The Effect of Tart Cherry Juice on Risk of Gout Attacks

Sponsor

Sheffield Hallam University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03621215

Collaborator

Cherry Research Committee (Other)

120

Enrollment

Location

Arms

20.6

Anticipated Duration (Months)

5.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Gout Flare Gout Attack	Dietary Supplement: Tart cherry juice Other: Fruit-flavoured placebo drink	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 15, 2019

Anticipated Primary Completion Date :

Mar 1, 2021

Anticipated Study Completion Date :

Apr 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tart cherry juice 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 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.
Placebo Comparator: Fruit-flavoured placebo drink 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 Consumed daily by participants, with breakfast, for 12 months.

Arm

Intervention/Treatment

Experimental: Tart cherry juice

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

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.

Placebo Comparator: Fruit-flavoured placebo drink

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

Consumed daily by participants, with breakfast, for 12 months.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in gout flare intensity [Measured at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months]
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.
Changes in serum urate (in millimoles per litre (mmol/l)) [Measured at 0, 6 and 12 months]
Difference in serum urate in tart cherry juice group versus placebo group from baseline to 12 months.
Change in fractional excretion of uric acid (as a percentage, %) [Measured at 0, 6 and 12 months]
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.
Change in inflammatory markers (in milligrams per litre (mg/l)) [Measured at 0, 6 and 12 months]
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).
Change in oxidative damage (in percentage (%) of tail DNA) [Measured at 0, 6 and 12 months]
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.
Change in antioxidant status (in percentage (%) of tail DNA) [Measured at 0, 6 and 12 months]
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.
Change in blood pressure (in millimetres of mercury (mmHg)) [Measured at 0, 6 and 12 months]
Difference in brachial and central blood pressure in tart cherry juice group versus placebo group from baseline to 12 months. Measured using a Vicorder.
Change in arterial stiffness (in meters per second (m/s)) [Measured at 0, 6 and 12 months]
Difference in arterial stiffness in tart cherry juice group versus placebo group from baseline to 12 months.
Change in lipid profile (in millimoles per litre (mmol/l)) [Measured at 0, 6 and 12 months]
Difference in total cholesterol, HDL cholesterol, LDL cholesterol and triacylglycerides) in tart cherry juice group versus placebo group from baseline to 12 months.
Height (in meters (m)) [Measured at 0, 6 and 12 months]
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.
Weight (in kilograms (kg)) [Measured at 0, 6 and 12 months]
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.

Other Outcome Measures

Changes in habitual diet [Measured at 0, 6 and 12 months]
4 day diet diaries will be used to assess any changes in habitual diet as a result of, or over the course of, the study.
Changes in habitual physical activity levels [Measured at 0, 6 and 12 months]
4 day physical activity logs will be used to assess any changes in habitual activity levels as a result of, or over the course of, the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)