Condition category
Nutritional, Metabolic, Endocrine
Date applied
19/08/2013
Date assigned
06/11/2013
Last edited
22/09/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Dietary carbohydrates consist mainly of glucose molecules arranged together in different structures. Due to the wide variety of carbohydrates in the diet, humans have evolved a set of enzymes to digest carbohydrates efficiently to produce glucose, the body’s energy source. The level of glucose in your bloodstream after eating a digestible carbohydrate such as starch is related to the food’s glycaemic index (GI). It is not currently understood how genetic variation affects digestion, or blood glucose levels, but it may be clinically relevant to identify people at risk of developing type 2 diabetes. This study will investigate whether variations in your DNA (your genetic make-up) affect how carbohydrates are digested and we will do this by measuring levels of glucose and insulin in your blood after eating carbohydrates. A study that investigates the body’s response to food is called a ‘postprandial’ study, which literally means ‘after eating’.

Who can participate?
We require healthy, non-smoking, men and women aged between 18-40 years old. We are looking for British participants who were born in the UK and who have four grandparents that were also born in the UK.

What does the study involve?
This research is being conducted in two stages. Stage 1 involves saliva sample donation for DNA extraction and genetic analysis. DNA will be used for screening for participation in Stage 2, for investigating the frequency of genetic variation in carbohydrate enzymes in the UK population. Therefore, DNA collected during Stage 1 will be used in this research project even if participants do not participate in the postprandial study. Stage 2 is the postprandial study, where participants will be selected based on inclusion/exclusion criteria and the outcome of genetic screening from Stage 1. Stage 2 involves a health check visit and two study days. If participants do not wish to participate in the postprandial study (Stage 2), but would like to donate your DNA to this research project (Stage 1), they may be able to do this. However, it is not possible to participate in the postprandial study (Stage 2) if a saliva sample is not provided in Stage 1.

Stage 1 – Genetic screening and DNA donation
During the first visit, participants will be asked to sign an informed consent form and complete a registration questionnaire. They will be assigned a unique ID number, which is recorded along with contact details and held securely, to ensure they cannot be identified. We will then collect saliva samples, from which DNA will be extracted and genetic testing will be carried out. Genetic screening is used only as a research logistic, and has no potential clinical significance or implications for health. We are looking for a range of genetic variations, known as genotypes. The genotypes that we are interested in for the purpose of this study are present in 60% of the population. Therefore, we will only be contacting about 60 participants from Stage 1 to take part in Stage 2, health screening. After the health screening we will then enrol about 48 volunteers into the postprandial study. Volunteers will be asked to complete a 3-day diet diary to assess habitual dietary intakes before taking part in Stage 2.

Stage 2 – Health screening and postprandial study
We will contact volunteers with the genotypes of interest to attend a health screening appointment (lasting about 45 minutes) in the Metabolic Unit, 4th Floor, Corridor A, Franklin-Wilkins Building, KCL. Volunteers will need to attend this visit after an overnight fast (no food or drink except water after 10 pm the night before). Volunteers will be asked to complete a 3-day diet diary to assess habitual dietary intakes. At the health screening appointment we will take a small blood sample (25 ml, or 5 teaspoons) which we will use to determine whether liver function, blood count, blood glucose, blood insulin and blood fats such as cholesterol are within normal ranges. We will also take the following measures: height, weight, waist and hip circumference, body fat percentage, blood pressure and heart rate. Once we have received the results, we will contact volunteers and provide them with a copy of the results. If any health concerns arise from these tests we will also send a copy of the results to their GP, using the details provided on the registration form, so that they can be followed up if wished.

During the postprandial study we will take blood samples over a period of 4 hours by inserting a single fixed needle (cannula) into a vein on the forearm, from which all blood samples will be taken. We shall take three small blood samples (9 ml, two teaspoons) for baseline measures. We will then ask participants to consume the test meal, which contains 75 g of carbohydrate; they will have 5 minutes to consume this. We shall then take further blood samples at 15-minute intervals for the first hour and then at 30-minute intervals between 1 and 4 hours. 13 blood samples will be taken on the study day, a total of 216 ml blood. A grand total of 457 ml of blood will be collected over the whole study period (25 ml at screening and 216 ml on each study day); this is less than the amount taken in a standard blood donation session. At the end of the 4 hours, the cannula will be removed and you will be provided with a choice of snacks to consume before you leave. Each participant must attend two study days, they will receive a different test meal on each visit.

What are the possible benefits and risks of participating?
The benefits are a comprehensive health check, and participants will be helping to improve our understanding of the causes of type 2 diabetes. Participants that complete the entire study will receive compensation of £80 plus up to £10 reimbursement for their travel costs per visit. There is very little risk to the participants; all blood samples will be taken by highly trained professionals and the methods used have been used and reproduced safely many times.

