Green Tea Extract on Soluble RAGE in Patients With Diabetic Nephropathy

Diabetic Nephropathy Type 2 Clinical Trial

Official title:

Effect of the Administration of Green Tea Extract on Soluble RAGE and Kidney Disease in Patients With Diabetes Mellitus Type 2

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03622762
• Other study ID #: CUCS-INTEC-MV-ERVE-06
• Status: Recruiting
• Phase: Phase 2
• Start date: July 15, 2018
• Est. completion date: June 20, 2019

Study information

• Verified date: February 2019
• Source: Centro Universitario de Ciencias de la Salud, Mexico
• Contact: Fernando Grover Páez, PhD
• Phone: (33) 10585200
• Email: fgroverp[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Diabetic nephropathy is one of the most feared complications of Diabetes Mellitus type 2, characterized mainly by the decrease in the glomerular filtration rate and an increase in protein secretion by the kidney, that results in proteinuria. This has led to the development of intensive treatment regimens for patients with diabetes and preventive measures since once the complications have already presented the improvement of glycemic control alone may not be enough, to prevent the progression of pathological processes. Currently, interventions to delay the progression of kidney damage, include changes in lifestyle, nutritional advice and regular exercise, achieve optimal levels in glycemic control and use of pharmacological therapies with nephroprotector, angiotensin II receptor blocker (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs). The most important biochemical mechanism proposed for this progression is the excessive binding of glucose to proteins, better described as the final products of advanced glycosylation (AGEs); the interaction of AGEs with its receptor (RAGE), participates in the metabolic and biochemical pathways in intracellular signaling, either by favoring or aggravating cell nephron damage. Recently, numerous RAGE isoforms have been described as: soluble RAGE, which are devoid of cytoplasmic domains, which bind to ligands that include AGEs and can antagonize intracellular signaling. Therefore, the need to seek for alternative therapies like nutraceuticals is arising, mainly due to its low toxicity and lower cost. Such is the case of green tea extract, which due to its chemical composition, especially of flavonoids that generate antioxidant and anti-inflammatory effects, In vivo and in clinical trials have shown that it could impact the progression of the diabetic neuropathy , through the modulation of the biological process, including molecular and biochemical pathways such as release of soluble RAGE.

Description:

The objective of the study is to evaluate the effect of the administration of green tea extract on soluble RAGE and renal damage in patients with Type 2 Diabetes Mellitus, by means of a clinical trial, double blind, with randomization and placebo control group. In male and female population, with a diagnosis of Diabetes Mellitus type 2, under treatment with hypoglycemic agents and / or insulin and kidney damage, 2 - 3a grade according to classification of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and HbA1c levels 9 - 12% who sign the letter of consent under information, from 35 to 65 years of age, residents of the metropolitan area of Guadalajara.

All patients who meet the selection criteria and who sign their informed consent will be given the clinical history, as well as anthropometric and laboratory determinations. Once these values are known, the intervention will proceed with the research product, extract of green tea 400 mg twice a day or placebo 400 mg twice a day, this will be according to the technique of masking by the closed envelope technique for 12 weeks. Patients will be evaluated at 30, 60 and 90 days of intervention, for attachment assessment, tolerability of treatment, side effects and laboratory safety determinations. At the end of the 12 weeks of the intervention, the anthropometric and laboratory determinations will be made again as well as the determination of soluble RAGE by means of Elisa sandwich type, in serum obtained at the beginning and at 12 weeks of intervention.

The database will be developed in the statistical program Statistical software (SPSS) version 21.0. The qualitative variables will be expressed in frequencies and percentages, while the quantitative variables will be expressed in means and standard deviations, the normality test will be carried out through the Kolmogorov-Smirnov test and, according to the result, it will be decided for the analysis intra group perform paired t or Wilcoxon method and for intergroup t student or Mann-Whitney U. A value of p ≤0.05 will be considered statistically significant.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 20, 2019
• Est. primary completion date: March 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

• People of both sexes

• Age from 40 to 65 years

• Signature of consent under information

• Diagnosis of type 2 diabetes mellituswith stable pharmacological treatment

• Glomerular filtration rate between 89 - 45 ml / min / 1.73 m2

• Albumin / creatinine ratio = 30 - 300 mg / min

• HbA1c levels 7 - 12%

• Body mass index - 34.9

Exclusion Criteria:

• Glomerular filtration rat lower than 44 ml / min / 1.73 m2

• Albumin / creatinine ratio = 300

• Other causes of kidney disease

• Other types of Diabetes

• Liver, thyroid or heart diseases

• Intolerance related to green tea or placebo components

• Use of antioxidant supplements

• Active alcoholism

• Patients with pregnancy or without a safe contraceptive method

• Patients in breastfeeding period

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy Type 2
• Kidney Diseases

Intervention

Drug:
• green tea extract
Capsules of green tea extract, 400 mg twice a day, fasting
• Placebo
Placebo capsules, 400 mg twice daily fasting

Locations

Country	Name	City	State
Mexico	Institute of Experimental and Clinical Therapeutics (INTEC), CUCS, University of Guadalajara	Guadalajara	Jalisco

Sponsors (1)

Lead Sponsor	Collaborator
Centro Universitario de Ciencias de la Salud, Mexico

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Total cholesterol	Before and after intervention by spectrophotometry	90 days
Other	triglycerides	Before and after intervention by spectrophotometry	90 days
Other	High-density lipoprotein cholesterol	Before and after intervention by spectrophotometry	90 days
Other	Low-density lipoprotein cholesterol	Before and after intervention by friedewall formula	90 days
Other	Weight and visceral fat %	Before and after intervention using a vascula of impedance	90 days
Primary	Soluble RAGE concentration	Before and after the intervention using the serum extracted from the patient using sandwich ELISA.	90 days
Secondary	Glomerular filtration rate	Before and after the intervention, it will be evaluated by means of a determination of serum creatinine, which will be analyzed with the spectrophotometry method and from its result the glomerular filtration rate is calculated.	90 days
Secondary	Albumin/creatinine ratio	Before and after intervention by spectrophotometry	90 days
Secondary	Fasting plasma glucose	Before and after intervention spectrophotometry	90 days
Secondary	Glycated Hemoglobin concentration	It will be analyzed by liquid chromatography	90 days
Secondary	Systolic and diastolic arterial pressure	Before and after intervention using a digital baumanometer	90 days
Secondary	Alanine aminotransferase	Before and after intervention by spectrophotometry	90 days
Secondary	Aspartate aminotransferase	Before and after intervention by spectrophotometry	90 days