Clinical trial NCT04960527: Acute Effects of Tart Cherry on Uric Acid and Biomarkers of CVD Risk in Healthy Individuals
Official title: The Acute Effects of Tart Cherry Juice on Uric Acid and Biomarkers of Cardiovascular Disease Risk in Healthy Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Uric Acid
Cardiovascular Diseases
Gout
Lead sponsor: Sheffield Hallam University
Sponsor class: OTHER
First posted: 2021-07-14
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: 2-way crossover, randomised controlled trial. Participants will be allocated to consume tart cherry juice or a neutral water control on separate occasions. The order of this allocation will be randomised.
Primary purpose: PREVENTION

Brief summary: This study aims to provide evidence as to whether consumption of tart cherry juice can reduce the risk of gout and cardiovascular disease (CVD) in an acute context. The proposed study is a 2-way cross-over, randomised, placebo-controlled trial and aims to answer the following research questions:

1. What effect does a single 30mL serving of tart cherry concentrate have on serum uric acid and urinary excretion of uric acid in healthy individuals, when compared with water?
2. What effect does a single 30mL serving of tart cherry concentrate have on markers of cardiovascular disease risk and oxidative stress in healthy individuals, when compared with water?

By measuring acute changes in serum urate, fractional urinary urate excretion, inflammatory markers, oxidative stress markers and CVD risk markers (namely central and brachial blood pressure, and arterial stiffness), it will highlight possible mechanisms through which tart cherry may reduce risk of gout and/or CVD.

Detailed description: Healthy, non-smoking, adult volunteers (n = 15) will be recruited to a 2-way cross-over, randomized, placebo-controlled study.

A sample size of 13 has been calculated using data from White et al. (2018), using the primary outcome of change in serum uric acid level. Between-person variations in serum urate was established at approximately 50 µmol/L. Within-subject variation to apple juice was approximately 35 µmol/L. It has been estimated that cherry juice will produce a fall in serum urate of approximately 15 µmol/L (Jacob et al., 2003). Therefore, 13 participants will be needed to detect this change with 80% power at an alpha level of 0.05.

Participants will avoid strenuous exercise for 72-hours prior to the study until 24-hours post-consumption of the test drinks; compliance will be assessed through completion of a physical activity diary. They will also follow a low-polyphenolic diet for 48-hours prior to the study until 24-hours post-consumption of the test drinks; participants will be provided with a list of foods/drinks to avoid and compliance will be assessed through completion of a food diary. Participants will be provided with instructions of foods to avoid and a low polyphenolic pasta ready-meal, dessert and low nitrate water to consume the evening preceding the study day.

Participants will attend the laboratory following an overnight fast. Blood pressure (central and brachial) and arterial stiffness will be measured using a non-invasive Vicorder device. A venepuncture blood sample will be collected by a researcher trained in phlebotomy before consumption of the test drink. Approximately 10 ml of blood will be taken during each venepuncture. A urine sample will also be collected. Participants will consume 250 ml of tart cherry juice or neutral control (water) on two occasions, at least one week apart; the sequence order will be random. The cherry juice comprises 30 mL tart cherry concentrate diluted with 220 mL water. Further venous blood samples will be taken at 1 and 2 hours post-consumption. These will be supplemented with finger-prick samples collected at 3, 5 and 24 hours post drink. Post-drink measures of arterial stiffness will be taken at 1, 2, 3, 5 and 24-hours post-consumption. Additional urine samples will also be collected between 0-2, 2-4, 4-5, 5-8, 8-11, and 11-24 hours, post-consumption of the test drinks. Participants' water intake during each laboratory visit will be standardised at 500 ml. Participants will be provided with a low-polyphenolic sandwich lunch, pasta ready-meal dinner, dessert, snacks and low nitrate water to consume following the 5-hour measurements. Participants will return to the laboratory the next morning following a 12-hour fast for their 24-hour measurements.

Blood will be analysed for serum uric acid and creatinine concentrations at all time points and for CRP (a measure of inflammation) at baseline, 2, and 5 hours, post-drink. White blood cells (lymphocytes) will be separated from whole venous blood samples collected at baseline, 1 and 2-hours post-drink consumption for the analysis of oxidative DNA damage. Urine samples will be analysed for uric acid and creatinine to calculate fractional excretion of urinary uric acid (using a commercial colorimetric assay). Polyphenolic metabolites from the test drink will also be analysed in urine samples.

