|First Submitted Date ICMJE||April 5, 2013|
|First Posted Date ICMJE||April 26, 2013|
|Last Update Posted Date||November 21, 2016|
|Start Date ICMJE||March 2011|
|Primary Completion Date||August 2013 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Glycaemic control [ Time Frame: 18 weeks ]
Change in glycaemic control over 18 weeks both fasting and post-prandial. Measures of glycaemic control (glucose, insulin and the calculated values: HOMA-IR, Matsuda and Insulinogenic Index) will be measured at baseline, 9 and 18 weeks.
The delta change at baseline and 9 weeks, baseline and 18 weeks and 9 and 18 weeks will be compared between intervention groups.
The delta change between baseline and 18 weeks will be calculated.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01841073 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Food intake [ Time Frame: 18 weeks ]
Change in food intake following intervention over 18 weeks
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE
||Change in body weight [ Time Frame: 18 weeks ]
Change in body weight over 18 week intervention
|Original Other Outcome Measures ICMJE||Same as current|
|Brief Title ICMJE||Effect of Fermentable Carbohydrate on Glucose Homeostasis|
|Official Title ICMJE||Effect of Fermentable Carbohydrate on Glucose Homeostasis and Weight Management in Subjects With Prediabetes|
|Brief Summary||The rise in the prevalence of type 2 diabetes is related to recent lifestyle changes leading to a rise in obesity. Obesity is a risk factor for Impaired Glucose Tolerance (IGT) and diabetes. A type of fibre - fermentable carbohydrate - may help prevent diabetes in individuals with IGT by reducing appetite and food intake, and improving insulin sensitivity. Although fermentable carbohydrate is not absorbed in the small intestine it is full fermented by the colonic bacteria. The fermentation of this carbohydrate produces short chain fatty acids which act on specific G protein coupled receptors (GPR41/43) in the intestine to release GLP-1 and PYY. GLP-1 and PYY are hormones which act on appetite centres in the brain to decrease appetite. GLP-1 incretin effects and possible effect of the beta cell will increase insulin sensitivity. Short chain fatty acids also suppress the release of free fatty acids from adipocytes. Lower levels of free fatty acids in insulin resistant subject's leads to improved insulin sensitivity. This body of work will examine the effect of fermentable carbohydrate on appetite, weight loss, blood glucose control which will give an indication of the possibility of fermentable carbohydrate to prevent type 2 diabetes in this at-risk group.|
TITLE The Effect of Fermentable Carbohydrate on Weight Management and Glycaemic Control in People at High Risk of Developing DMT2
AIMS To assess the effect of fermentable carbohydrate in subjects with pre-diabetes on:
DESIGN The investigators plan to conduct 3 investigations. Investigation 1 and 2 are Randomised Crossover Control Trials of 14 days supplementation with 30g of inulin (fermentable carbohydrate) or a cellulose (non fermentable carbohydrate) control to firstly describe the physiology and mechanisms behind appetite regulation and glucose homeostasis. Investigation 3 is a Randomised Control Parallel Study of weight loss followed by weight maintenance to assess the efficacy of fermentable carbohydrate to decrease risk of T2DM.
POPULATION Overweight and obese men or women with pre-diabetes.
TREATMENT Participants in the treatment arm in all 3 investigations will consume inulin 3 times per day (total daily dose: 30g). Participants in the placebo arm in all 3 investigations will be taking cellulose 3 times a day (total daily dose: 30g).
DURATION Investigation 1 will last 16 weeks. Investigation 2 will last 18 weeks. Investigation 3 will last 18 weeks.
Type 2 Diabetes (DMT2) is a major health concern in the UK, as it is worldwide. The increased prevalence of DMT2 in the UK is closely linked with the increased prevalence of obesity, with the risk for diabetes estimated to increase by 4.5-9 percent with every kilogram weight gained (1). Pre-diabetes is also associated with an increase in body weight, and is a critical step in the development of T2DM.
Having pre-diabetes also increases the risk for cardiovascular disease. It is thought this is due to the hyperglycaemia and glycaemic variability seen in the pre-diabetic state. Both hyperglycaemia and glycaemic variability are associated with oxidative stress. Oxidative stress is postulated to cause endothelial damage which can lead to cardiovascular disease. Reductions in hyperglycaemia and glycaemic variability may cause a reduction in oxidative stress.
