Clinical trial NCT01562340: Pomegranate and Hemodialysis Pilot Trial
Official title: A Pilot Trial Assessing the Effect of Pomegranate Juice and Extract on Biomarkers of Oxidative Stress, Systemic Inflammation, and Monocyte Function in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End Stage Renal Disease
Cardiovascular Disease
Inflammation
Keywords: Hemodialysis
End stage renal disease
Oxidative stress
Inflammation
Endothelial dysfunction
Cardiovascular disease
Antioxidants
Flavonoids
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2012-03-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: In this study, the investigators will administer pomegranate juice or fruit extract as a targeted antioxidant therapy to hemodialysis patients.

The investigators will examine whether these pomegranate products will be safe and well-tolerated. The investigators will also examine whether these products may lead to improvements in blood serum biomarkers of:

* oxidative stress status
* inflammatory status
* endothelial dysfunction

Detailed description: There are currently more than 400,000 patients receiving chronic dialysis therapy in the United States. Cardiovascular and infectious diseases are the leading causes of death in hemodialysis patients, accounting for over 50% of all-cause mortality.

There is a complex interaction of inflammation, oxidative stress, and endothelial dysfunction in contributing to cardiovascular and infectious risk in dialysis patients. Since there is much evidence that an increase in oxidative stress contributes to risk of disease in dialysis patients, it is logical to hypothesize the antioxidant therapy may be beneficial in reducing these risks.

In addition to vitamins C and E, the most common and active antioxidant compounds that occur naturally in foods are flavonoids. Dietary flavonoids are highly bioavailable, and have been shown to confer antioxidant protection, inhibit platelet activation, exert vasorelaxant effects, and reduce inflammation in human studies. In animal model studies, dietary flavonoids have been shown to reduce the development of atherosclerosis. Polyphenols also have potent antibacterial, antifungal, and antiviral activities.

Pomegranate juice is a rich source of potent phenolic antioxidants, which have been demonstrated to have anti-atherogenic and vasorelaxant properties. Pomegranate derived polyphenols have also been demonstrated to inhibit platelet activation.

Although available data are limited, several studies suggest that dietary phenols may have beneficial effects in patients undergoing dialysis treatment. These include improvements in lipoprotein profiles, reductions in circulating inflammatory and oxidative stress biomarkers, reductions in infectious complications, and improvements in inflammatory biomarkers. These observations, though limited, suggest that polyphenol based supplementation strategies may be effective in reducing complications in those undergoing dialysis treatment.

In this study, the investigators will administer pomegranate juice and/or fruit extract as a targeted antioxidant therapy. The investigators will examine whether these pomegranate products will be safe and well-tolerated. The investigators will also examine whether these products may lead to improvements in biomarkers of oxidative stress status, inflammatory status, and endothelial dysfunction in hemodialysis patients.

Eligibility criteria: Inclusion Criteria:

* Patients with end-stage renal disease receiving thrice weekly hemodialysis
* Age \> 18 or \< 85 years
* Life expectancy greater than one year
* Ability to understand and provide informed consent for participation in the study

Exclusion Criteria:

* History of poor adherence to hemodialysis or medical regimen
* Prisoners, patients with significant mental illness, and other vulnerable populations
* AIDS (HIV seropositivity is not an exclusion criteria)
* Active malignancy excluding basal cell carcinoma of the skin
* Gastrointestinal dysfunction requiring parenteral nutrition
* History of functional kidney transplant \< 6 months prior to study entry
* Anticipated live donor kidney transplant
* Patients taking vitamin E supplements \> 60 IU/day, vitamin C \> 150 mg/day or other antioxidant or nutritional supplements
* Incident hemodialysis patients (defined as within 30 days of dialysis initiation)
* Patients hospitalized for more than 5 days within the past 30 days.
* Patients with a history of a major atherosclerotic event (defined as combined incidence of myocardial infarction, urgent target-vessel revascularization, coronary bypass surgery, and stroke) within three months
* Pregnancy

Primary outcomes:
measure: Markers of oxidative stress
timeFrame: 12 weeks
measure: Markers of inflammation
timeFrame: 12 weeks
measure: Markers of endothelial function
timeFrame: 12 weeks
Secondary outcomes:
measure: Number of subjects with adverse events and type of event
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Northwest Kidney Centers
state: Washington
Study officials:
affiliation: University of Washington
name: Jonathan Himmelfarb, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rivara MB, Mehrotra R, Linke L, Ruzinski J, Ikizler TA, Himmelfarb J. A pilot randomized crossover trial assessing the safety and short-term effects of pomegranate supplementation in hemodialysis patients. J Ren Nutr. 2015 Jan;25(1):40-9. doi: 10.1053/j.jrn.2014.07.006. Epub 2014 Sep 11.