High-fat Overfeeding, Hepatokines and Appetite Regulation (OVEREAT)

February 15, 2019 updated by: Scott Willis, Loughborough University

Influence of High-fat Overfeeding on Circulating Hepatokine Concentrations: a Randomised Crossover Study

The present study will investigate the effect of high-fat overfeeding on a group of liver-secreted proteins linked to worsened blood sugar control, as well as proteins involved in appetite control. Participants will consume both a high-fat diet, consisting of 50% extra calories above their daily required intake, and a control diet, consisting of their normal 'habitual' diet, with each diet lasting seven days. The diets will be undertaken in a randomised order, with a period of three weeks separating the two diets. Blood samples will be taken before and after each diet to measure blood sugar control. Further blood samples will also be taken 24 hours and 72 hours into each diet to see how levels of the liver and appetite-regulating proteins change over the course of the seven days.

It is expected that blood sugar control will be worsened by the high-fat diet and this will be accompanied by increases in levels of the liver-secreted proteins and an impaired release of the appetite-regulating proteins into the blood.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

In recent years, researchers have identified a number of liver-secreted proteins, termed "hepatokines", which are thought to play an important role in inter-organ crosstalk between the liver and other metabolically active tissues such as skeletal muscle and adipose tissue. Specifically, previous studies have demonstrated that hepatokines contribute to whole body glucose and lipid homeostasis through acting in an endocrine-like fashion. Understanding how circulating concentrations of these hepatokines can be manipulated in humans is essential, as impaired blood glucose and lipid control is a key feature of metabolic diseases, such as type 2 diabetes and non-alcoholic fatty liver disease.

Previous research at Loughborough University has found that acute high-fat overfeeding for up to seven days can impair glycaemic control; however, the exact mechanisms responsible for these detrimental changes are not fully understood. Based upon previous evidence that hepatokine production is nutritionally modulated, the investigators believe that changes in hepatokine production may play a role in the detrimental metabolic effects seen following short-term, high-fat overfeeding which has implications for long-term metabolic health.

Appetite regulation is also thought to play a role in the pathophysiology of obesity and insulin resistance, as the impaired secretion of several appetite regulatory hormones in both fasting and postprandial conditions has been observed in obesity, which is characterised by an chronic excessive energy intake. Therefore, the investigators are also interested to examine the appetite regulatory hormone response to short-term, high-fat overfeeding.

The present study is a randomised, controlled, crossover study in which twelve recreationally active, healthy males will consume both a hypercaloric, high-fat diet (consisting of 50% extra energy above the daily requirement, 65% of which is fat) and a control diet (the participants' habitual diet) in a randomised fashion. A three-week washout period will separate the two diets in order to remove any lasting effects confounding the subsequent diet.

Following a prescreening session in which anthropometric data will be collected, participants will commence their first dietary condition. An oral glucose tolerance test will be performed before and after the two diets to measure changes in glycaemic control/whole body insulin sensitivity. Further blood samples will be taken 24 hours and 72 hours after commencing the diets in order to observe the time course of any changes in circulating hepatokine and appetite hormone concentrations. Physical activity will also be monitored for the duration of the two dietary conditions to ensure that habitual physical activity levels are maintained.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Leicestershire
      • Loughborough, Leicestershire, United Kingdom, LE11 3TU
        • National Centre for Sport and Exercise Medicine, Loughborough University
    • Nottinghamshire
      • Nottingham, Nottinghamshire, United Kingdom, NG1 4FQ
        • Clifton Campus, Nottingham Trent University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 36 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Recreationally active - ≤ 2 structured exercise sessions per week
  • BMI between 18.5 - 27.9 kg/m2
  • Body fat percentage < 20%
  • Metabolically healthy - No known cardiovascular or metabolic disease such as diabetes, respiratory or heart disease.
  • Non-smoker
  • Weight stable in the past 6 months
  • Normal fasting blood glucose levels (3.6 - 5.5 mmol/l)

Exclusion Criteria:

  • Contraindications to exercise
  • Needle Phobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: High-fat diet
Participants will consume a hypercaloric, high-fat diet. Participants will be provided with all the food during the week and will be instructed to consume all of the foods provided and no extra calorie containing food or drink. In the event of leftover food, participants will be asked to return the food for measurement and subsequent subtraction from their total energy intake.
Dietary supplement: High-fat diet
The high-fat diet will provide 7 days of overfeeding comprising of: +50% extra calories above the daily required intake, 65% of which is fat.
No Intervention: Control diet
Participants will consume their normal 'habitual' diet for seven days which will be compared to their habitual diet recorded by a three day food diary before commencing the two diets. Participants will be instructed to carry on as normal and eat their usual diet and this period will be used as a comparator to the high-fat diet. They will also be told to record their food intake for 3 days during the diet to quantify their control diet.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Leukocyte cell-derived chemotaxin 2 (LECT2)
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of LECT2 plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Fibroblast growth factor 21 (FGF21)
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of FGF21 plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
Fetuin-A
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of Fetuin-A plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
Acylated ghrelin
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of acylated ghrelin plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
Peptide YY (PYY)
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of PYY plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
C-Terminal Telopeptide of Type 1 Collagen (CTX)
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of CTX plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
N-Terminal Propeptide of Type 1 Procollagen (P1NP)
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of P1NP plasma concentrations across the 7-day dietary interventions
Baseline, 1 day, 3 days, 7 days
Visual Analogue Scale for Subjective Ratings of Appetite
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of subjective ratings of hunger across the 7-day dietary interventions, measured using an appetite visual analogue scale. The scale is divided into subscales of different appetite perceptions including: hunger, fullness, satisfaction and prospective food consumption. Each subscale is rated on a 100mm scale (i.e. from 0 - 100), with a rating of 100 fully supporting the perception and a rating of 0 fully opposing the perception.
Baseline, 1 day, 3 days, 7 days
Subjective food preference
Time Frame: Baseline, 1 day, 3 days, 7 days
Time-course of subjective food preference across the 7-day dietary interventions, measured using the Leeds Food Preference Questionnaire.
Baseline, 1 day, 3 days, 7 days
Whole-body insulin sensitivity
Time Frame: Baseline, 7 Days
Changes in whole-body insulin sensitivity using the Matsuda Index, calculated from plasma glucose and insulin concentrations during the oral glucose tolerance test
Baseline, 7 Days
Homeostasis model assessment of insulin resistance (HOMA-IR)
Time Frame: Baseline, 1 day, 3 days, 7 days
Changes in HOMA-IR (a marker of hepatic insulin resistance) using baseline concentrations of plasma glucose and insulin.
Baseline, 1 day, 3 days, 7 days
Adipose tissue insulin resistance (ADIPO-IR)
Time Frame: Baseline, 1 day, 3 days, 7 days
Changes in ADIPO-IR using baseline concentrations of plasma insulin and non-esterified free fatty acids.
Baseline, 1 day, 3 days, 7 days
Physical activity and sedentary behaviour
Time Frame: 7 days (per diet)
Amounts of sitting time, standing time, light activity and moderate-vigorous activity will be measured across the duration of each diets to compare between the two. This will be Measured using Acitgraph and ActivPAL monitors.
7 days (per diet)
Resting Metabolic Rate
Time Frame: Baseline, 7 Days
Changes in resting metabolic rate in response to the diets will be measured using indirect calorimetry and estimated using the Haldane transformation.
Baseline, 7 Days
Fat Oxidation
Time Frame: Baseline, 7 Days
Changes in fat oxidation in response to the diets will be measured using indirect calorimetry and estimated using the Haldane transformation.
Baseline, 7 Days
Blood pressure
Time Frame: Baseline, 1 day, 3 days, 7 days
Changes in blood pressure (systolic and diastolic) across the two dietary interventions will be measured using an automated pressure cuff.
Baseline, 1 day, 3 days, 7 days
Body weight
Time Frame: Baseline, 1 day, 3 days, 7 days
Changes in body weight across the two dietary interventions.
Baseline, 1 day, 3 days, 7 days
Body fat percentage
Time Frame: Baseline, 7 Days
Changes in body fat percentage across the two dietary interventions using bioelectrical impedance analysis.
Baseline, 7 Days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Loughborough University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Nottingham University Hospitals NHS Trust
Nottingham Trent University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James A King, PhD, Loughborough University
  • Principal Investigator: Scott A Willis, MSc, Loughborough University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 31, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 31, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 18, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 15, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • R17-P144

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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