A number of gut hormones - released physiologically in response to food - have been shown to powerfully inhibit human appetite and inhibit food intake and glucose homeostasis (2). Two of these gut hormones, glucagon like peptide-1 (GLP-1) and peptide YY (PYY) are released from the neuroendocrine L-cell in the colon, and have demonstrable appetite suppressive effects in animals and humans (3-6). GLP-1 also improves glycaemic control by stimulating pancreatic B-cells to secrete insulin in a glucose-dependent manner, inhibits glucagon release and reduces hepatic glucose output (7-9). Long-term treatment with GLP-1 agonists has been shown to cause significant weight loss in humans (10).
Work by ourselves and others in rodents have shown that dietary fermentable carbohydrates (FCHOs) can significantly increase circulating PYY and GLP-1 levels while suppressing appetite centres in the hypothalamus (11-12). This results in lower body fat and abdominal fat with no overall effect on weight; however as abdominal fat is an important cardiovascular risk factor in diabetes, this effect is likely to be favourable to health (13-14). In humans, there are a number of short-term studies that report an increase in satiety following consumption of FCHOs (15-16)and a year-long study of children consuming the FCHO inulin showed significant weight loss compared to controls (17). FCHO has also been shown to increase insulin sensitivity, reduce post-prandial blood glucose levels and enhance lipid oxidation in overweight subjects with and without diabetes (18,19), effects that may be mediated by the FCHO induced GLP-1 increase (GLP-1 was not measured in these studies). Even short-term consumption of FCHO in healthy subjects has a similar effect on glycaemic control (20).
Inulin will be used as the FCHO supplement in all 3 investigations. Inulin has no known effect on the small bowel, being fully fermented in the large bowel. Inulin is therefore ideally suited for the investigation of large bowel fermentation on human appetite, glycaemic control and weight maintenance. Test
An oral glucose tolerance test.
A blood sample of 30ml will be taken for full blood count, liver function tests, electrolytes, thyroid function tests, HbA1c, and glucose.
Body weight and height will be recorded.
APPETITE STUDY SESSIONS
Visit 1, 2, 3 & 4 in Investigation 1.
Participants arrive fasted overnight (10 hour fast). After explanation of the procedures and confirmation that the participant is happy to proceed, body weight is recorded.
A cannula is inserted in a forearm vein facilitating blood sampling throughout the day. Two baseline blood samples are withdrawn. Visual analogue scales (VAS) are completed every time a blood sample is drawn. The sampling scheme is presented below. A total of 80ml of blood will taken during investigation 1 appetite study days, and a total of 115ml be withdrawn during each appetite study visit in investigation 3. Visual Analogue scales to assess appetite will be completed each time a blood sample is taken. The Visual Analogue Scale questions include: "How full do you feel right now?" and "How hungry do you feel right now?" and "How much could you eat right now?". They will answer by making a vertical mark on a ten centimetre line anchored with the terms "not at all" and "extremely". Similarly, side-effects such as nausea, sickness, flatulence, bloating, diarrhoea, and general well-being will be assessed.
At time 0, breakfast is served and participants will have 20 minutes to consume the meal. Lunch is served at 240 minutes, and the meal test is served at 440 minutes after the last blood sample is taken.
During the study session, participants will be asked to minimize physical activity. Water is allowed freely, though participants will be requested not to drink less than 10 minutes prior to a blood sample and VAS completion. At 440 minutes, a pre-weighed meal is served. The meal is served in excess and participants are asked to eat until comfortably full. A jug of water is served with the meal and the water intake will also be recorded.
In investigation 3, the study sessions will be shorter, consisting of a breakfast and a meal test at lunch.
ONE TO ONE DIETARY COUNSELLING
In Investigation 3, all participants will receive dietary counselling at weeks 1, 2, 4, and 7. The instruction given to the participants will be individualised based on current weight and energy requirements, consistent with the usual package of care that would be offered within a dietitian clinic. The participants will be instructed to aim for 5% weight loss over 9 weeks.
SUPPLEMENTATION UNDER FREE-LIVING CONDITIONS
The supplement will be provided in sachets (containing 10g portions). During the run-in period the daily intake will gradually be increased to 30g per day over 4 weeks. During this run-in period the investigators will contact the participants via e-mail or telephone twice to ensure the fibre supplementation has no un-toward side-effects and ensure that instructions are followed and answer any questions the participants may have. The subjects then take 30g a day until the end of the study (at 6 weeks for investigation 1 or 18 weeks in investigation 3).
