Clinical trial NCT02940249: Effects of an Apple Extract on Glycaemia: The GLU-Pomme Study
Official title: Dose-response Effect of an Apple Extract on Postprandial Glycaemia: a Randomised Controlled Trial. The GLU-POMME Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Prevention of Hyperglycaemia
Keywords: Polyphenol
Apple
Fruit
Hyperglycaemia
Metabolic
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: DIANA Food
First posted: 2016-10-20
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Postprandial hyperglycaemia can lead to adverse modifications to functional proteins within the body and eventually lead to the development of type 2 diabetes. Previous research by this group has shown that an apple polyphenol extract reduced hyperglycaemia following a high-carbohydrate meal. The aim of this study is to investigate the effects of lower doses of the apple extract on postprandial glycaemia, insulinaemia and plasma gastric inhibitory polypeptide concentrations following a mixed carbohydrate test meal.

Detailed description: Introduction:

Sharp peaks in blood glucose levels can lead to adverse modifications to functional proteins, oxidative stress and pancreatic beta cell dysfunction. It is therefore desirable to consume a diet that will allow more gradual rises in blood glucose levels after meals. Fruit polyphenols may help to limit the glucose excursion following a high carbohydrate meal. Previous research by this research group has demonstrated that 1200 mg of apple polyphenols (Appl'In™) inhibited the average incremental area under the curve (T+0 to T+30 min) of plasma glucose by 54% relative to placebo. Possible mechanisms include inhibition of intestinal enzymes and inhibition of intestinal glucose absorption by decreasing SGLT1/GLUT2 transport activity. The literature also suggests that foods rich in polyphenols exert beneficial effects on risk factors of cardiovascular disease such as hypertension, lipid metabolism and vascular function.

Study design:

A randomised, controlled, double-blind, cross-over study will be conducted. Four matched test drinks will be consumed in random order on separate study visits immediately before a mixed-carbohydrate test meal, containing either: 1) 1.2 g, 2) 0.9 g 3). 0.6 g of apple polyphenols, or 4). placebo. Postprandial changes in plasma glucose, insulin, NEFA, GIP, GLP-1 concentrations as well as changes in vascular function will be measured. Twenty-four hour urine samples will be collected for analysis of urinary polyphenol metabolites and glucose. In a sub sample of participants, a paracetamol absorption test will be incorporated via addition of 1.5 g paracetamol into the test drink.

Eligibility criteria: Inclusion Criteria:

* Age: 18-70 y
* Male and female
* Healthy (free of diagnosed diseases listed in the exclusion criteria)
* Body Mass Index 18-35 kg/m2
* Able to understand the information sheet and willing to comply with study protocol
* Able to give informed written consent

Exclusion Criteria:

* Those diagnosed with Phenylketonuria (PKU)
* Those with known or suspected food and/or paracetamol intolerances, allergies or hypersensitivity
* Women who are known to be pregnant or who are intending to become pregnant over the course of the study
* Women who are breast feeding
* Participation in another clinical trial
* Those who have donated blood within 3 months of the screening visit and participants for whom participation in this study would result in having donated more than 1500 millilitres of blood in the previous 12 months.
* Full Blood Counts and Liver Function test results outside of the normal range.
* Current smokers, or reported giving up smoking within the last 6 months
* History of substance abuse or alcoholism
* Reported history of Cardiovascular disease, diabetes (or fasting glucose ≥ 7.1 mmol/L), cancer, kidney, liver or bowel disease, gastrointestinal disorder or use of drug likely to alter gastrointestinal function
* Unwilling to restrict consumption of specified high polyphenol foods for 48 h before the study
* Weight change \>3kg in preceding 2 months and body mass index \<18 or \>35 kg/m2
* Blood pressure ≥160/100 mmHg
* Total cholesterol ≥ 7.5 mmol/L; fasting triacylglycerol concentrations ≥ 5.0 mmol/L
* Medications that may interfere with the study: alpha-glucosidase inhibitors (acarbose: Glucobay), insulin sensitizing drugs (metformin: Glucophage, Glucophage SR, Eucreas, Janumet; thiazolidinediones: Actos, Competact), sulfonylureas (Daonil, Diamicron, Diamicron MR, Glibenese, Minodiab, Amaryl Tolbutamide), and lipid lowering drugs (statins, nicotinic acid, colestyramine anhydrous, ezetimibe, fibrates); and medications that may react unpredictably with paracetamol: ketoconazole, metoclopramide, carbamazepine, phenobarbital, phenytoin, primidone, warfarin and other products containing paracetamol. Other medications should be reviewed by medical representative from KCL on a case by case basis.
* Nutritional supplements that may interfere with the study: higher dose vitamins/minerals (\>200% Recommend Nutrient Intake), B vitamins, Vitamin C, calcium, copper, chromium, iodine, iron, magnesium, manganese, phosphorus, potassium and zinc. Subjects already taking vitamin or minerals at a dose around 100% or less up to 200% of the RNI, or evening primrose/algal/fish oil supplements will be asked to maintain habitual intake patterns, ensuring that they take them every day and not sporadically. They will be advised not to stop taking supplements or start taking new supplements during the course of the study.

Primary outcomes:
measure: Postprandial Glycaemia
timeFrame: 30 min following the test drink
Secondary outcomes:
measure: Postprandial Insulinaemia
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Glucose-dependent Insulinotropic Polypeptide (GIP) Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Glucagon-like Peptide-1 (GLP-1) Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial C-peptide Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Non-esterified Fatty Acid (NEFA) Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Triglyceride (TAG) Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Paracetamol Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Postprandial Polyphenol Metabolite Concentrations
timeFrame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
measure: Vascular Endothelial Function by Flow-mediated Dilation (FMD)
timeFrame: baseline and 120, 240, 300 min following the test drink
measure: Vascular Function (Arteriograph Measurement)
timeFrame: Baseline and 60, 90, 120, 180, 240 min following the test drink
measure: Blood Pressure
timeFrame: Baseline and 60, 90, 120, 180, 240 min following the test drink
measure: Urinary Polyphenol Metabolites
timeFrame: 0-4 h, 4-8 h, 8-24 h following the test drink
measure: Urinary Glucose
timeFrame: 0-4 h, 4-8 h, 8-24 h following the test drink
Other outcomes:
measure: 7-day Food Diary
timeFrame: Baseline
measure: Women's Health Questionnaire
timeFrame: Baseline
Locations:
city: Waterloo Campus
country: United Kingdom
facility: Metabolic Research Unit at King's College London
state: London
Study officials:
References: