None listed
Conditions
Brief summary
Obesity has reached epidemic proportions globally and is associated with serious co-morbidities, including type 2 diabetes. Once adipose tissue has been accumulated, and food intake is limited by low calorie diets, counter-regulatory mechanisms induce an increase in appetite and a decrease in energy expenditure, which makes weight loss very difficult to maintain. To combat the global burden of obesity and its co-morbidities, a major challenge lies in the development of effective therapies that increase fullness and satiety, and result in good blood glucose control, while lacking adverse effects that are often associated with current therapies. There is increasing evidence that nutrient stimuli in the gastrointestinal tract play a central role in the control of energy intake and blood glucose. Proteins, and their building blocks, amino acids, are of interest, since high-protein diets are very effective for weight loss, particularly loss of fat, rather than muscle mass, and for improving postprandial glycaemic control, in obese individuals with and without type 2 diabetes. There is some evidence that a number of amino acids (including L-phenylalanine) may also have effects on energy intake, blood glucose and gut function in humans. Thus, they are of special interest in terms of potential therapeutic approaches for obesity and type 2 diabetes. This is an exploratory study and will investigate the dose-related effects of intragastric administration of L-phenylalanine on gastric emptying, gut hormone release, glycaemic control, appetite perceptions and energy intake in healthy, normal weight subjects.
Interventions
This trial is comprised of two study parts:
Part A: Assessment of energy intake,
Part B: Assessment of blood glucose and gastric emptying,
following administration of 0g, 5g, or 10g L-phenyalalanine 30 min prior to a meal (Part A: ad libitum buffet style meal; Part B: standardised Ensure drink meal).
Although it will not be required, subjects will be invited to participate in both parts.
In each of Parts A and B, subjects will receive, in randomized, double-blind fashion, an intragastric bolus
This trial is comprised of two study parts: Part A: Assessment of energy intake, Part B: Assessment of blood glucose and gastric emptying, following administration of 0g, 5g, or 10g L-phenyalalanine 30 min prior to a meal (Part A: ad libitum buffet style meal; Part B: standardised Ensure drink meal). Although it will not be required, subjects will be invited to participate in both parts. In each of Parts A and B, subjects will receive, in randomized, double-blind fashion, an intragastric bolus infusion (100ml) of i) 5g L-phenylalanine; ii) 10g L-phenylalanine; iii) saline (control). Subjects will receive one infusion per visit. Study visits will be separated by 3-7 days. Part A: For each study visit a baseline blood sample, and Visual analogue Scale (VAS) questionnaire will be collected (t = -31) . At t = -31 min the infusion will be administered over 1 minute using a feeding tube. At t = -20, -10, and 0 min, a further blood sample will be collected and VAS completed. At t = 0 min, subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 minutes to freely consume the buffet meal until comfortably full. At t = 30, and 60 min further blood samples will be taken, and VAS administered, Part B: For each study visit a baseline blood sample, VAS, and breath sample will be collected (t = -31). At t = -31 the infusion will be administered over 1 minute using a feeding tube. At t = -20, -10, and -1 min further blood samples will be collected and VAS completed. At t = -1 min, subjects will consume, within 1 minute, a mixed-nutrient drink (Ensure, 400 kcal, 300 ml) labeled with 100 mg of 13C-acetate for measurement of gastric emptying by breath sampling, and 3g 3-OMG for measurement of glucose absorption. Blood samples and VAS will be taken every 15 minutes, and breath samples will be taken every 5 min, over the next hour (t = 0 to 60 min). Over the following hour, VAS and blood samples will be collected every half hour (t = 90, 120), and breath samples collected every 15 min (t = 75, 90, 105, 120).
Sponsors
Christine Feinle-Bisset
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
Male
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
A total of 16 healthy, lean (BMI 19-25 kg/m2) male subjects, aged between 18 - 55 years, will be included in each study part.
Exclusion criteria
Significant gastrointestinal symptoms, disease or surgery; Current gallbladder or pancreatic disease; Cardiovascular or respiratory diseases; Phenylketonuria; . Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above); Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, body weight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.); Individuals with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study; Lactose intolerance/other food allergy(ies); Vegetarians; Current intake of greater than 2 standard drinks on greater than 5 days per week; Current smokers of cigarettes/cigars/marijuana; Current intake of any illicit substance; High performance athletes; Restrained eaters (score >12 on the three factor eating questionnaire); Inability to comprehend study protocol; Unable to tolerate naso-gastric tube.
Outcome results
None listed