In investigations 1 and 2 there will be a wash out period of 4 weeks before the subject crosses over the the alternate supplementation.
DIETARY RECORDS, APPETITE AND SIDE-EFFECTS
A 3-day dietary record is to be completed for the 3 days preceding visits 1, 2 and 3 during Investigation 1, and visits 1, 6 and 7 during Investigation 3. On the same days, appetite sensation and side-effects will be assessed using visual analogue scales. The Visual Analogue Scale questions include: "How full did you feel after eating meals today?" and "How hungry did you feel between meals today?". They will answer by making a vertical mark on a ten centimetre line anchored with the terms "not at all" and "extremely". Similarly, side-effects such as nausea, sickness, flatulence, bloating, diarrhoea, and general well-being will be assessed.
METHODS FOR ASSESSING INSULIN AND GLUCOSE HOMOSTASIS MEAL TOLERANCE TEST Participant will attend the clinical investigation unit a 12 hour fast. A cannula will be placed in their forearm. Three fasting blood samples will be taken (-30, -15 and 0). A standard test meal of one Kellogg's breakfast bar and an Ensure Plus will be given. Blood will be taken at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180 amd 240 mins. This will be used to calculate Glucose profile, basal insulin response, dynamic phase insulin, static phase insulin sensitivity, DI=Dynamic phase insulin X Static phase insulin, GIP and GLP-1 response.
Free living glucose monitoring: Medtronic iPro Continuous Glucose Monitor will be used to assess 5-day continuous glucose monitoring. 5-day continuous glucose monitoring to assess "free living" glucose homeostasis. This interstitial fluid glucose data will be analysed for mean glucose and glycaemic variability measures including Mean Amplitude Glycaemic Excursions (MAGE), Continuous Overlapping Net Glycaemic Action (CONGA) and risk indices such as Low Blood Glucose Index (LBGI), High Blood Glucose Index (HBGI) and average daily risk ratio (ADRR). For the participant this will mean having a small plastic cannula place in the subcutaneous tissue in their abdomen. The participants will also be required to take 3 finger-prick glucose measurements on 4 successive days while wearing the CGM.
WHOLE BODY MRI SCANNING In investigation 3, whole body anatomical MR scanning will be performed to determine total and regional fat volumes, and magnetic resonance spectroscopy (MRS) performed to measure lipid content in the internal organs, such as liver (IHCL) and muscles (IMCL), such as soleus and tibialis.
Participants will attend the Robert Steiner MRI unit at Hammersmith Hospital after a 10h overnight fast. The study visit will last 1 hour. Participants are asked to refrain from strenuous exercise and drinking alcohol the day before each visit.
Firstly subjects will complete a metal check form. Next subjects will change into hospital clothes and be asked to lie on the trolley in the scanner. Subjects lie supine or prone in the scanner and are automatically moved through the scanner. While in the scanner participants will have access to a buzzer to sound an alarm, and will be able to hear and respond to instructions from the scanning console. Subjects will be in the MRI scanner for up to 1 hour. Scanning will be performed on either the Philips 3.0 Tesla or Philips 1.5 Tesla MR scanners in the Robert Steiner MRI Unit at the Hammersmith Hospital. None of the magnetic resonance imaging techniques to be used employs ionising radiation or intravenous contrast agents. Participants will also have their weight, height, waist and hip circumference recorded with a tape measure.
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Publications *||Guess ND, Caengprasath N, Dornhorst A, Frost GS. Adherence to NICE guidelines on diabetes prevention in the UK: Effect on patient knowledge and perceived risk. Prim Care Diabetes. 2015 Dec;9(6):407-11. doi: 10.1016/j.pcd.2015.04.005. Epub 2015 May 13.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||August 2014|
|Primary Completion Date||August 2013 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United Kingdom|
|Removed Location Countries|
|NCT Number ICMJE||NCT01841073|
|Other Study ID Numbers ICMJE||FermCarb|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||
|Responsible Party||Imperial College London|
|Study Sponsor ICMJE||Imperial College London|
|Collaborators ICMJE||Not Provided|
|PRS Account||Imperial College London|
|Verification Date||April 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP