Dietary Polyphenols and Glycation in Renal Insufficiency (PoGlyDRI)

PoGlyDRI - Impact of Dietary Polyphenols on Protein Glycation in Type 2 Diabetes Mellitus Subjects With Chronic Renal Insufficiency

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of kidney failure, with high levels of glycohaemoglobin (HbA1c) presenting a sharper decline in renal function and an increase in the risk of mortality and end-stage renal disease (ESRD). Polyphenols may improve renal insufficiency in patients with diabetes with chlorogenic acids (CGA) one of the principle polyphenol groups in the diet - coffee/tea, stone fruits (especially plums/prunes) and some vegetables (artichoke, chicory). CGA (3-4 cups of coffee) has been associated with 25% lower risk of T2DM and a favourable reduction of HbA1c, blood pressure, and oxidative stress levels. This randomised controlled trial, therefore, aims to evaluate the effect of high CGA food on glycation and oxidative stress in T2DM subjects with early renal insufficiency (glomerular filtration rate of 35-60 mL/min) as well as progression of renal insufficiency and the risk of cardiovascular diseases.

The study will have two phases - phase I, an interventional study of 3 months followed by phase II, an observational study of 21 months.

In phase I, subjects will be randomized into 2 groups: CGA-enriched diet group, or control (habitual) diet group. The treatment group will be provided with a chlorogenic acid-rich food (coffee) with instructions to achieve an intake of 400 mg per day (equivalent to 3-4 coffee cups per day) for 12 weeks. The control group will receive a conventional coffee low in chlorogenic acid.

Participants will attend three sessions during phase I; baseline, 6 weeks, and 12 weeks. At baseline, general information, medical history, dietary habits and medication use will be recorded and a Food Frequency Questionnaire completed. Urine and blood samples will be collected and blood pressure, waist circumference, height and weight recorded. Participants' diet over the previous 3 days will be assessed by estimated food diary analysis.

In phase II, written dietary recommendations will be provided at three time points (months 6, 12 and 24) - treatment group to achieve a CGA-rich diet (total polyphenol intake of at least 1g per day, and at least 400mg per day of CGA) and standard dietary advice for the control group. Anthropometric/dietary data will be collected as well as blood and urine samples to assess markers of renal function, glycation and oxidative stress, and proteomic markers of cardiovascular disease, coronary artery disease and diabetes.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic
• Intervention / Treatment: Dietary supplement: Chlorogenic Acid (CGA) enriched coffee; Dietary supplement: Conventional coffee

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Glasgow, United Kingdom
    • NHS Greater Glasgow and Clyde
  • Glasgow, United Kingdom
    • University of Glasgow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• type 2 Diabetes Mellitus
• chronic renal insufficiency with persistent eGFR of 35-60mL/min for at least three months
• fluent in English

Exclusion Criteria:

• dialysis therapy (current or previous)
• malignancy
• transplant recipient
• hyperthyroidism
• hypothyroidism
• high dose glucocorticoids (≥250 mg)
• body mass index (BMI) ≥ 45 kg/m2
• special dietary requirements
• take creatine, antioxidants or vitamin supplements
• smoker
• pregnant
• consume >4 cups of tea/coffee per day
• consume >5 portion of fruits and vegetables per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment group; Chlorogenic Acid (CGA) 400mg/day (CGA-enriched coffee)	Dietary supplement: Chlorogenic Acid (CGA) enriched coffee; Chlorogenic Acid (CGA) enriched coffee Phase I: CGA-enriched coffee provided with a CGA content of 70-90 mg/100g. Daily CGA intake of 400mg. Phase II: recommendation for achieving a CGA-rich diet of at least 400mg/day (total polyphenol intake of at least 1g/day); Other Names: CGA-enriched diet
SHAM_COMPARATOR: Control group; Conventional coffee (habitual diet)	Dietary supplement: Conventional coffee; Phase I: conventional coffee provided (low in CGA) Phase II: standard dietary advice; Other Names: Habitual diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in glycohaemoglobin (HbA1c)	3 months
Change in estimated glomerular filtration rate (eGFR)	21 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in fasting glucose	3 months
Change in fructosamine	3 months
Change in advanced glycation end product (AGE)	3 months
Change in soluble receptor for AGE (sRAGE)	3 months
Change in F2-isoprostane	3 months
Change in malondialdehyde (MDA)	3 months
Change in Urinary Albumin Excretion	21 months
Change in creatinine	21 months
Change in blood pressure	21 months
Change in crystatin C	21 months
Change in fibrinogen	21 months
Change in cholesterol	21 months
Change in C-reactive protein	21 months
Change in Interleukin-6	21 months
Change in thiobarbituric acid reactive substances (TBARS)	21 months
Change in advanced oxidation protein products (AOPP)	21 months
Change in 8hydroxy 2'deoxyguanoside (8OhdG)	21 months

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde
• Collaborators: University of Glasgow

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): September 1, 2022
• Study Completion (ACTUAL): September 1, 2022

Study Registration Dates

• First Submitted: July 14, 2015
• First Submitted That Met QC Criteria: August 13, 2015
• First Posted (ESTIMATE): August 17, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Protein glycation; Dietary polyphenols
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: GN15DI242

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No