Clinical trial NCT03771690: Individual Variability of Appetite Responses to a Standardised Meal
Official title: A Replicated Crossover Study to Explore Individual Variability of Appetite Responses to a Standardised Meal and Any Moderating Influence of the FTO Gene
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Appetitive Behavior
Obesity
Genetic Predisposition to Disease
Keywords: Appetite
FTO
Ghrelin
Individual variability
Meal intake
Peptide YY
Lead sponsor: Loughborough University
Sponsor class: OTHER
Collaborators: name: Teesside University
First posted: 2018-12-11
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of this study is to examine the interindividual variability of subjective and hormonal appetite responses to a standardised meal in healthy men and explore any moderating influence of the fat mass and obesity associated gene (FTO).

Participants homozygous for the obesity risk A allele (AA) or low risk T allele (TT) of FTO rs9939609 will complete two fasted control and two standardised meal (5025 kJ energy, 47% carbohydrate, 9% protein, 44% fat) conditions in randomised sequences. Ratings of perceived appetite and venous blood samples will be taken before and after the interventions. Interindividual differences in appetite responses and the potential moderating influence of the FTO gene will be examined using bivariate correlations and linear mixed modelling.

Detailed description: Meal ingestion initiates a series of co-ordinated subjective and hormonal appetite responses. However, it is not known whether interindividual variability in appetite exists in response to a standardised meal. A recent approach proposed to quantify individual differences in the intervention response involves quantifying the participant-by-response interaction from replicated intervention and comparator arms. Using this approach (a replicated crossover study), the current study will (1) investigate whether the perceived appetite and appetite-related hormone responses to a standardised meal are reproducible on repeated occasions; (2) examine whether there is true individual variability in appetite responses to a standardised meal; and (3) determine whether the fat mass and obesity associated gene (FTO) moderates the magnitude of appetite responses to a standardised meal.

A total of 18 healthy men will be recruited according to their FTO rs9939609 genotype: 9 homozygous minor allele (AA) and 9 homozygous major allele (TT). Participants will complete four main experimental conditions each separated by an interval of at least three days: two fasted control and two standardised meal conditions. Participants will arrive at the laboratory at 09:00 after a 13 h overnight fast and a cannula will be inserted into an antecubital vein for blood sampling. After 60 min rest, a fasting venous blood sample and rating of perceived appetite will be taken (0 h; 10:00). Participants will rest throughout all four conditions but will be provided with a standardised breakfast meal after the fasting measurements during the two meal conditions. Breakfast will be consumed within 15 min and consist of croissants, butter, chocolate spread, cereal biscuits and milkshake which will provide 5025 kJ energy (47% carbohydrate, 9% protein, 44% fat). Subsequent venous blood samples will be taken at 0.5 h (10:30) and 1 h (11:00), and appetite perceptions will be assessed at 1 h (11:00).

Interindividual differences will be explored by correlating the two sets of response differences between meal and control conditions. Within-participant covariate-adjusted linear mixed models will be used to quantify participant-by-condition and FTO genotype-by-condition interactions.

Eligibility criteria: Inclusion Criteria:

* Homozygous minor allele (AA) or major allele (TT) FTO rs9939609 genotype;
* Non-smoker;
* Weight stable for the previous 3 months.

Exclusion Criteria:

* Heterozygous FTO rs9939609 genotype (i.e., AT);
* Any medical conditions (e.g., diabetes, coagulation or bleeding disorders);
* Taking any medication that might influence appetite, fat metabolism or blood glucose;
* Dieting or restrained eating behaviours;
* Any food allergies.

Primary outcomes:
measure: Acylated ghrelin concentration
timeFrame: 1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))
Secondary outcomes:
measure: Total peptide YY concentration
timeFrame: 1 hour (Plasma samples will be collected at 0 hour (pre) and 1 hour (post))
measure: Insulin concentration
timeFrame: 0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))
measure: Glucose concentration
timeFrame: 0.5 hour (Plasma samples will be collected at 0 hour (pre) and 0.5 hour (post))
measure: Rating of perceived hunger
timeFrame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
measure: Rating of perceived satisfaction
timeFrame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
measure: Rating of perceived fullness
timeFrame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
measure: Rating of perceived prospective food consumption
timeFrame: 1 hour (Visual analogue scales will be completed at 0 hour (pre) and 1 hour (post))
Other outcomes:
Locations:
city: Loughborough
country: United Kingdom
facility: Loughborough University
state: Leicestershire
Study officials:
affiliation: Loughborough University
name: David Stensel
role: PRINCIPAL_INVESTIGATOR
affiliation: Loughborough University
name: Fernanda Reistenbach Goltz
role: PRINCIPAL_INVESTIGATOR
affiliation: Teesside University
name: Greg Atkinson
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goltz FR, Thackray AE, King JA, Dorling JL, Atkinson G, Stensel DJ. Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study. Med Sci Sports Exerc. 2018 Apr;50(4):758-768. doi: 10.1249/MSS.0000000000001504.
citation: Atkinson G, Batterham AM. True and false interindividual differences in the physiological response to an intervention. Exp Physiol. 2015 Jun;100(6):577-88. doi: 10.1113/EP085070. Epub 2015 May 13.
citation: Senn S, Rolfe K, Julious SA. Investigating variability in patient response to treatment--a case study from a replicate cross-over study. Stat Methods Med Res. 2011 Dec;20(6):657-66. doi: 10.1177/0962280210379174. Epub 2010 Aug 25.
citation: Senn S. Mastering variation: variance components and personalised medicine. Stat Med. 2016 Mar 30;35(7):966-77. doi: 10.1002/sim.6739. Epub 2015 Sep 28.
citation: Goltz FR, Thackray AE, Atkinson G, Lolli L, King JA, Dorling JL, Dowejko M, Mastana S, Stensel DJ. True Interindividual Variability Exists in Postprandial Appetite Responses in Healthy Men But Is Not Moderated by the FTO Genotype. J Nutr. 2019 Jul 1;149(7):1159-1169. doi: 10.1093/jn/nxz062.