Direct Measurement of Microstructure of Ingestive Behaviour After Initiation of GLP-1 Receptor Agonist Treatment at Maximum Dose (DIGRAT)

NCT07457424 | Active Not Recruiting

• 1 other identifier: RS21-065
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolic Disease; Obesity & Overweight

Keywords

eating behaviour; appetite; gut hormones; microstructure of the ingestive behaviour; Behavioural phenotyping; GLP-1 receptor agonist; Semaglutide

Outcome Measures

Primary Outcomes (15)

• Energy Intake from Liquid Meal Consumption

  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).

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Macrostructure of Ingestive Behaviour (Rate of Energy Intake)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Macrostructure of Ingestive Behaviour (Meal Duration)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Macrostructure of Ingestive Behaviour (Number of Sucks)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Suck Energy Intake)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Suck Duration)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Suck Rate)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Suck Maximal Rate)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Burst Number)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Burst Duration)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Burst Energy Intake)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Burst Rate)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behavior (Number of Sucks per Burst)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Inter-Burst Intervals)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

• Microstructure of Ingestive Behaviour (Inter-Sucks Intervals)

  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.

  At baseline, 4 weeks, 12 weeks, 24 weeks, 52 weeks

Secondary Outcomes (14)

• 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)

• 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)

• 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)

• 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)

• 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)

Study Arms (3)

Treatment group

Subjects with obesity (BMI\>30) who are starting Glucagon-like peptide analogs medicine for obesity treatment

Drug: semaglutide 1 mg weekly injection

Control with normal weight

Healthy subjects with normal BMI value

Control with obesity

Study population with obesity not undergoing any treatment

Interventions

semaglutide 1 mg weekly injection DRUG

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.

Also known as: Ozempic

Treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

People with BM\>30 who are started GLP-1 for treating obesity and people with BMI\>30 without using internal weight loss measures and no history of GLP-1 analog. Also, healthy people with BMI\>18.5 and \<24.9 are involved in the study.

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University College Dublin: lead
• University of Zurich: collaborator

Study Sites (1)

Clinical Research Centre

Dublin, Dublin, Dublin 4, Ireland

Location

Related Publications (11)

• Serra M, File B, Alceste D, Raguz I, Gero D, Thalheimer A, Widmer J, Ismaeil A, Steinert RE, Spector AC, Bueter M. Burst-pause criterion derivation for drinkometer measurements of ingestive behavior. MethodsX. 2022 May 11;9:101726. doi: 10.1016/j.mex.2022.101726. eCollection 2022.

  PMID: 35620756 BACKGROUND

• Zoh RS, Esteves BH, Yu X, Fairchild AJ, Vazquez AI, Chapple AG, Brown AW, George B, Gordon D, Landsittel D, Gadbury GL, Pavela G, de Los Campos G, Mestre LM, Allison DB. Design, analysis, and interpretation of treatment response heterogeneity in personalized nutrition and obesity treatment research. Obes Rev. 2023 Dec;24(12):e13635. doi: 10.1111/obr.13635. Epub 2023 Sep 4.

  PMID: 37667550 BACKGROUND

• Chou T, Hoover AW, Goldstein SP, Greco-Henderson D, Martin CK, Raynor HA, Muth ER, Thomas JG. An explanation for the accuracy of sensor-based measures of energy intake: Amount of food consumed matters more than dietary composition. Appetite. 2024 Mar 1;194:107176. doi: 10.1016/j.appet.2023.107176. Epub 2023 Dec 27.

  PMID: 38154576 BACKGROUND

• Gero D, File B, Alceste D, Frick LD, Serra M, Ismaeil AE, Steinert RE, Spector AC, Bueter M. Microstructural changes in human ingestive behavior after Roux-en-Y gastric bypass during liquid meals. JCI Insight. 2021 Aug 9;6(15):e136842. doi: 10.1172/jci.insight.136842.

  PMID: 34369388 BACKGROUND

• Alceste D, Serra M, Raguz I, Gero D, Thalheimer A, Widmer J, File B, Ismaeil A, Steinert RE, Spector AC, Bueter M. Association between microstructure of ingestive behavior and body weight loss in patients one year after Roux-en-Y gastric bypass. Physiol Behav. 2022 May 1;248:113728. doi: 10.1016/j.physbeh.2022.113728. Epub 2022 Feb 5.

  PMID: 35134394 BACKGROUND

• Kissileff HR. The Universal Eating Monitor (UEM): objective assessment of food intake behavior in the laboratory setting. Int J Obes (Lond). 2022 Jun;46(6):1114-1121. doi: 10.1038/s41366-022-01089-0. Epub 2022 Mar 1.

  PMID: 35233038 BACKGROUND

• Camacho-Barcia L, Giel KE, Jimenez-Murcia S, Alvarez Pitti J, Micali N, Lucas I, Miranda-Olivos R, Munguia L, Tena-Sempere M, Zipfel S, Fernandez-Aranda F. Eating disorders and obesity: bridging clinical, neurobiological, and therapeutic perspectives. Trends Mol Med. 2024 Apr;30(4):361-379. doi: 10.1016/j.molmed.2024.02.007. Epub 2024 Mar 14.

  PMID: 38485648 BACKGROUND

• Berthoud HR, Seeley RJ, Roberts SB. Physiology of Energy Intake in the Weight-Reduced State. Obesity (Silver Spring). 2021 Apr;29 Suppl 1:S25-S30. doi: 10.1002/oby.23080.

  PMID: 33759396 BACKGROUND

• Pitts T, Iceman KE. Deglutition and the Regulation of the Swallow Motor Pattern. Physiology (Bethesda). 2023 Jan 1;38(1):0. doi: 10.1152/physiol.00005.2021. Epub 2022 Aug 23.

  PMID: 35998250 BACKGROUND

• Johansen VBI, Petersen J, Lund J, Mathiesen CV, Fenselau H, Clemmensen C. Brain control of energy homeostasis: Implications for anti-obesity pharmacotherapy. Cell. 2025 Aug 7;188(16):4178-4212. doi: 10.1016/j.cell.2025.06.010.

  PMID: 40780185 BACKGROUND

• Watts AG, Kanoski SE, Sanchez-Watts G, Langhans W. The physiological control of eating: signals, neurons, and networks. Physiol Rev. 2022 Apr 1;102(2):689-813. doi: 10.1152/physrev.00028.2020. Epub 2021 Sep 6.

  PMID: 34486393 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma Blood sample for assessing gut hormones levels

MeSH Terms

Conditions

Metabolic Diseases; Obesity; Overweight; Feeding Behavior

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior, Animal; Behavior

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 9, 2026
• Study Start: February 17, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)