Metabolic Disease, Obesity & Overweight
Conditions
Keywords
eating behaviour, appetite, gut hormones, microstructure of the ingestive behaviour, Behavioural phenotyping, GLP-1 receptor agonist, Semaglutide
Brief summary
Ingestion of food instigates the release of a battery of enteroendocrine peptide hormones that help control gut motility and digestive secretion. Peptide hormone products of the enteroendocrine L-cell and GLP-1 in particular, play multiple roles in relation to the regulation of pancreatic islet function and gastric emptying and the induction of satiety pathways in the central nervous system The mechanism of action of GLP-1 RAs on food intake reduction is mainly mediated through both peripheral and central nervous system (CNS) pathways. GLP-1 RAs directly stimulates POMC neurons and inhibits neuropeptide-Y (NPY) and Agouti-related peptide (AgRP) neurons in the arcuate nucleus resulting in a reduction in hunger and increases in fullness4. While there were studies which indirectly measured the changes of food preference and eating behaviour in humans after using GLP-1 RAs via visual analogue scales (VAS) or Patient's Experiences Questionnaires the investigators found there is a necessity to conduct the studies to do direct measurements of the changes of food preference and eating behaviour. Direct measures of an altered food selection in humans after using GLP-1 RAs have virtually not been performed likely due to the significant methodological and conceptual challenges they pose to researchers and study design. However, direct measures represent an essential component in the attempt to understand how GLP-1 RAs alters eating and diet selection which is the main reason of conducting this study. This innovative experiment will be a critical and a novel test of the explicit experience of humans with high-sugar high-fat fluids after using GLP-1 RAs and its potential role for the understanding of possible mechanisms determining post-treatment outcome such as weight loss.
Detailed description
Food intake results in the feeling of fullness, but different foods with the same energy value may induce a variable amount of fullness. Many of the satiety signals come from the lower part of the small intestine where satiety hormones are released. Obesity is associated with impaired metabolic pathways along with disordered signalling of appetite, hence individuals with obesity experience symptoms that manifest as an increase in hunger and lack of fullness. Thus, using analogues of our natural satiety/fullness hormones in individuals with obesity can suppress excessive hunger and increase fullness via slowing down gastric emptying, increasing secretion of insulin and satiety hormones and affecting on Brain-Gut axis which leads to less calorie intake and weight loss. In this study, the investigators want to review the changes in the microstructure of ingestive behaviour of participants after using the maximum dose of an obesity management medication which is similar to our natural satiety hormone via a specific device named drinkometer allowing real-time measurement of subjects' intake rate and total volume intake of one standardised liquid meal. The drinkometer device consists of an electronic scale on which a container with the liquid meal is set at each study visit in the Clinical Research Centre of St. Vincent's University Hospital. Guidance, fixed to a casing around the balance container system, delivers a tube close to the bottom of the container. The other end of the opaque tube extends to the subject and allows the sampling of the liquid meal via a mouthpiece. The tube, mouthpiece and liquid container are biocompatible and food safe. The participants will attend five visits in total including 1) Pre-Intervention site visit, 2) 4 weeks after initiation of the treatment, 3) at 12 weeks, when maximum dose is reached, 4) 26 weeks after initiation, still at maximum dose, 5) 52 weeks after initiation, still at maximum dose. The primary objective of the study is to use an analysis of ingestive behaviour to test the hypothesis that using a maximum dose of a GLP-1 receptor agonist medication changes the microstructure of the ingestive behaviour with specific patterns that can be used for behavioural phenotyping and therefore, treatment decision and prediction of the clinical outcomes.
Interventions
DRUGsemaglutide 1 mg weekly injection
Initiation of semaglutide treatment with weekly injection. The patient starts at 0.25 mg for 4 weeks and then the dose escalates at 0.5 mg. The maximum dose of 1 mg is reached at week 12. The patients decided to undergo the treatment before they were recruited in the study.
Sponsors
University College Dublin
University of Zurich
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 75 * Treatment Group: BMI \> 30 kg/m2 and clinically indicated for GLP-1 RA's treatment. * Controls with obesity (BMI ≥ 30 kg/m2) with no history of GLP-1 RA's treatment. * Healthy normal weight controls (BMI \< 25 kg/m2) with no history of using GLP-1 RAs * Independently mobile * Capacity to consent to participate
Exclusion criteria
* Pre-treatment factors impairing the ability to consume meal such as Significant dysphagia * Gastric outlet obstruction * Systemic or gastrointestinal condition which may affect food intake or preference * Pregnancy or lactation (At the beginning of each study visit, a urine pregnancy test will be performed for all female participants). * Active and significant psychiatric illness including substance misuse * Significant cognitive or communication issues * Medications with documented effects on food intake or food preference * History of significant food allergy and certain dietary restrictions (except for lactose intolerance)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Energy Intake from Liquid Meal Consumption | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Total energy intake (in kilocalories) from consumption of high-carbohydrate, high-sucrose, and high-fat lactose-free milk during each visit. Intake is measured using a drinkometer device that quantifies the exact volume consumed, which is then converted into kilocalories based on the known energy density of each meal type. The unit of measure is kilocalories (kcal). |
| Macrostructure of Ingestive Behaviour (Rate of Energy Intake) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | The rate of energy intake is calculated for each participant during the ingestion of each of the one stimuli, based on standardised measurements from the drinkometer system. This measure reflects the average caloric intake per second over the course of the test stimulus consumption. Energy intake is determined by the volume of liquid consumed, multiplied by the known caloric density of the test stimulus, and divided by the duration of the ingestion period. The unit of measure is kilocalories per second (kcal/s). This outcome is assessed during the five study visits, in which a one test stimulus is administered at each visit. |
| Macrostructure of Ingestive Behaviour (Meal Duration) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Meal duration is defined as the total time taken by each participant to consume the liquid meal, measured using the standardised drinkometer system. The duration is recorded from the initiation of ingestion (first measurable suck) to the completion of consumption (last measurable suck). The unit of measure is seconds (s). This outcome is assessed during the five study visits. The test stimuli are offered to participants simultaneously. |
| Macrostructure of Ingestive Behaviour (Number of Sucks) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | The primary outcome is the number of sucks performed by each participant during the ingestion of the liquid meal as measured using a standardised drinkometer system. A "suck" is defined as a discrete negative pressure event generated by the participant to draw in liquid, as detected by the drinkometer's calibrated weight sensors. For the stimulus, the total number of sucks is recorded as a simple count, with the unit of measure being "number (n)." The outcome is assessed at each of the five study visits, each of which features a single test stimulus administered in a standardised fashion. |
| Microstructure of Ingestive Behaviour (Suck Energy Intake) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Suck energy intake is defined as the total amount of energy (in kilocalories) consumed by the participant during each individual suck, measured for test stimuli using a standardised drinkometer system. For each test stimulus, the total caloric intake is calculated by multiplying the volume of liquid ingested by its caloric density and summing the values across all measured sucks. The unit of measure is kilocalories (kcal). This outcome is assessed during the five study visits, test stimuli are presented to the participant simultaneously. |
| Microstructure of Ingestive Behaviour (Suck Duration) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Suck duration is defined as the time span of each individual suck performed by the participant during the ingestion the liquid meal test stimuli, as measured by a standardised drinkometer system. For each test stimulus, the duration of every suck is recorded from the initiation to the completion of the negative pressure event. The unit of measure is seconds (s). This outcome is assessed during the five study visits, where the stimulus of the liquid meal is administered at each visit. The test stimuli are presented simultaneously. |
