Clinical trial NCT01923597: Effect of Green Tea (Epigallocatechin Gallate) on Albuminuria in Patients With Diabetic Nephropathy.
Official title: A Randomized, Placebo-controlled, Parallel-group Study to Evaluate the Effect of Green Tea on Albuminuria in Patients With Diabetic Nephropathy and Use of Maximum Dose of ACE-I and / or Angiotensin II Receptor Blocker.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathy
Hypertension
Keywords: Proteinuria
Oxidative stress
Epigallocatechin gallate
Lead sponsor: University of Campinas, Brazil
Sponsor class: OTHER
First posted: 2013-08-15
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effect of green tea (epigallocatechin gallate) in albuminuria in diabetic patients and nephropathy.

Detailed description: Clinical, prospective, randomized, double-blind, placebo-controlled, with analysis by intention to treat.

50 individuals will be selected with a diagnosis of diabetes / hypertension and has been followed in Diabetic Nephropathy Clinic of the Faculty of Medical Sciences, University of Campinas (UNICAMP). Participants are divided into 02 groups: 1) 25 patients treated with maximum dose of ACE-I and / or angiotensin II receptor blocker (ARBs) + Placebo (absence of epigallocatechin gallate) and 2) treated 25 patients with maximum dose of ACE-I and / or ARBs + green tea (epigallocatechin gallate).

The patients will receive four capsules Polyphenol E - epigallocatechin gallate (Polyphenon Pharma, NY) per day, corresponding to 800 mg of epigallocatechin gallate (EGCG), or placebo (no epigallocatechin gallate) for 3 months. Patients will not be aware of the treatment they are receiving. The subjects will be allocated for the treatment or placebo, stratified by sex. To avoid the influence of researchers, the randomization list will be generated and maintained by trained personnel in a different location from the study. Before treatment and immediately after 3 months of treatment will be obtained in the primary outcome measures (albuminuria) and secondary (plasma metabolites of flavonoids, level of urinary F2-isoprostane and 8-hydroxydeoxyguanosine). In these same times will be obtained: blood biochemistry (glucose, glycosylated hemoglobin, urea, creatinine, sodium, potassium, blood count, calcium, phosphorus, cholesterol, LDL, HDL, triglycerides, uric acid), 3 samples of first morning urine to determine albuminuria, glomerular filtration rate (GFR), blood pressure measurement of 24 h, physical examination, weight, blood pressure and heart rate. Adherence to the study will be evaluated by weekly phone and the expected increase in plasma of flavonoids using the green tea (epigallocatechin gallate). The antihypertensive drug may be adjusted to obtain the desired pressure (\<130/80 mmHg).

Eligibility criteria: Inclusion Criteria:

* 18 years or more
* prior diagnosis of diabetes mellitus (DM)
* persistent micro-or macroalbuminuria (urinary albumin excretion\> 30 mg / g creatinine (AUC) in 3 consecutive measurements on different days)
* glycated hemoglobin \<10%
* maximum dose of ACE-I and / or ARBs.

Exclusion Criteria:

* diagnosis of autoimmune diseases, HIV, hepatitis, cancer, inflammatory disease
* pregnant or lactating patients
* glomerular filtration rate (GFR) \<30 ml/min/1, 73m2 (estimated by the MDRD and the Cockcroft-Gault formula)
* presence of kidney disease unrelated to diabetes
* chronic urinary tract infection
* diagnosis of congestive heart failure (CHF) New York Heart Association (NYHA) class III or IV
* recent history (\<6 months) unstable angina, myocardial infarction, stroke, coronary intervention
* history of alcohol and / or drugs
* mental incapacity to understand the informed consent
* intolerance to green tea

Primary outcomes:
measure: Effect of green tea (epigallocatechin gallate) in albuminuria in diabetic patients and nephropathy.
timeFrame: After 3 months of treatment
Secondary outcomes:
measure: Effect of green tea (epigallocatechin gallate) on oxidative stress in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
measure: Effect of green tea (epigallocatechin gallate) on blood glucose control in patients with diabetic nephropathy.
timeFrame: After 3 months of tretatment
measure: Effect of green tea (epigallocatechin gallate) on blood pressure in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
measure: Effect of green tea (epigallocatechin gallate) on plasma lipids in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
measure: Effect of green tea (epigallocatechin gallate) on plasma metabolites of flavonoids in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
measure: Effect of green tea (epigallocatechin gallate) on plasma lipids in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
measure: Effect of green tea (epigallocatechin gallate) on plasma lipids in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
Other outcomes:
measure: Effect of Green Tea (epigallocatechin gallate) in the glomerular filtration rate in patients with diabetic nephropathy.
timeFrame: After 3 months of treatment
Locations:
city: Campinas
country: Brazil
facility: Unicamp
state: São Paulo
Study officials:
affiliation: University of Campinas, Brazil
name: José B. Lopes de Faria, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Faria AM, Papadimitriou A, Silva KC, Lopes de Faria JM, Lopes de Faria JB. Uncoupling endothelial nitric oxide synthase is ameliorated by green tea in experimental diabetes by re-establishing tetrahydrobiopterin levels. Diabetes. 2012 Jul;61(7):1838-47. doi: 10.2337/db11-1241. Epub 2012 May 14.
citation: Ribaldo PD, Souza DS, Biswas SK, Block K, Lopes de Faria JM, Lopes de Faria JB. Green tea (Camellia sinensis) attenuates nephropathy by downregulating Nox4 NADPH oxidase in diabetic spontaneously hypertensive rats. J Nutr. 2009 Jan;139(1):96-100. doi: 10.3945/jn.108.095018. Epub 2008 Dec 3.
citation: Borges CM, Papadimitriou A, Duarte DA, Lopes de Faria JM, Lopes de Faria JB. The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial. Sci Rep. 2016 Jun 20;6:28282. doi: 10.1038/srep28282.