in tart cherry juice group versus placebo group from baseline to 12 months. | Measured at 0, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tart cherries, gout, cardiovascular disease risk, gout attack, gout flare