Clinical trial NCT03621215: The Effect of Tart Cherry Juice on Risk of Gout Attacks
Official title: The Effect of Tart Cherry Juice on Risk of Gout Attacks: a Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Gout Flare
Gout Attack
Keywords: tart cherries
gout
cardiovascular disease risk
gout attack
gout flare
Lead sponsor: Sheffield Hallam University
Sponsor class: OTHER
Collaborators: name: Cherry Research Committee
First posted: 2018-08-08
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in gout flare frequency
timeFrame: Measured at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months
Secondary outcomes:
measure: Change in gout flare intensity
timeFrame: Measured at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 months
measure: Changes in serum urate (in millimoles per litre (mmol/l))
timeFrame: Measured at 0, 6 and 12 months
measure: Change in fractional excretion of uric acid (as a percentage, %)
timeFrame: Measured at 0, 6 and 12 months
measure: Change in inflammatory markers (in milligrams per litre (mg/l))
timeFrame: Measured at 0, 6 and 12 months
measure: Change in oxidative damage (in percentage (%) of tail DNA)
timeFrame: Measured at 0, 6 and 12 months
measure: Change in antioxidant status (in percentage (%) of tail DNA)
timeFrame: Measured at 0, 6 and 12 months
measure: Change in blood pressure (in millimetres of mercury (mmHg))
timeFrame: Measured at 0, 6 and 12 months
measure: Change in arterial stiffness (in meters per second (m/s))
timeFrame: Measured at 0, 6 and 12 months
measure: Change in lipid profile (in millimoles per litre (mmol/l))
timeFrame: Measured at 0, 6 and 12 months
measure: Height (in meters (m))
timeFrame: Measured at 0, 6 and 12 months
measure: Weight (in kilograms (kg))
timeFrame: Measured at 0, 6 and 12 months
Other outcomes:
measure: Changes in habitual diet
timeFrame: Measured at 0, 6 and 12 months
measure: Changes in habitual physical activity levels
timeFrame: Measured at 0, 6 and 12 months
Locations:
city: Sheffield
country: United Kingdom
facility: Food and Nutrition Group, Sheffield Hallam University
Study officials:
affiliation: Sheffield Hallam University
name: Margo Barker
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum. 2012 Dec;64(12):4004-11. doi: 10.1002/art.34677.
citation: Jacob RA, Spinozzi GM, Simon VA, Kelley DS, Prior RL, Hess-Pierce B, Kader AA. Consumption of cherries lowers plasma urate in healthy women. J Nutr. 2003 Jun;133(6):1826-9. doi: 10.1093/jn/133.6.1826.
citation: Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study. Ann Rheum Dis. 2015 Apr;74(4):661-7. doi: 10.1136/annrheumdis-2013-204463. Epub 2014 Jan 15.
citation: Cea Soriano L, Rothenbacher D, Choi HK, Garcia Rodriguez LA. Contemporary epidemiology of gout in the UK general population. Arthritis Res Ther. 2011 Mar 3;13(2):R39. doi: 10.1186/ar3272.
citation: Rothenbacher D, Primatesta P, Ferreira A, Cea-Soriano L, Rodriguez LA. Frequency and risk factors of gout flares in a large population-based cohort of incident gout. Rheumatology (Oxford). 2011 May;50(5):973-81. doi: 10.1093/rheumatology/keq363. Epub 2011 Jan 12.
citation: Dalbeth N, Ames R, Gamble GD, Horne A, Wong S, Kuhn-Sherlock B, MacGibbon A, McQueen FM, Reid IR, Palmano K. Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares: a proof-of-concept randomised controlled trial. Ann Rheum Dis. 2012 Jun;71(6):929-34. doi: 10.1136/annrheumdis-2011-200156. Epub 2012 Jan 23.
citation: Lamb KL, Lynn A, Russell J, Barker ME. Effect of tart cherry juice on risk of gout attacks: protocol for a randomised controlled trial. BMJ Open. 2020 Mar 15;10(3):e035108. doi: 10.1136/bmjopen-2019-035108.