Clinical trial NCT06538948: Direct Measurement of Ingestive Behaviour in Relation to Sex Differences and Gastrointestinal Hormone Levels in Patients After Metabolic and Bariatric Surgery
Official title: Direct Measurement of Ingestive Behaviour in Relation to Sex Differences and Gastrointestinal Hormone Levels in Patients After Metabolic and Bariatric Surgery
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obesity
Keywords: Obesity
Ingestive Behaviour
Bariatric Surgery
Gut Hormones
Drinkometer
Lead sponsor: University of Zurich
Sponsor class: OTHER
Collaborators: name: Florida State University
name: University College Dublin
First posted: 2024-08-06
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Participants with obesity and scheduled for bariatric surgery are recruited consecutively at the outpatient clinic of bariatric surgery at the University Hospital Zurich.

Participants with obesity not scheduled for surgery are recruited at the private clinic "Adimed" in Winterthur.

Participants without obesity are recruited from students, employees and faculty of the Faculty of Medicine of the University of Zurich.

Brief summary: Bariatric surgery (BS), especially procedures like Sleeve Gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), is the most effective treatment for obesity. Yet, the exact mechanisms governing its effect are somewhat elusive, with current research mainly focusing on post-operative food intake outcomes based on self-reported data, which might not fully capture the nuanced changes in eating behaviours.

To address these gaps, our study plans to employ the newly developed "drinkometer", a device capable of analysing the intricate changes in drinking behaviour following BS. This tool promises to bring a more detailed perspective to the changes in ingestive behaviours, bypassing the inaccuracies of self-reporting methods. By expanding our research to encompass diverse patient demographics and examining potential links to physiological shifts like gut hormone level alterations, the study aims to provide a more rounded understanding of the long-term impacts of BS on eating behaviours.

Detailed description: HYPOTHESIS AND PRIMARY OBJECTIVE

So far, studies of ingestive behaviour in humans have produced ambiguous results. Moreover, direct measurements of ingestive behaviour in humans after BS are still rare and the roles of sex and gut hormones, as well as their relevance for clinical outcome parameters, such as body weight loss, remain elusive. A comprehensive understanding of how a given intervention such as BS affects food intake requires a detailed analysis of the ingestive behaviour itself, not simply the measurement of the outcome of the behaviour. In other words, the information on how the food is consumed is equally or even more important than the information on how much food has been ingested.

This study employs the drinkometer methodology to perform direct measurements of ingestive behaviour in male and female human patients after SG and RYGB along with parallel measurements of postprandial gut hormone levels. Furthermore, this study investigates the clinical relevance of changes in ingestive behaviour by correlating microstructural parameters with body weight loss in a consecutive set of patients who received RYGB at the University Hospital Zurich five years before the time of recruitment.

Of note, the proposed experiments aim to test specific hypotheses regarding the behavioural mechanisms underlying potential changes in food intake after BS in humans. Thus, this research do not aim to identify how BS affects one or the other single microstructural parameters of eating or drinking. Instead, this study investigates how a given intervention that is known to substantially affect food intake behaviour - such as BS - alters the profile of a group of microstructural parameters of ingestive behaviour in humans. Given that ingestive behaviour represents the readout of the central nervous system mechanisms controlling energy intake (e.g., palatability, aversion, avoidance, satiation), the results of the proposed studies will inform the search for the underlying neural circuits in the brain that are specifically altered by BS. If there is no altered behaviour, there would be no point in investigating the underlying physiology. More specifically, this study aims to:

1. Investigate longitudinal changes and differences in the ingestive behaviour of female patients before and within one year after either primary RYGB or primary SG (Study 1).
2. Investigate a possible association between the ingestive behaviour and the prandial gut hormone levels of female patients before and within one year after either primary RYGB or SG (Study 1).
3. Investigate a possible difference between the ingestive behaviour of female and male patients before and within one year after primary RYGB (Study 2).
4. Investigate a possible association between the postoperatively achieved body weight loss of female and male patients 5 years after primary RYGB and ingestive behaviour (Study 3).
5. Investigate, in a subset of responders and non-responders to primary RYGB, a possible association between postprandial gut hormone levels of female and male patients 5 years after primary RYGB and ingestive behaviour (Study 3).

PRIMARY AND SECONDARY ENDPOINTS

In the research protocol, the primary and secondary outcomes specific to each of the three studies planned within the research project have been described. Recognising that each study has its unique objectives and hypotheses, the outcomes have been specified distinctly for each study to ensure clarity and focus in the research approach.

For each of the three studies, the primary outcomes are those key results that the study is primarily designed to assess. These are the main effects or findings that are anticipated to provide the most significant insights into the research questions. Secondary outcomes, while still important, are additional results that can be explored after answering the main research questions. These might provide supplementary information, support the primary outcomes, or offer insights into other areas related to the main research question.

By presenting these outcomes separately for each study, this study aims to provide a structured and transparent overview of the research intentions, allowing for a clear understanding of the objectives and measures in each specific part of the project. This approach not only aids in maintaining the focus and integrity of each study but also assists in the clear communication of the research goals and methods.

PROJECT DESIGN

The proposed studies will test key elements of ingestive behaviour and their relation to pre- and postprandial levels of gut hormones as well as sex differences after the two most frequently performed bariatric operations. They will thus provide useful information for planning and conducting future trials in the field, such as optimal recruitment and retention strategies, intervention delivery, data collection methods and adherence to study protocols. The proposed studies will further provide empirical estimates of effect sizes of bariatric surgery and long-term associations of ingestive behaviour with gut hormones for post-bariatric body weight loss. The potential outcomes of Studies 1, 2 and 3 are conceptually different. Nevertheless, the results of these studies will complement each other as well as our findings from previous studies, and can be used to calculate sample sizes for future trials.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 year
* BMI ≥ 35 kg/m2 for patients with planned RYGB or SG operation
* BMI ≥ 30 kg/m2 for external controls affected by obesity but no planned RYGB or SG within the next 12 months, and
* BMI ≥ 18.5 kg/m2 and ≤ 24.9 kg/m2 for controls without obesity.

Exclusion Criteria:

* history of previous bariatric operations and/ or revisional surgery (e.g., alteration of limb lengths after primary RYGB),
* smoking,
* established diagnosis of type 1 or 2 diabetes mellitus, and
* polycystic ovary syndrome (PCOS).

Primary outcomes:
measure: Drinkometer Measurement of Microstructural Parameters of Ingestive Behaviour, such as Suck Energy Intake and Burst Energy Intake.
timeFrame: One year after bariatric surgery
measure: Effect of the Gut Hormones in Plasma on the Microstructural Parameters of Ingestive Behaviour Measured with the Drinkometer Device
timeFrame: One year after bariatric surgery
measure: Effect of Biological Sex (Male or Female) on the Microstructural Parameters of Ingestive Behaviour Measured with the Drinkometer Device
timeFrame: One year after bariatric surgery
measure: Cluster identification
timeFrame: Five years after bariatric surgery
measure: Correlation of Percentage Excess Body Mass Index Loss with the Microstructural Parameters of Ingestive Behaviour Measured with the Drinkometer Device Five Years After Roux-en-Y Gastric Bypass Surgery
timeFrame: Five years after bariatric surgery
Secondary outcomes:
Other outcomes:
Locations:
city: Männedorf
country: Switzerland
facility: Hospital Männedorf
state: Zurich
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Department of Surgery and Transplantation
Study officials:
affiliation: University of Zurich
name: Marco Bueter, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gero D, Steinert RE, le Roux CW, Bueter M. Do Food Preferences Change After Bariatric Surgery? Curr Atheroscler Rep. 2017 Sep;19(9):38. doi: 10.1007/s11883-017-0674-x.
citation: le Roux CW, Bueter M. The physiology of altered eating behaviour after Roux-en-Y gastric bypass. Exp Physiol. 2014 Sep;99(9):1128-32. doi: 10.1113/expphysiol.2014.078378.
citation: 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.
citation: 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.
citation: Lutz TA, Bueter M. Physiological mechanisms behind Roux-en-Y gastric bypass surgery. Dig Surg. 2014;31(1):13-24. doi: 10.1159/000354319. Epub 2014 May 8.
citation: Gero D, File B, Justiz J, Steinert RE, Frick L, Spector AC, Bueter M. Drinking microstructure in humans: A proof of concept study of a novel drinkometer in healthy adults. Appetite. 2019 Feb 1;133:47-60. doi: 10.1016/j.appet.2018.08.012. Epub 2018 Sep 1.
citation: 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.