Appetitive BehaviorNCT03025347
Effect of Exercise on Appetite, Gut Peptides and Butyrylcholinesterase Activity in Variants of the FTO Gene
A study testing Exercise in people with Appetitive Behavior, run by Loughborough University at 1 site in United Kingdom.
Trial summary
Using a database of individuals with FTO genetic data, the study aims to assess the appetite, energy intake, butyrylcholinesterase, gut hormone responses to a bout of moderate- to high intensity exercise in individuals with genetic variations in the FTO gene. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Appetitive Behavior
- What is being tested?
- Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2014to Dec 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- non-smoker, not currently dieting, weight stable for >3 months (self-reported), no personal history of cardiovascular disease, metabolic disease or dyslipidaemia, European ancestry, no psychiatric or medical condition
Who cannot join
- food allergies, dislike or intolerance of study foods and drinks, irregular eating patterns, use of medication that could influence hormone concentrations
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Exercise on Appetite, Energy Intake, Butyrylcholinesterase Activity and Gut Peptides in Men With Variants of the Obesity-linked FTO rs9939609 Polymorphism
Using a database of individuals with FTO genetic data, the study aims to assess the appetite, energy intake, butyrylcholinesterase, gut hormone responses to a bout of moderate- to high intensity exercise in individuals with genetic variations in the FTO gene.
Read the detailed description
The fat mass and obesity-associated gene (FTO) rs9939609 A allele is related to obesity, greater food intake and impaired postprandial reduction of ghrelin. Exercise acutely suppresses levels of ghrelin and appetite, yet whether the response differs in people with or without the rs9939609 A allele is unknown. This study assessed the effect of exercise on appetite, appetite-regulatory hormones and energy intake in variants of the FTO rs9939609 polymorphism.
Cohort
The investigators initially recruited 202 subjects to a database and measured FTO rs9939609 genotype. From these subjects, 12 individuals homozygous for the 'obesity-risk' rs9939609 A allele and 12 homozygous for the T allele were recruited.
A sample size of 24 was chosen based on previous data which suggested that a 34 pg/ml reduction in circulating acylated ghrelin during exercise could be detected with > 80% power with a two-tailed t-test whilst assuming a standard deviation of differences of 54 pg/ml.
Familiarisation trial
First, participants will arrive for a familiarisation trial. Participants will have been fasted for ~2-3 hours beforehand. Participant's height, weight and skinfold measures will be taken. Furthermore, a food preferences questionnaire will be completed to ensure the acceptability of food items provided during the study.
Participants will complete a sub-maximal fitness test, which will last for 16 minutes, and will comprise of four, four minute stages. Initial treadmill speed will be set according to fitness and will be increased every four minutes by 0.5-1.5 km/h. Prior to this test, participants will be fitted with a cannula into an antecubital vein and a blood sample will be withdrawn after the test. This will familiarise participants with the procedure and reduce any stress related to the novelty of the first visit.
Next, a maximal fitness test will be conducted to measure maximal oxygen uptake. This will consist of an incremental protocol where the treadmill gradient will begin at 3.5% and will be increased by 2.5% every 3 minutes. The speed of treadmill will remain constant, and will be determined based on fitness levels. Though the duration of the test is typically 9-15 minutes, it will last until the participant reaches volitional exhaustion.
After the fitness test and adequate recovery time, participants will be presented with a buffet-style meal and instructed to eat until comfortably full and satisfied. To finish, participants will be given a calibrated set of weighing scales and instructions to standardize their food intake before each main trial.
Main trials
Each participant will complete two main trials separated by 7 days: an exercise trial and control trial. In the 24 hours before a main trial, participants will follow a set of standardization procedures. Participants will record all foods consumed and the timings of meals before the first trial. This will be subsequently replicated in the 24 hours prior to the second main trial. Moreover, participants will visit the lab to be provided with a meal and will be instructed to prepare and consume between 19:00-20:00 the night before each main trial. Participants will also be instructed to refrain from strenuous physical activity and alcohol consumption during this period.
Participants will report to the lab on the morning of each trial at 08:00 following an overnight fast. Participants will be instructed to walk slowly to the lab in the morning of each trial.
At 08:30, a cannula will be inserted into an antecubital vein followed by 60 minutes of rest. On the exercise trial, from 09:30 to 10:30, participants will run at a continuous pace that corresponds to 70% of the participant's maximal oxygen uptake. Participants will rest on the bed during this same period of the control trial. Participants will rest and will be provided with a selection of movies to watch for the rest of the trial.
There will be two meals provided to the participants: a standardised meal and an ad libitum buffet style meal. The standardised meal will be a fixed breakfast meal that participants will be provided at 10:50, and will be instructed to consume within 20 minutes. The ad libitum buffet style meal will be given at 15:50 and will consist of an array of foods with differing energy and macronutrient compositions. Participants will be presented with the buffet foods for 30 minutes and will be instructed to eat until comfortably full and satisfied.
Statistical procedures
Linear mixed model, with factors being trial (exercise or control), genotype (AA or TT) and time will be performed on all time-course measures. Area under the curve will be calculated using the trapezoidal rule for outcome measures taken periodically throughout the day. Linear mixed models will also be used for trial and genotype comparisons of area under the curve values and measures not taken throughout the day. At points of interest, where significant main and interaction effects occur, post-hoc analysis was conducted using Holm-Bonferroni adjusted t-tests. Statistical significance was accepted as P < 0.05.
- Conditions
- Appetitive Behavior
- Being tested
- Control, Exercise
- Medical subject headings
- Appetitive Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ControlOther
Participants complete a resting control condition instead of a run.
ExerciseOther
Participants complete a 60 minute run at 70% of their maximal oxygen uptake
| Study group | Role | What they receive |
|---|---|---|
| Control | Experimental | Experimental day where participants rest. Receives: Other: Control |
| Exercise | Experimental | Experimental day where participants complete a run. Receives: Other: Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma acylated ghrelin concentrations (N=24)
Measured using ELISA from venous blood samples
Measured: 24 hours
Plasma desacyl ghrelin concentrations (N=24)
Measured using ELISA from venous blood samples
Measured: 24 hours
Subjective appetite (N=24)
Measured using visual analogue scales
Measured: 24 hours
Ad-libitum energy intake (N=24)
Measured at laboratory-based meals
Measured: 24 hours
Plasma butyrylcholinesterase activity (N=24)
Measured using Ellman's reagent protocol
Measured: First hour of main trial (three samples).
Secondary outcomes (3)
Plasma total glucagon-like peptide 1 concentrations (N=24)
Measured using ELISA from venous blood samples
Measured: 24 hours
Plasma total peptide yy concentrations (N=24)
Measured using ELISA from venous blood samples
Measured: 24 hours
Plasma leptin concentrations (N=24)
Measured using ELISA from venous blood samples
Measured: Baseline (fasting) sample
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2017 (estimated)
- Study startDec 2014
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Appetitive BehaviorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loughborough University
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London, Rosetrees Trust, National Institute for Health Research, United Kingdom
- Responsible party
- Principal investigator, Professor David Stensel, Loughborough University
- Investigators
- David J Stensel, PhD, Principal investigator, Loughborough University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03025347
- Sponsor's protocol ID
- R14-P143
- Status last verified
- Feb 2019
- First submitted
- 17 Jan 2017
- Last updated
- 7 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. doi: 10.1126/science.1141634. Epub 2007 Apr 12.
PubMed 17434869Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring). 2008 Aug;16(8):1961-5. doi: 10.1038/oby.2008.318. Epub 2008 Jun 12.
PubMed 18551109Karra E, O'Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Ruther UU, Bruning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug;123(8):3539-51. doi: 10.1172/JCI44403. Epub 2013 Jul 15.
PubMed 23867619Dorling JL, Clayton DJ, Jones J, Carter WG, Thackray AE, King JA, Pucci A, Batterham RL, Stensel DJ. A randomized crossover trial assessing the effects of acute exercise on appetite, circulating ghrelin concentrations, and butyrylcholinesterase activity in normal-weight males with variants of the obesity-linked FTO rs9939609 polymorphism. Am J Clin Nutr. 2019 Nov 1;110(5):1055-1066. doi: 10.1093/ajcn/nqz188.
PubMed 31504106
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Exercise on Appetite, Energy Intake, Butyrylcholinesterase Activity and Gut Peptides in Men With Variants of the Obesity-linked FTO rs9939609 Polymorphism
- ClinicalTrials.gov ID
- NCT03025347
- Acronym / sponsor ID
- R14-P143
- Conditions
- Appetitive Behavior
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Loughborough UniversityUniversity, hospital or other
- Collaborators
- University College, London, Rosetrees Trust, National Institute for Health Research, United Kingdom
- Study start
- Dec 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 19 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Using a database of individuals with FTO genetic data, the study aims to assess the appetite, energy intake, butyrylcholinesterase, gut hormone responses to a bout of moderate- to high intensity exercise in individuals with genetic variations in the FTO gene.
Detailed description
The fat mass and obesity-associated gene (FTO) rs9939609 A allele is related to obesity, greater food intake and impaired postprandial reduction of ghrelin. Exercise acutely suppresses levels of ghrelin and appetite, yet whether the response differs in people with or without the rs9939609 A allele is unknown. This study assessed the effect of exercise on appetite, appetite-regulatory hormones and energy intake in variants of the FTO rs9939609 polymorphism.
Cohort
The investigators initially recruited 202 subjects to a database and measured FTO rs9939609 genotype. From these subjects, 12 individuals homozygous for the 'obesity-risk' rs9939609 A allele and 12 homozygous for the T allele were recruited.
A sample size of 24 was chosen based on previous data which suggested that a 34 pg/ml reduction in circulating acylated ghrelin during exercise could be detected with > 80% power with a two-tailed t-test whilst assuming a standard deviation of differences of 54 pg/ml.
Familiarisation trial
First, participants will arrive for a familiarisation trial. Participants will have been fasted for ~2-3 hours beforehand. Participant's height, weight and skinfold measures will be taken. Furthermore, a food preferences questionnaire will be completed to ensure the acceptability of food items provided during the study.
Participants will complete a sub-maximal fitness test, which will last for 16 minutes, and will comprise of four, four minute stages. Initial treadmill speed will be set according to fitness and will be increased every four minutes by 0.5-1.5 km/h. Prior to this test, participants will be fitted with a cannula into an antecubital vein and a blood sample will be withdrawn after the test. This will familiarise participants with the procedure and reduce any stress related to the novelty of the first visit.
Next, a maximal fitness test will be conducted to measure maximal oxygen uptake. This will consist of an incremental protocol where the treadmill gradient will begin at 3.5% and will be increased by 2.5% every 3 minutes. The speed of treadmill will remain constant, and will be determined based on fitness levels. Though the duration of the test is typically 9-15 minutes, it will last until the participant reaches volitional exhaustion.
After the fitness test and adequate recovery time, participants will be presented with a buffet-style meal and instructed to eat until comfortably full and satisfied. To finish, participants will be given a calibrated set of weighing scales and instructions to standardize their food intake before each main trial.
Main trials
Each participant will complete two main trials separated by 7 days: an exercise trial and control trial. In the 24 hours before a main trial, participants will follow a set of standardization procedures. Participants will record all foods consumed and the timings of meals before the first trial. This will be subsequently replicated in the 24 hours prior to the second main trial. Moreover, participants will visit the lab to be provided with a meal and will be instructed to prepare and consume between 19:00-20:00 the night before each main trial. Participants will also be instructed to refrain from strenuous physical activity and alcohol consumption during this period.
Participants will report to the lab on the morning of each trial at 08:00 following an overnight fast. Participants will be instructed to walk slowly to the lab in the morning of each trial.
At 08:30, a cannula will be inserted into an antecubital vein followed by 60 minutes of rest. On the exercise trial, from 09:30 to 10:30, participants will run at a continuous pace that corresponds to 70% of the participant's maximal oxygen uptake. Participants will rest on the bed during this same period of the control trial. Participants will rest and will be provided with a selection of movies to watch for the rest of the trial.
There will be two meals provided to the participants: a standardised meal and an ad libitum buffet style meal. The standardised meal will be a fixed breakfast meal that participants will be provided at 10:50, and will be instructed to consume within 20 minutes. The ad libitum buffet style meal will be given at 15:50 and will consist of an array of foods with differing energy and macronutrient compositions. Participants will be presented with the buffet foods for 30 minutes and will be instructed to eat until comfortably full and satisfied.
Statistical procedures
Linear mixed model, with factors being trial (exercise or control), genotype (AA or TT) and time will be performed on all time-course measures. Area under the curve will be calculated using the trapezoidal rule for outcome measures taken periodically throughout the day. Linear mixed models will also be used for trial and genotype comparisons of area under the curve values and measures not taken throughout the day. At points of interest, where significant main and interaction effects occur, post-hoc analysis was conducted using Holm-Bonferroni adjusted t-tests. Statistical significance was accepted as P < 0.05.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Experimental | Other: ControlExperimental day where participants rest. |
| Exercise | Experimental | Other: ExerciseExperimental day where participants complete a run. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- non-smoker, not currently dieting, weight stable for >3 months (self-reported), no personal history of cardiovascular disease, metabolic disease or dyslipidaemia, European ancestry, no psychiatric or medical condition
Key exclusion criteria (1 listed)
- food allergies, dislike or intolerance of study foods and drinks, irregular eating patterns, use of medication that could influence hormone concentrations
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ControlParticipants complete a resting control condition instead of a run. | Other | Control |
| ExerciseParticipants complete a 60 minute run at 70% of their maximal oxygen uptake | Other | Exercise |
Primary outcome
Plasma acylated ghrelin concentrations (N=24)
Time frame: 24 hours
Measured using ELISA from venous blood samples
Plasma desacyl ghrelin concentrations (N=24)
Time frame: 24 hours
Measured using ELISA from venous blood samples
Subjective appetite (N=24)
Time frame: 24 hours
Measured using visual analogue scales
Ad-libitum energy intake (N=24)
Time frame: 24 hours
Measured at laboratory-based meals
Plasma butyrylcholinesterase activity (N=24)
Time frame: First hour of main trial (three samples).
Measured using Ellman's reagent protocol
3 secondary outcomes
Plasma total glucagon-like peptide 1 concentrations (N=24)
Time frame: 24 hours
Plasma total peptide yy concentrations (N=24)
Time frame: 24 hours
Plasma leptin concentrations (N=24)
Time frame: Baseline (fasting) sample
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2019.
- Background: PubMed 17434869Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. doi: 10.1126/science.1141634. Epub 2007 Apr 12.
- Background: PubMed 18551109Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring). 2008 Aug;16(8):1961-5. doi: 10.1038/oby.2008.318. Epub 2008 Jun 12.
- Background: PubMed 23867619Karra E, O'Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Ruther UU, Bruning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug;123(8):3539-51. doi: 10.1172/JCI44403. Epub 2013 Jul 15.
- Derived from this study: PubMed 31504106Dorling JL, Clayton DJ, Jones J, Carter WG, Thackray AE, King JA, Pucci A, Batterham RL, Stensel DJ. A randomized crossover trial assessing the effects of acute exercise on appetite, circulating ghrelin concentrations, and butyrylcholinesterase activity in normal-weight males with variants of the obesity-linked FTO rs9939609 polymorphism. Am J Clin Nutr. 2019 Nov 1;110(5):1055-1066. doi: 10.1093/ajcn/nqz188.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David J Stensel, PhD principal investigator
Loughborough University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exercise in people with Appetitive Behavior, run by Loughborough University at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma acylated ghrelin concentrations (N=24) (time frame: 24 hours). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03025347, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2019.