Where is the study run from?
The study is being run from the University College London, UK. Participants will also be required to attend the Metabolic Unit in the Franklin-Wilkins building of King’s College London, UK.

When is the study starting and how long is it expected to run for?
Recruitment is expected to start in March 2014. The full length of participation for a volunteer is expected to be 6-9 weeks, depending on availability. The study is expected to run until December 2014.

Who is funding the study?
This study is funded by Biotechnology & Biological Sciences Research Council (BBSRC), UK.

Who is the main contact?
Miss Katherine Brown
katherine.brown.11@ucl.ac.uk or genCHOstudy@kcl.ac.uk
+44 (0)20 7679 4397

Trial website

Contact information

Type

Scientific

Primary contact

Prof Mark G. Thomas

ORCID ID

Contact details

Department of Genetics
Evolution & Environment
University College London
Darwin Building
Gower Street
London
WC1E 6BT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

An acute investigation into the relationship between genetic variation, digestion and blood glucose response upon consumption of carbohydrates

Acronym

GenCHO

Study hypothesis

Current hypothesis as of 10/03/2014:
The purpose of this research is to investigate whether genetic variation in the genes of carbohydrate digestive enzymes (CDEs) affects postprandial glycaemic and or insulinaemic response after consumption of carbohydrates.

The principal objective is to collect blood samples for 4 hours after consumption of the test CHO; these blood samples will be analysed for blood glucose and insulin levels. This study is designed to have two groups per gene, and will compare the glycaemic and insulinaemic responses between the two groups testing the same gene. This will enable us to identify differences in glycemic response that are due to enzyme activity caused by underlying genetic variation.

This study will help to unravel the involvement of carbohydrate digestion in the development and management of type 2 diabetes. We hope to identify genetic variants that affect the activity of digestive enzymes that cause elevated glycemic response after ingestion of carbohydrates. This study will also be able to investigate whether genetic variation in carbohydrate digestion enzymes explains the variability of glycemic response within the normal observed range.

In summary the question is: does genetic variation in genes coding for carbohydrate digestive enzymes affect digestion and impact the rate, peak or total glucose and/or insulin response when an individual consumes carbohydrate?

Secondary Objectives
The secondary objective is to use blood samples collected from this study to investigate whether different CHOs produce different responses in the gut hormones responsible for satiety. Measuring and comparing levels of c-peptide, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY) and cholecystokinin (CCK), between groups ingesting different CHOs and also between sub-groups, will achieve this. This will contribute towards our understanding of how the food we eat makes us feel full and satisfied; much work has been done on this in regards to protein and fat ingestion but there remains a lot which is unknown in relation to consumption of CHO.

All DNA samples collected in this study will be used to estimate the frequency of genetic variations in carbohydrate digestive enzymes within the UK population. The frequency of these variations in the UK will then be compared to frequencies in global populations and used to interpret the cause for any population-specific distribution. This will contribute towards understanding human evolution and adaptation to dietary changes.

Previous hypothesis:
The purpose of this research is to investigate whether genetic variants in the genes of carbohydrate digestive enzymes (CDEs) affects postprandial glycemic and or insulinemic response after consumption of carbohydrates.

The principal objective is to collect blood samples for 4-hours after consumption of the test CHO solution. These blood samples will be analysed for blood glucose and insulin levels. This study is designed to have a case and a control group per CDE, as different CHOs elicit different glycemic response due to their composition. The glycemic and insulinemic responses will be compared between case and control groups for the same CDE, this will enable us to identify differences in glycemic response that are due to enzyme activity and not due to CHO composition.

This study will help to unravel the involvement of carbohydrate digestion in the development and management of type-2 diabetes. We hope to identify genetic variants that affect the activity of digestive enzymes that cause elevated glycemic response after ingestion of carbohydrates. This study will also be able to investigate whether genetic variation in carbohydrate digestion enzymes explains the variability of glycemic response within the normal observed range.

In summary the question is: does genetic variation in genes coding for carbohydrate digestive enzymes affect digestion and impact the rate, peak or total glucose and/or insulin response when an individual consumes carbohydrate?

Secondary Objectives
The secondary objective is to use additional blood samples collected from this study to investigate whether different CHOs produce different responses in the gut hormones responsible for satiety. Measuring and comparing levels of c-peptide, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY) and cholecystokinin (CCK), between groups ingesting different CHOs and also between case and control groups, will achieve this. This will contribute towards our understanding of how the food we eat makes us feel full and satisfied, much work has been done on this in regards to protein and fat ingestion but there remains a lot which is unknown in relation to consumption of CHO.

All DNA samples collected in this study will be used to estimate the frequency of genetic variations in CDEs within a healthy sample of the UK population. The frequency of these variations in the UK will then be compared to frequencies in global populations and used to interpret the cause for any population specific distribution. This will contribute towards understanding human evolution and adaptation to dietary changes.

On 10/03/2014 the following changes were made to the trial record:
1. The scientific title was changed from 'An acute case-control investigation into the relationship between genetic variation, digestion and blood glucose response upon consumption of carbohydrates' to 'An acute investigation into the relationship between genetic variation, digestion and blood glucose response upon consumption of carbohydrates'
2. The study design was changed from 'Case-control single-center double-blind single-dose intervention study' to 'Single-center double-blind single-dose intervention study'
3. The anticipated start date was changed from 06/01/2014 to 10/03/2014
4. The target number of participants was changed from 80 to 48

Ethics approval

NHS Research Ethics Committee London - Harrow, ref: LO/14/0063

Study design

Single-center double-blind single-dose intervention study

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

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

Condition

Nutritional health relating to carbohydrate digestion and metabolism, scope includes but the study is not designed to test association to type 2 diabetes

Intervention

Current interventions as of 22/09/2014:
As part of the screening procedures, participants will make a saliva sample by spitting into a collection pot. This is pain free and will be demonstrated to them. A small fasting blood sample will also be taken as part of the health screening processes; this will be done following standard venepuncture procedures and performed by highly trained professionals.

Participants will attend two study days where they will be asked to consume the test meals. The test meals each contain 75 g of carbohydrate. On one visit, a test meal will be given in the form of a drink, and on the other visit this will be given as cooked white rice, which is six tablespoons of rice (uncooked). Treatment allocation is randomized, so each participant will receive both test meals, but in a random order.

During each of the study days a fixed needle (cannula) will be inserted into the forearm of the participants following standard procedures and performed by a study clinician or nurse. This may cause temporary discomfort but has no long-lasting effects. The study day procedures follow that of a 4-hour oral glucose tolerance test (OGGT). Baseline samples will be collected using this cannula, as will all other blood samples collected during the study period.

Interventions from 10/03/2014 to 22/09/2014:
As part of the screening procedures, participants will make a saliva sample by spitting into a collection pot. This is pain free and will be demonstrated to them. A small fasting blood sample will also be taken as part of the health screening processes; this will be done following standard venepuncture procedures and performed by highly trained professionals.

During the study day a fixed needle (cannula) will be inserted into the forearm of the participants following standard procedures and performed by a study clinician or nurse. This may cause temporary discomfort but has no long-lasting effects. The study day procedures follow that of a 4-hour oral glucose tolerance test (OGGT). Baseline samples will be collected using this cannula, as will all other blood samples collected during the study period.

Participants will attend a single study day where they will be asked to consume a single test suspension. Test suspensions will contain 75 g of either trehalose, maltose, sucrose or corn starch, suspended in 500 ml of drinking water. The test suspension that a participant will receive shall be based on the group that they are in, which is allocated on the outcome of the genetic screening at the start of this study. There are four study arms, represented by the four different test suspensions; this study is not designed as a cross-over so each participant will only consume one test suspension and attend only one study day.

Interventions at time of registration:
As part of the screening procedures, participants will make a mouth swab by lightly wiping a cotton swab on the inside of their cheek for approximately 30 seconds. This is pain free and will be demonstrated to them. A small fasting blood sample will also be taken as part of the health screening processes; this will be done following standard venepuncture procedures and performed by highly trained professionals.

During the study day a fixed needle (cannula) will be inserted into the forearm of the participants following standard procedures and performed by a study clinician or nurse. This may cause temporary discomfort but has no long-lasting effects. The study day procedures follow that of a 4-hour oral glucose tolerance test (OGGT). Baseline samples will be collected using this cannula, as will all other blood samples collected during the study period.

Participants will attend a single study day where they will be asked to consume a single test suspension. Test suspensions will contain 75 g of either trehalose, maltose, sucrose or corn starch, suspended in 500 ml of drinking water. The test suspension that a participant will receive shall be based on the group that they are in, which is allocated on the outcome of the genetic screening at the start of this study. There are four study arms, represented by the four different test suspensions; this study is not designed as a cross-over so each participant will only consume one test suspension and attend only one study day.

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

Current primary outcome measures as of 10/03/2014:
The primary outcome measures will be the postprandial changes in indices of glucose metabolism and insulin secretion. Blood samples will be collected for the analysis of plasma glucose and plasma insulin.

Previous primary outcome measures:
Primary outcome measures are plasma glucose and plasma insulin concentrations, which are to be measured at t = baseline (blood samples taken before the participant consumes the test carbohydrate.-15, -5), 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins. Plasma glucose is used to determine postprandial glycaemic responses and plasma insulin is used to determine postprandial insulinaemic responses.

Secondary outcome measures

Current secondary outcome measures as of 10/03/2014:
Secondary outcome measures will be to use blood samples collected in the postprandial study to analyse the effect of gut hormone response to the ingestion and digestion of different CHOs. This will be done by analysing concentrations of gut hormones including incretin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like polypeptide-1 (GLP-1) peptide YY (PYY) and cholecystokinin (CCK). Blood fractions for C-peptide analysis will also be collected, as a marker of the rate of insulin synthesis, to be used in addition to insulin concentrations to understand the postprandial insulinaemic response. Finally, the DNA samples collected in this study will be used to further investigate genetic variation in the genes of CDEs and to estimate the frequency of the polymorphic genetic loci in CDEs within the healthy UK population. This data will then be used in population-based genetic analysis to draw conclusions about human evolution and adaptation to dietary changes.

Previous secondary outcome measures:
Further genetic analysis of the DNA samples collected in this study will take place after the conclusion of the trial so that participants do not lose interest. The informed consent form signed prior to swab collection ensures that the volunteers know that their DNA will be analysed using population genetic techniques. Data generated from genetic analysis of DNA samples collected as part of this trial will be analysed to make estimates of the frequency of variant alleles in CDEs within the healthy UK population. Doing this in conjunction with the latter stages of this trail may identify new genetic variants that affect the digestive health of the UK population. These data will also be incorporated into genotype data collected bioinformatically to inform on the global distribution of the studied genetic variants.

Secondary outcome measures of blood-borne molecules include:
1. C-peptide concentrations measured at t = -15, -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins, which is used to assess insulin secretion and provide an additional measurement of insulin metabolism.
2. Concentration of various gut hormones will also be measured as differences in the rates of absorption and digestion of the test carbohydrates may have subsequent effects on rates of gastric emptying and may affect the rates of glycaemic responses via gut hormone mediated effects which have subsequent implications for metabolism and satiety. Concentrations are measured at t = -15, -5, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 mins. The specific hormones are:
2.1. Glucose inhibitory peptide (GIP), which is released in response to a mixed meal and plays an important role in determining postprandial insulin concentrations, and acts as a good indicator of glucose absorption.
2.2. Peptide YY (PYY), which is associated with the postprandial handling of lipids, whereby ingested fat stimulates the release of PYY by an early, probably hormonal mechanism, and later by the entry of fat into the distal small intestine.
2.3. Glucagon-like peptide 1 (GLP-1), the secretion of which is influenced by the presence of carbohydrate, protein and lipid in the small intestine, and is involved in insulin regulation, gastric emptying and satiety.

Overall trial start date

10/03/2014

Overall trial end date

31/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 10/03/2014:
1. Healthy, non-smoking, men and women aged between 18-40 years old
2. British participants who were born in the UK and who have four grandparents that were also born in the UK

Previous inclusion criteria:
Healthy, non-smoking, men and women, aged 18-40 years, of British ethnicity

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

48

Participant exclusion criteria

Exclusion criteria identified during visit 1 using questionnaire:
1. The subject is an employee of Unilever
2. Medical history of myocardial infarction, angina, thrombosis, stroke, cancer or diabetes
3. Medical history of eating disorders such as anorexia nervosa, bulimia, binge eating disorder
4. Medical history of digestive dysfunction, or intestinal disease such as IBS and Crohn’s disease
5. Medical history of pancreatitis (Acute, Chronic or Hereditary) and exocrine pancreatic insufficiency
6. Alcohol intake exceeding a moderate intake (>28 units per week)
7. Needle phobic, fear of blood and blood clotting disorders such as haemophilia
8. Pregnant, breast-feeding and post-menopausal women

Exclusion criteria identified after visit 2, using genetic and health screening methods:
1. Fasting plasma glucose > 6.0 mmol /L
2. Fasting plasma insulin > 60 pmol/L
3. Fasting plasma cholesterol > 7.8 mmol /L
4. Body fat percentage < 8% or >25% for men and < 20% or >35% for women
5. Body mass index (BMI) <18.5 or >25.5
6. Blood pressure < 90/60 or >120/80
7. Abnormal liver function

The following will be recorded but are not considered grounds for exclusion, as there is no evidence that this will cause adverse response or distress to the subjects, but it may be of interest.
1. Diagnosed lactose intolerance
2. Confirmed gluten sensitivity, including coeliac disease

Recruitment start date

10/03/2014

Recruitment end date

31/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Department of Genetics, Evolution & Environment
London
WC1E 6BT
United Kingdom

Sponsor information

Organisation

University College London (UCL) (UK)

Sponsor details

Dr Clara Kalu
Joint Research Office (part of the Research Support Centre)
UCL
Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Research council

Funder name

Biotechnology & Biological Sciences Research Council (BBSRC) (UK) - CASE industrial studentship

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