Data analysis: The effect of the treatment (tart cherry versus water) on all outcome variables will be analysed with 2-way repeated measures ANOVAs. A statistical significance level of P≤ 0.05 will be set.

Eligibility criteria: Inclusion Criteria:

* aged 18 years or over
* able and willing to participate in the study and provide written informed consent

Exclusion Criteria:

* current smoker
* any known food allergies/intolerances
* history of medical conditions, including gastrointestinal disease, severe renal impairment (estimated glomerular filtration rate of \<30ml/min) or renal disease, cardiovascular disease, diabetes (type 1 or type 2) and gout

Primary outcomes:
measure: Change in serum urate (in millimoles per litre (mmol/l)
timeFrame: Measured at baseline, 1, 2, 3, 5 and 24 hours post-consumption of test drink
Secondary outcomes:
measure: Change in urinary urate (mmol/l)
timeFrame: Measured from samples collected at baseline and between 0-2 hours, 2-4 hours, 4-5 hours, 5-8 hours, 8-11 hours and 11-24 hours
measure: Change in urinary creatinine (mmol/l)
timeFrame: Measured from samples collected at baseline and between 0-2 hours, 2-4 hours, 4-5 hours, 5-8 hours, 8-11 hours and 11-24 hours
measure: Change in serum creatinine (mmol/l)
timeFrame: Measured at baseline, 1, 2, 3, 5 and 24 hours post-consumption of test drink
measure: Change in c reactive protein (in milligrams per litre (mg/l)
timeFrame: Measured at baseline, 2 and 5 hours post-consumption of test drink
measure: Change in blood pressure (in millimetres of mercury (mmHg))
timeFrame: Measured at baseline, 1, 2, 3, 5, and 24-hours post-consumption of test drink
measure: Change in arterial stiffness (Augmentation index measured in %, pulse wave velocity measured in meters per second (m/s))
timeFrame: Measured at baseline, 1, 2, 3, 5, and 24-hours post-consumption of test drink
measure: Change in oxidative damage (in percentage (%) of tail DNA)
timeFrame: Measured at baseline, 1 and 2 hours post-consumption of test drink
Other outcomes:
measure: Avoidance of strenuous physical activity
timeFrame: Measured from 72-hours prior to the study until 24-hours post-consumption of test drink
measure: Adherence to a low-polyphenolic diet
timeFrame: Measured from 48-hours prior to the study until 24-hours post-consumption of test drink
Locations:
city: Sheffield
country: United Kingdom
facility: Food and Nutrition Group, Sheffield Hallam University
Study officials:
affiliation: Sheffield Hallam University
name: Tony Lynn, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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: White SJ, Carran EL, Reynolds AN, Haszard JJ, Venn BJ. The effects of apples and apple juice on acute plasma uric acid concentration: a randomized controlled trial. Am J Clin Nutr. 2018 Feb 1;107(2):165-172. doi: 10.1093/ajcn/nqx059.
citation: Lynn A, Mathew S, Moore CT, Russell J, Robinson E, Soumpasi V, Barker ME. Effect of a tart cherry juice supplement on arterial stiffness and inflammation in healthy adults: a randomised controlled trial. Plant Foods Hum Nutr. 2014 Jun;69(2):122-7. doi: 10.1007/s11130-014-0409-x.
citation: Chai SC , Davis K , Wright RS , Kuczmarski MF , Zhang Z . Impact of tart cherry juice on systolic blood pressure and low-density lipoprotein cholesterol in older adults: a randomized controlled trial. Food Funct. 2018 Jun 20;9(6):3185-3194. doi: 10.1039/c8fo00468d.
citation: Bell, P. G., Gaze, D. C., Davison, G. W., George, T. W., Scotter, M. J., & Howatson, G. (2014). Montmorency tart cherry (Prunus cerasus L.) concentrate lowers uric acid, independent of plasma cyanidin-3-O-glucosiderutinoside. Journal of Functional Foods, 11, 82-90.