| Microstructure of Ingestive Behaviour (Suck Rate) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Suck rate is defined as the average energy intake of liquid ingested per second during each suck, measured for the test stimuli using a standardised drinkometer system. The energy intake consumed during each suck is divided by the corresponding suck duration to determine the rate of ingestion for that event. The unit of measure is kilocalories per second (kcal/s). This outcome is assessed during the five study visits, where the single test stimulus is administered at each visit. The test stimuli are presented simultaneously. |
| Microstructure of Ingestive Behaviour (Suck Maximal Rate) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Suck maximal rate is defined as the highest instantaneous rate of liquid ingestion (in kilocalories per second) achieved during any single suck by the participant for the test stimuli, as measured using a standardised drinkometer system. For the test stimulus, the maximal rate is determined by identifying the suck with the greatest energy intake per unit time among all measured sucks during the ingestion period. The unit of measure is kilocalories per second (kcal/s). This outcome is assessed during the five study visits where the stimuli are presented simultaneously. |
| Microstructure of Ingestive Behaviour (Burst Number) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Burst number is defined as the total count of distinct bursts performed by the participant during the ingestion of the stimuli, as measured using a standardised drinkometer system. A "burst" is operationally defined as a sequence of successive sucks separated by brief pauses, typically reflecting a rhythmic drinking pattern. For the stimulus, the number of such bursts is recorded as an integer value. The unit of measure is "number of bursts" (n). This outcome is assessed during the five study visits, where the test stimuli is presented simultaneously. |
| Microstructure of Ingestive Behaviour (Burst Duration) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Burst duration is defined as the total elapsed time of each individual burst performed by the participant during the ingestion of the test stimuli, as measured using a standardised drinkometer system. A "burst" is operationally defined as a sequence of consecutive sucks separated by brief pauses. For each burst, the duration is measured from the onset of the first suck to the end of the last suck within the burst. The unit of measure is seconds (s). This outcome is assessed during the five study visits, where the test stimulus is presented simultaneously. |
| Microstructure of Ingestive Behaviour (Burst Energy Intake) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Burst energy intake is defined as the total amount of energy intake (in kilocalories) consumed during each individual burst by the participant, measured for the test stimuli using a standardised drinkometer system. A "burst" is operationally defined as a sequence of consecutive sucks separated by brief pauses. For each burst, the energy intake is calculated by multiplying the volume of liquid ingested within the burst by the energy density of the test stimulus. The unit of measure is kilocalories (kcal). This outcome is assessed during the five study visits, where the test stimuli is offered simultaneously. |
| Microstructure of Ingestive Behaviour (Burst Rate) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Burst rate is defined as the average rate of energy intake during each individual burst performed by the participant for the test stimuli, as measured using a standardised drinkometer system. For each burst, the total energy intake (in kilocalories) is divided by the duration of the burst (in seconds) to determine the average rate of energy intake for that burst. The unit of measure is kilocalories per second (kcal/s). This outcome is assessed during the five study visits, where the test stimuli are offered simultaneously. |
| Microstructure of Ingestive Behavior (Number of Sucks per Burst) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | The number of sucks per burst is defined as the average count of individual sucks occurring within each burst during the ingestion of the test stimuli, as measured using a standardised drinkometer system. A "burst" is operationally defined as a sequence of consecutive sucks separated by brief pauses. For each burst, the total number of sucks is recorded, and the outcome is typically reported as the mean number of sucks per burst. The unit of measure is "number of sucks per burst" (n). This outcome is assessed during the five study visits, where the test stimuli are presented simultaneously. |
| Microstructure of Ingestive Behaviour (Inter-Burst Intervals) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Inter-burst interval is defined as the elapsed time between the end of one burst and the onset of the subsequent burst during the ingestion of the test stimuli, as measured using a standardised drinkometer system. A "burst" is operationally defined as a sequence of consecutive sucks separated by brief pauses. The inter-burst interval quantifies the temporal spacing between bursts and is recorded in seconds (s). This outcome is assessed during the five study visits, the stimulus is offered simultaneously. |
