Effects of Cranberry Supplementation on Chronic Kidney Disease Patients.

Study Overview
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Brief Summary
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Patients with chronic kidney disease (CKD) have several complications that are linked to oxidative stress and inflammation, and among the most recently studied is the alteration of the intestinal microbiota. Considering this scenario, bioactive compounds have been considered as a therapeutic alternative in the modulation of intestinal microbiota as well as transcription factors such as nuclear-kappa factor B (NF-κB) and factor 2 nuclear factor-related erythroid 2 Nrf2), involved with oxidative stress and inflammation. Among several foods, cranberry is a fruit rich in flavonoids and other polyphenols, which has antioxidant, anti-inflammatory and immunoregulatory actions and may be an adjuvant treatment for CKD complications. However, clinical evidence evaluating the effects of cranberry is limited and there are no studies specifically involving patients with CKD. Thus, the present randomized crossover double-blind crossover with placebo-controlled washout period will aim to evaluate the effects of cranberry supplementation on the modulation of the intestinal microbiota and expression of transcription factors as well as cytokine levels inflammatory effects of CKD patients.

Detailed Description
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This is a longitudinal study with a randomized crossover design, double-blind, placebo-controlled, and with washout period. Thirty non-dialysis patients of both genders, aged between 18 and 60 years and with CKD stage3-4 (glomerular filtration rate < 59 mL/min/1.73 m2) will be included in the study. Pregnant patients, smokers and those under use of antibiotics in the last 3 months, or in use antithrombotic, pre-, pro- or synbiotic supplements, antioxidant supplements or habitual cranberry intake will be excluded. In addition, those with autoimmune and infectious diseases, cancer, liver diseases and HIV will also not be included in the study. The patients that fulfill the eligible criteria and sign the ethical informed consent will be randomized to either Group A (Cranberry) or Group B (Placebo). During 12 weeks, patients allocated in group A will receive capsules containing cranberry extract (Vaccinium macrocarpon to 25% anthocyanosides 160mg, equivalent to 40mg anthocyanosides), once daily (lunch), totaling 500mg / day and those allocated in the group B will receive a placebo (500mg of corn starch). After the supplementation period, a 12-week washout will be performed for subsequent crossover of the supplement. The randomization will be computed in the ratio of 1: 1, with block size of 15 (Cranberry group and Control), to receive cranberry or placebo. This project was approved by the Ethics Committee of the Faculty of Medicine-UFF, n. 2.653.752.

Official Title
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Effects of Cranberry Supplementation on Chronic Kidney Disease Patients.

Conditions
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Renal Insufficiency, Chronic, Inflammation, Oxidative Stress, Gastrointestinal Microbiome

Intervention / Treatment
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* Dietary Supplement: Cranberry
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of Chronic Kidney Disease in conservative treatment Aged 18 years or older Must be able to swallow tablets Exclusion Criteria: Patients pregnant Smokers Using antibiotics in the last 3 months Using antioxidant supplements in the last 3 months Usual intake of cranberry fruit or extract Clinical diagnosis of infectious diseases Clinical diagnosis of Cancer Clinical diagnosis of AIDS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cranberry<br>Administration of 2 capsules with 500mg (Miralys Ltda) of cranberry extract per day, for 8 weeks | Dietary Supplement: Cranberry<br>* The patients will receive 2 capsules per day containing 500mg of cranberry extract for 8 weeks<br>|
| Placebo Comparator: Placebo<br>Administration of 2 capsules with 500mg of maize starch per day, for 8 weeks | Dietary Supplement: Placebo<br>* The patients will receive 2 capsules per day containing 500mg of maize starch for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antioxidants and anti-inflammatory biomarkers | Evaluate the supplementation effects in anti-inflammatory biomarkers- Nrf2 and antioxidants enzymes | 3 months | 
| Inflammatory biomarkers | Evaluate the supplementation effects in inflammatory biomarkers- factor nuclear kappa B (NFkB), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) | 3 months | 
| Biochemical Routine | Urea, creatinine, albumin, lipid profile plasma levels | 12 weeks | 
| Uremic toxins | P-cresol, indoxyl sulfate plasma levels | 6 months |