An interventional study of Apple polyphenols and Placebo in Prevention of Hyperglycaemia, sponsored by King's College London. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-06-17.
Sponsored by King's College London · Not applicable, Interventional, and Prevention
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.
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.
713 studies on the registry are indexed under Hyperglycemia; 108 are open to participants now.
This study's enrollment of 34 is below the median of 45 across 531 interventional studies indexed under Hyperglycemia.
Browse Hyperglycemia studies →King's College London is the lead sponsor of 519 studies on the registry; 126 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
1200 mg apple polyphenols delivered in a low sugar drink.
Dietary Supplement: Apple polyphenols
900 mg apple polyphenols delivered in a low sugar drink.
Dietary Supplement: Apple polyphenols
600 mg apple polyphenols delivered in a low sugar drink.
Dietary Supplement: Apple polyphenols
No polyphenols delivered in a low sugar drink.
Dietary Supplement: Placebo
Drinks will be delivered in random order at 4 separate study visits immediately before a high-carbohydrate meal. Seven days wash-out period will be required between study days.
Postprandial Glycaemia
Primary outcome: Area over baseline t+0-30 min for plasma glucose
Time frame: 30 min following the test drink
Postprandial Insulinaemia
Peak postprandial insulin concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Glucose-dependent Insulinotropic Polypeptide (GIP) Concentrations
Peak postprandial GIP concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Glucagon-like Peptide-1 (GLP-1) Concentrations
Peak postprandial GLP-1 concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial C-peptide Concentrations
Peak postprandial C-peptide concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Non-esterified Fatty Acid (NEFA) Concentrations
Peak postprandial NEFA concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Triglyceride (TAG) Concentrations
Peak postprandial TAG concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Paracetamol Concentrations
Peak postprandial paracetamol concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min (1.5 g paracetamol will be added to all test drinks in a sub-group of participants).
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Postprandial Polyphenol Metabolite Concentrations
Peak postprandial polyphenol metabolites concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Time frame: baseline and 10, 20, 30, 45, 60, 75, 90, 120, 150, 180, 240 min following the test drink
Vascular Endothelial Function by Flow-mediated Dilation (FMD)
Change in FMD after the consumption of test drink.
Time frame: baseline and 120, 240, 300 min following the test drink
Vascular Function (Arteriograph Measurement)
Change in augmentation index following the test drink.
Time frame: Baseline and 60, 90, 120, 180, 240 min following the test drink
Blood Pressure
Change in blood pressure following the test drink.
Time frame: Baseline and 60, 90, 120, 180, 240 min following the test drink
Urinary Polyphenol Metabolites
Change in urinary polyphenol metabolite concentration following the test drink.
Time frame: 0-4 h, 4-8 h, 8-24 h following the test drink
Urinary Glucose
Change in urinary glucose concentration following the test drink.
Time frame: 0-4 h, 4-8 h, 8-24 h following the test drink
7-day Food Diary
Habitual dietary intake analysis
Time frame: Baseline
Women's Health Questionnaire
Questionnaire to identify menstrual phase
Time frame: Baseline
Healthy participants were recruited from King's College London (KCL) and the general public in London and surrounding counties.
| Milestone | Doses of Apple Extract |
|---|---|
| Started | 34 |
| Completed | 30 |
| Not completed | 4 |
Primary outcome: Area over baseline t+0-30 min for plasma glucose
| mmol/L*min | 1.8 g Apple Extract | 1.2 g Apple Extract | 0.9 g Apple Extract | 0 g Apple Extract |
|---|---|---|---|---|
| Postprandial Glycaemia | 11.3 ± 1.2 | 15.2 ± 1.5 | 17.8 ± 1.6 | 27.1 ± 2.5 |
Peak postprandial insulin concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Peak postprandial GIP concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Peak postprandial GLP-1 concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Peak postprandial C-peptide concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Peak postprandial NEFA concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min
Results for this outcome have not been posted.
Peak postprandial TAG concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Peak postprandial paracetamol concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min (1.5 g paracetamol will be added to all test drinks in a sub-group of participants).
Results for this outcome have not been posted.
Peak postprandial polyphenol metabolites concentrations (Cmax) t +0-30 min and change from baseline data and areas over baseline t+0-30 min and t+0-240 min.
Results for this outcome have not been posted.
Change in FMD after the consumption of test drink.
Results for this outcome have not been posted.
Change in augmentation index following the test drink.
Results for this outcome have not been posted.
Change in blood pressure following the test drink.
Results for this outcome have not been posted.
Change in urinary polyphenol metabolite concentration following the test drink.
Results for this outcome have not been posted.
Change in urinary glucose concentration following the test drink.
Results for this outcome have not been posted.
Habitual dietary intake analysis
Results for this outcome have not been posted.
Questionnaire to identify menstrual phase
Results for this outcome have not been posted.
Collected over 5 hour study visit for each of the 4 interventions.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| 1.8 g Apple Extract | — | 0/34 (0%) | 0/34 (0%) |
| 1.2 g Apple Extract | — | 0/34 (0%) | 0/34 (0%) |
| 0.9 g Apple Extract | — | 0/34 (0%) | 0/34 (0%) |
| 0 g Apple Extract | — | 0/34 (0%) | 0/34 (0%) |
| Age, Customized(years) | All Study Participants |
|---|---|
| Males | 30 ± 12 |
| Premenopausal females | 27 ± 8 |
| Postmenopausal females | 56 ± 7 |
| Sex: Female, Male(Participants) | All Study Participants |
|---|---|
| Female | 19 |
| Male | 11 |
| Race and Ethnicity Not Collected(Participants) | All Study Participants |
|---|
| Region of Enrollment(participants) | All Study Participants |
|---|---|
| United Kingdom | 30 |
| Fasting glucose(mmol/L) | All Study Participants |
|---|---|
| Mean | 5.18 ± 0.39 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
The record gives a start of Jan 2017, a primary completion of Nov 2017 and a completion of Feb 2018. It does not say whether these dates are actual or estimated.
Results were first posted in Jun 2020, 2 years 7 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.