| Microstructure of Ingestive Behaviour (Inter-Sucks Intervals) | At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks | Inter-suck interval is defined as the elapsed time between the end of one suck and the initiation of the subsequent suck during the ingestion of each of the test stimulus, as measured using a standardised drinkometer system. A "suck" is operationally defined as a discrete negative pressure event corresponding to the drawing in of liquid. The inter-suck interval quantifies the temporal spacing between individual sucks within a burst or throughout the test stimulus consumption, and is recorded in seconds (s). This outcome is assessed during the five study visits, where the test stimulus is presented simultaneously. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective Appetite Sensation: Desire To Eat | Measured at 3 time points per visit: before the drinkometer test, directly at the end of the drinkometer test, and 30 minutes after the end of the drinkometer test. | Self-reported desire to eat is assessed using a 100 mm Visual Analogue Scale (VAS) ranging from 0 mm, 'no desire to eat at all', to 100 mm, 'extreme desire to eat'. Higher scores indicate the greater desire to eat. Unit of measure: millimeters (mm). |
| Subjective Appetite Sensation: Nausea | Measured at 3 time points per visit: before the drinkometer test, directly at the end of the drinkometer test, and 30 minutes after the end of the drinkometer test. | Self-reported nausea is assessed using a 100 mm Visual Analogue Scale (VAS) ranging from 0 mm, 'not nauseous at all', to 100 mm, 'extremely nauseous'. Higher scores indicate greater nausea. Unit of measure: millimeters (mm). |
| Subjective Appetite Sensation: Abdominal Discomfort | Measured at 3 time points per visit: before the drinkometer test, directly at the end of the drinkometer test, and 30 minutes after the end of the drinkometer test. | Self-reported abdominal discomfort is assessed using a 100 mm Visual Analogue Scale (VAS) ranging from 0 mm, 'no abdominal discomfort at all', to 100 mm, 'extreme abdominal discomfort'. Higher scores indicate greater abdominal discomfort. Unit of measure: millimeters (mm). |
| Plasma GLP-1 Concentration | GLP-1 concentrations are measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in GLP-1 concentration (pmol/L) 30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma GIP Concentration | GIP concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in GIP concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma Amylin Concentration | Amylin concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in amylin concentration (pmol/L) post-liquid meal drink ( 30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma PYY Concentration | PYY concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in PYY concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma Ghrelin Concentration | Ghrelin concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in ghrelin concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma Leptin Concentration | Leptin concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in leptin concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma Insulin Concentration | Insulin concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | Change in insulin concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Plasma CCK Concentration | CCK concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52) | CCK concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion), across the three meal types. Unit of measure is picomoles per liter (pmol/L). |
| Plasma Glucagon Concentration | Glucagon concentrations were measured 30 minutes after ingestion of the liquid meal at each study visit (baseline and weeks 4, 12, 24, and 52 | Change in glucagon concentration (pmol/L) post-liquid meal drink (30 minutes after ingestion). Unit of measure is picomoles per liter (pmol/L). |
| Subjective Appetite Sensation: Hunger | Measured at 3 time points per visit: before the drinkometer test, directly after the drinkometer test, and 30 minutes after the end of the drinkometer test. | Self-reported hunger is assessed using a 100 mm Visual Analogue Scale (VAS) ranging from 0 mm, 'not hungry at all', to 100 mm, 'extremely hungry'. Higher scores indicate greater hunger. Unit of measure: millimeters (mm). |
| Subjective Appetite Sensation: Fullness | Measured at 3 time points per visit: before the drinkometer test, directly at the end of the drinkometer test, and 30 minutes after the end of the drinkometer test. | Self-reported fullness is assessed using a 100 mm Visual Analogue Scale (VAS) ranging from 0 mm, 'not full at all', to 100 mm, 'extremely full'. Higher scores indicate greater fullness. Unit of measure: millimeters (mm). |
Countries
Ireland
Outcome results
None listed