Dietary Polyphenols and Glycation in Renal Insufficiency

Study Overview
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Brief Summary
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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.

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

Conditions
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Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic

Intervention / Treatment
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* Dietary Supplement: Chlorogenic Acid (CGA) enriched coffee
* Dietary Supplement: Conventional coffee


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group<br>Chlorogenic Acid (CGA) 400mg/day (CGA-enriched coffee) | Dietary Supplement: Chlorogenic Acid (CGA) enriched coffee<br>* 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)<br>* Other names: CGA-enriched diet;|
| Sham Comparator: Control group<br>Conventional coffee (habitual diet) | Dietary Supplement: Conventional coffee<br>* Phase I: conventional coffee provided (low in CGA) Phase II: standard dietary advice<br>* Other names: Habitual diet;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dietary polyphenols, Protein glycation