Clinical trial NCT02524938: Dietary Polyphenols and Glycation in Renal Insufficiency
Official title: PoGlyDRI - Impact of Dietary Polyphenols on Protein Glycation in Type 2 Diabetes Mellitus Subjects With Chronic Renal Insufficiency
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Renal Insufficiency, Chronic
Keywords: Dietary polyphenols
Protein glycation
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
First posted: 2015-08-17
Enrollment: 9
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in glycohaemoglobin (HbA1c)
timeFrame: 3 months
measure: Change in estimated glomerular filtration rate (eGFR)
timeFrame: 21 months
Secondary outcomes:
measure: Change in fasting glucose
timeFrame: 3 months
measure: Change in fructosamine
timeFrame: 3 months
measure: Change in advanced glycation end product (AGE)
timeFrame: 3 months
measure: Change in soluble receptor for AGE (sRAGE)
timeFrame: 3 months
measure: Change in F2-isoprostane
timeFrame: 3 months
measure: Change in malondialdehyde (MDA)
timeFrame: 3 months
measure: Change in Urinary Albumin Excretion
timeFrame: 21 months
measure: Change in creatinine
timeFrame: 21 months
measure: Change in blood pressure
timeFrame: 21 months
measure: Change in crystatin C
timeFrame: 21 months
measure: Change in fibrinogen
timeFrame: 21 months
measure: Change in cholesterol
timeFrame: 21 months
measure: Change in C-reactive protein
timeFrame: 21 months
measure: Change in Interleukin-6
timeFrame: 21 months
measure: Change in thiobarbituric acid reactive substances (TBARS)
timeFrame: 21 months
measure: Change in advanced oxidation protein products (AOPP)
timeFrame: 21 months
measure: Change in 8hydroxy 2'deoxyguanoside (8OhdG)
timeFrame: 21 months
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: Glasgow
country: United Kingdom
facility: University of Glasgow
Study officials:
affiliation: University of Glasgow
name: Emilie Combet, PhD
role: PRINCIPAL_INVESTIGATOR
References: