Condition category
Nutritional, Metabolic, Endocrine
Date applied
23/02/2014
Date assigned
16/04/2014
Last edited
06/07/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Polycystic Ovary Syndrome (PCOS) is characterised by insulin resistance (body tissues have a reduced response to the effect of insulin). PCOS is made worse by obesity and by increased insulin levels. A reduction in insulin sensitivity (ability of body tissues to respond to action of insulin) and a decrease in the production of nitric oxide (released from the lining of the blood vessels, which causes them to relax allowing blood to flow normally) expose women with this condition to an increased risk for diabetes and heart disease. Substances present in green tea and coffee are called polyphenols. They appear to have beneficial effects on the regulation of blood glucose and on risk factors for heart disease (e.g. elevated blood pressure). However there is not enough evidence from previous research. This study evaluated the potential positive effect of green tea and coffee polyphenols on insulin sensitivity, nitric oxide production and risk factors for heart disease in overweight and obese women with PCOS and insulin resistance.

Who participated?
Pre-menopausal, overweight or obese women with PCOS and insulin resistance who are 16-45 years of age.

What did the study involve?
All participants took placebo (dummy) tablets for 8 weeks and green tea and coffee polyphenol tablets for the following 8 weeks. Height, weight, waist circumference and body fat percentage, glucose control, heart function measurements and other related parameters were tested before and after intake of placebo and polyphenol tablets. In addition diet and physical activity level were assessed and safety and compliance checks were conducted at these times. Consumption of foods containing polyphenols (e.g. fruits, vegetables, cocoa products, etc.) was only restricted during the 3 days before each main study visit. The effect of the polyphenol tablets will be compared with that of the dummy treatment.

What were the possible benefits and risks of participating?
Participants benefited from been screened for diabetes, high cholesterol, triglycerides and high blood pressure. They were given the option to know their weight, body mass index (BMI) and body fat percentage throughout the study. Participants also learned about the overall results of the study (mainly in relation to glucose control and heart function). Knowledge gained from this study could help our understanding of the potential use of polyphenols in protecting against the development of diabetes and heart disease. The main risks associated with participation in this study were from blood taking which may have caused discomfort and minor bruising in some instances and side effects associated with the intake of the polyphenol tablets (e.g. mild stomach ache). No side effects were associated with taking the placebo treatment. The body composition measurement involved negligible exposure to ionizing radiation (equivalent to about 9 hours natural background radiation in the UK). The tests for insulin sensitivity and nitric oxide production involved the use of stable isotopes (naturally occurring molecules) which do not have any risk for human health.

Where was the study run from?
Medical Research Council (MRC) - Human Nutrition Research (HNR), Cambridge, UK.

When did the study start and finish?
Recruitment began in April 2012 and ended in July 2013. Participants were evaluated from June 2012 to November 2013.

Who is funding the study?
Medical Research Council (MRC) - Human Nutrition Research (HNR) (UK),, Cambridge, UK.

Who is the main contact?
Mrs Virginia Tomatis
virginia.tomatis@mrc-hnr.cam.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Virginia Tomatis

ORCID ID

Contact details

MRC Human Nutrition Research
Elsie Widdowson Laboratory
120 Fulbourn Road
Cambridge
CB1 9NL
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

6420

Study information

Scientific title

The effects of green tea and coffee polyphenols on insulin sensitivity and secretion and cardiovascular function in overweight and obese women with Polycystic Ovary Syndrome (PCOS) and insulin resistance

Acronym

POCMOS

Study hypothesis

Primary hypotheses:
1. Combined supplementation with green tea and coffee polyphenols will result in an increase in insulin sensitivity and improvement in insulin secretion in overweight and obese women with Polycystic Ovary Syndrome (PCOS) and insulin resistance.
2. Combined supplementation with green tea and coffee polyphenols will result in an increase in nitric oxide production.

Secondary hypotheses:
1.. Combined supplementation with green tea and coffee polyphenols will result in an improvement in vascular/endothelial function.
2. Insulin sensitivity and nitric oxide will be positively associated and they will be positively correlated with improved vascular/endothelial function.
3. Combined supplementation with green tea and coffee polyphenols will produce a reduction in oxidative stress and inflammatory biomarkers.
4. Combined supplementation with green tea and coffee polyphenols will result in a greater increase in insulin sensitivity and nitric oxide production (synergistic effect) compared with the results from previous studies investigating the effects of each substance alone in similar populations.

Ethics approval

Cambridge South Research Ethics Committee, Cambridge, UK, 02/03/2012, Ref: 11/EE/0465

Study design

Single-blind placebo-controlled unilateral cross-over study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet.

Condition

Polycystic Ovary Syndrome (PCOS), overweight/obesity and insulin resistance

Intervention

The study consisted of two intervention treatments:
1) Placebo treatment - placebo tablets
2) Active treatment (polyphenol supplements) - Green Tea extract (GTE) tablets (containing green tea catechins, GTC) and Verdesse® tablets (containing chlorogenic acids, CGA)

Green Tea extract (GTE) tablets were purchased from Healthspan (St Peter Port, UK). The total amount of GTC and CGA consumed by participants per day during the intervention period was approximately1938 mg and 600 mg respectively (approximately equivalent amount of GTC and CGA to that of drinking 8 to 13 cups of green tea and 2 to 9 cups of coffee per day). Participants took placebo tablets for eight weeks, followed by eight weeks of GTC and CGA tablets. GTC tablets (and their corresponding placebo tablets) were taken 30-60 minutes before breakfast, lunch and dinner. CGA tablets (and their corresponding placebo tablets) were taken immediately after breakfast, lunch and dinner).

Intervention type

Supplement

Phase

Drug names

Primary outcome measures

Insulin sensitivity and secretion were measured at baseline (week 0), post-placebo (week 8) and post-intervention (week 16) time points via the Oral Dose Intravenous Labelled Glucose Experiment (ODILE) protocol. The ODILE protocol is similar to the Oral Glucose Tolerance Test (OGTT), but it is modified by the addition of an intravenous dose of [1]-13C-glucose (labelled glucose) administered 45 minutes after the oral glucose dose was consumed (40 blood samples are taken over a 4-hour and 45 minute period). Gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) is used for isotopic composition and the results are interpreted using a stable-label two compartment minimal model (2CMM). This mathematical modelling allows for the determination of glucose effectiveness and insulin sensitivity parameters. Insulin and C-peptide data obtained from the same protocol were also modelled to obtain information about insulin secretion.

Secondary outcome measures

1. Nitric oxide production was also measured at baseline (week 0), post-placebo (week 8) and post-intervention (week 16) using the Oral Nitrate Test (ONT) protocol, which is based on the physiological characteristics of the entero-salivary circulation of plasma nitrate and involves the consumption of a very low nitrate meal, followed by the collection of six saliva samples over a 2-day period. Isotopic composition is measured using GC/MS. The protocol measures the disappearance of an oral dose of Na15NO3 (labelled sodium nitrate) in saliva samples. The isotopic decay is defined by an exponential function for a single compartment. Data are expressed using a semi-logarithmic plot and the slope and intercept of the regression line are utilised to calculate the NO production rate.
2. Vascular/endothelial function measurements were measured at the same time points as stated above; except for blood pressure which was also measured at 2 intermediate study visits (weeks 4 and 12). The measurements consisted of carotid intima media thickness (cIMT), pulse wave velocity (PWV) and blood pressure.

Overall trial start date

17/04/2012

Overall trial end date

27/11/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Otherwise healthy
2. Pre-menopausal, overweight or obese women (BMI ≥ 25 kg/m2)
3. Aged16-45 years
4. With PCOS and insulin resistance (fasting insulin ≥ 50 pmol/L)

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

12

Participant exclusion criteria

1. Smoking
2. History of substance abuse or alcohol consumption >14 units per week
3. Allergy or intolerance to the study supplements and/or foods
4. Professional athletes or those with self-reported high physical activity
5. Chronic, acute or active metabolic (including type 1 and type 2 diabetes mellitus) and inflammatory conditions, haematological disorders, or any other systemic illness of renal, hepatic or gastrointestinal origin
6. Active cancer or diagnosis of malignancy within the last five years
7. Major surgical operations interfering with the study outcomes within three months of screening
8. Medical treatment with the following agents: weight reduction medicines, insulin sensitizers, hormonal therapy, antihypertensive medicines, anti-dyslipidaemic agents, nitrate-derived agents, psychiatric drugs (only excluded if dose had been started/changed in the previous six months) or any other medication known to affect glucose/insulin metabolism, vascular/endothelial function, gastrointestinal system or central nervous system
9. Weight change > 10% over the last six months
10. Endocrine disorders such as adrenal hyperplasia, hyperprolactinaemia, Cushing’s syndrome, androgenic tumours, late onset of 21-hydroxylase deficiency, abnormal thyroid function or any other ovarian, adrenal or pituitary disorder not associated with PCOS
11. Pregnant, lactating, contemplating pregnancy or undergoing treatment to achieve pregnancy
12. Regular consumption of micronutrient and/or herbal and/or polyphenol supplements known to have an impact on insulin sensitivity/secretion and/or vascular/endothelial function

Recruitment start date

17/04/2012

Recruitment end date

01/07/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

MRC Human Nutrition Research
Cambridge
CB1 9NL
United Kingdom

Sponsor information

Organisation

Medical Research Council - Human Nutrition Research (UK)

Sponsor details

c/o Ms Polly Page
Elsie Widdowson Laboratory
120 Fulbourn Road
Cambridge
CB1 9NL
United Kingdom

Sponsor type

Research council

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) - Human Nutrition Research (HNR) (UK), programme number 5PT60

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes