Gut Hormone LEAP2 in Metabolism and Eating Behaviour: Fixed Meal Testing

NCT06013592 | Recruiting

• 1 other identifier: 23HH8298
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this interventional study is to measure the blood levels of the gut hormones LEAP2 and acyl ghrelin (AG), appetite and food intake after consuming liquid meals of different caloric sizes, in healthy adults with and without obesity. AG is a stomach-derived homone that increases appetite, and LEAP2 a liver-gut derived hormone that decreases appetite, which interferes the action of AG ant its receptor in the brain called the growth hormone secretagogue receptor (GHSR). Blood levels of AG and LEAP2 change in opposite directions after food intake (AG decreasing, LEAP2 increasing). AG is formed from an inactive version of hormone called desacyl ghrelin (DAG). Previous studies have shown that greater food intake leads to a greater decrease in blood levels of total ghrelin (AG + DAG), but this has not been studied for changes in blood AG or LEAP2 after eating. Blood levels of AG and total ghrelin when fasted and after food intake are lower, while blood levels of LEAP2 are higher, in adults with than those without obesity. The main study questions are:

1. 1.Are there greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG after consuming larger meals (by amount of calories they contain)?
2. 2.Are greater decreases in appetite after connsuming larger meals related to greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG?
3. 3.Are greater decreases in food intake at a buffet lunch after consuming larger meals eaten a few hours previously related to greater increases in blood levels of LEAP2 and greater decreases in blood levels of AG?
4. 4.Do the above findings differ between adults without obesity and with obesity?

Conditions

Eating Behavior; Obesity; Appetitive Behavior

Keywords

LEAP2; ghrelin; appetite; food intake; eating behaviour

Outcome Measures

Primary Outcomes (2)

• Post-prandial plasma concentration acyl ghrelin

  Incremental area under curve (iAUC) 0-180 minutes, units: pg/mL.hr

  0, 30, 60, 120, 180 minutes

• Post-prandial plasma concentration LEAP2

  Incremental area under curve (iAUC) 0-180 minutes, units: ng/mL.hr

  0, 30, 60, 120, 180 minutes

Secondary Outcomes (2)

• Visual analogue scale ratings of appetite

  0, 30, 60, 120, 180 minutes

• Ad libitum food intake

  at 180 minutes

Study Arms (2)

Healthy adults without obesity

EXPERIMENTAL

Liquid meals with different caloric sizes (0, 600, 900, 1200 kcal) in within-participant cross-over design

Dietary Supplement: 0 kcal liquid meal; Dietary Supplement: 600 kcal liquid meal; Dietary Supplement: 900 kcal liquid meal (only for group without obesity); Dietary Supplement: 1200 kcal liquid meal

Healthy adults with obesity

EXPERIMENTAL

Liquid meals with different caloric sizes (0, 600, 1200, 1800 kcal) in within-participant cross-over design

Dietary Supplement: 0 kcal liquid meal; Dietary Supplement: 600 kcal liquid meal; Dietary Supplement: 1200 kcal liquid meal; Dietary Supplement: 1800 kcal liquid meal (only for group with obesity)

Interventions

0 kcal liquid meal DIETARY_SUPPLEMENT

Flavoured water, given as one meal at one study visit only

Healthy adults with obesity; Healthy adults without obesity

600 kcal liquid meal DIETARY_SUPPLEMENT

Fortisip Compact Vanilla, given as one meal at one study visit only

Healthy adults with obesity; Healthy adults without obesity

900 kcal liquid meal (only for group without obesity) DIETARY_SUPPLEMENT

Fortisip Compact Vanilla, given as one meal at one study visit only

Healthy adults without obesity

1200 kcal liquid meal DIETARY_SUPPLEMENT

Fortisip Compact Vanilla, given as one meal at one study visit only

Healthy adults with obesity; Healthy adults without obesity

1800 kcal liquid meal (only for group with obesity) DIETARY_SUPPLEMENT

Fortisip Compact Vanilla, given as one meal at one study visit only

Healthy adults with obesity

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female between the ages of 18 and 60 years;
• Without obesity with body mass index (BMI) 18.0-29.9 kg/m2 or with obesity with BMI 30.0-50.0 kg/m2;
• Healthy as determined by medical history and vital signs;
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form;
• Participant is able to read, comprehend and record information written in English.

You may not qualify if:

• History of, or current abuse or dependence on alcohol or drugs;
• Current smoker or less than 2 years since quitting (cigarette, cigars, e-cigarettes) or use of nicotine replacement therapy;
• Significant current or past medical or psychiatric history that, in the opinion of the investigators, contraindicates their participation;
• History of type 1 or type 2 diabetes mellitus;
• History of ischaemic heart disease, heart failure, cardiac arrhythmia, peripheral vascular, cerebrovascular disease or uncontrolled hypertension;
• Current diagnosis of anaemia or iron deficiency;
• Body weight instability (change in body weight of more than 5% over the preceding 3 months);
• Use of current regular prescription or over-the-counter medications that in the opinion of the Investigators may affect participant safety or outcome measures;
• Clinically significant abnormalities in screening blood tests abnormalities which in the opinion of the study physician, is clinically significant e.g. diabetes mellitus, hypothyroidism, renal impairment, abnormal liver function tests \[bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)\] \>3x upper limit of normal, other than due to fatty liver disease; Current pregnancy or breast-feeding in female volunteers (the Investigators will recommend using contraception for the duration of the visits to avoid participant drop-out);
• Pulse rate \<40 or \>100 beats per minute OR systolic blood pressure \>160 and \<100 OR diastolic blood pressure \>95 and \<50 in the semi-supine position;
• Volunteer has participated in a clinical trial and has received an investigational product within the following time period prior to the first experimental visit in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer);
• Exposure to more than 3 new investigational medicinal products within 12 months prior to the scan;
• Vegan, gluten or lactose-intolerant (as test meals in the paradigms may include animal products, dairy and wheat products);
• Volunteers who have donated, or intend to donate, blood within three months before the screening visit or following study visit completion;
• Known history of SARS-CoV-2 infection (Covid-19) in the last 4 weeks;

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

PsychoNeuroEndocrinology Research Group, Division of Psychiatry, Dept. of Brain Sciences, Imperial College London

London, W12 0NN, United Kingdom

RECRUITING

MeSH Terms

Conditions

Feeding Behavior; Obesity; Appetitive Behavior

Interventions

Single Person; Population Groups; Adiposity

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Marital Status; Family Characteristics; Demography; Population Characteristics; Socioeconomic Factors; Body Fat Distribution; Body Weights and Measures; Body Constitution; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Body Composition; Biochemical Phenomena; Chemical Phenomena; Metabolism; Physiological Phenomena

Study Officials

• Tony Goldstone, MRCP PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tony Goldstone, MRCP PhD

CONTACT

+44 20 7594 5989; tony.goldstone@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: single-blinded, randomized order
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: within participant

Study Record Dates

• First Submitted: August 22, 2023
• First Posted: August 28, 2023
• Study Start: August 29, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

GB (1)