The Fasting Study - Unraveling the Mechanistic Effects of Prolonged Fasting in Humans.

April 23, 2019 updated by: Lydia A. Afman, Wageningen University
Elevated levels of plasma triglycerides are increasingly recognized as an important causal risk factor for cardiovascular disease and associated pathologies. Lowering plasma triglycerides may therefore be a therapeutic target to lower cardiovascular disease risk. With this study the investigators want to examine the effects of fasting on adipose tissue metabolism in humans.

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

Rationale: Elevated levels of plasma triglycerides are increasingly recognized as an important causal risk factor for cardiovascular disease and associated pathologies. Lowering plasma triglycerides may therefore be a therapeutic target to lower cardiovascular disease risk. Lipoprotein lipase (LPL) is the enzyme that catalyzes the hydrolysis of plasma triglycerides into fatty acids on the capillary endothelium, thereby lowering plasma triglycerides and stimulating the uptake of these fatty acids into cells. Angiopoietin-like 4 (ANGPTL4) is produced by fat cells and promotes the unfolding and inactivation of LPL, leading to decreased hydrolysis of plasma triglycerides. The role of ANGPTL4 in regulating LPL is especially important during fasting. However, as most studies are performed in animal models, little is known about the effects of fasting on adipose tissue metabolism in humans, and specifically on ANGPTL4 and its relationship with LPL.

Objectives: The key objective of this study is to determine the effect of a prolonged fast on ANGPTL4 gene and protein expression in subcutaneous adipose tissue, the key organ involved in lipid metabolism. Additionally, the effect of a prolonged fast on LPL gene expression, LPL protein expression, and on LPL activity in subcutaneous adipose tissue will be examined. To explore the systemic effects of a prolonged fast, the investigators will also measure ANGPTL4 levels in plasma, and ANGPTL4 and LPL gene expression in circulating immune cells (PBMCs). The secondary objective of this study is to obtain a more holistic view on the changes occurring upon a prolonged fast, by examining the effects of fasting on whole genome expression, post-transcriptional changes, and on markers of metabolic status. The combined results of all measurements will ultimately lead to a better understanding of the mechanistic effects of a prolonged fast and the metabolic functioning in humans.

Study design: The Fasting Study is a single arm intervention study in healthy men and women. The investigators will examine the effects of a fed state, which is 2 hours after the last food intake, versus a prolonged fasted state, which is 26 hours after the last food intake. Adipose tissue biopsies and blood samples will be taken 2 hours after the last meal and 26 hours after the last meal. The 24 hours between sampling points are chosen to prevent effects of the circadian rhythm.

Study population: The study population will consist of 24, 40-70 years old men and women with a BMI of 22-30 kg/m2, selected from the surroundings of Wageningen through the mailing list for potential study research subjects of the division of Human Nutrition and health of Wageningen University. If needed, additional recruitment of research subjects will take place by flyers and posters, or advertisements in local newspapers.

Intervention: All research subjects will start with the consumption of a standardized meal (ad libitum). Directly thereafter the intervention begins, which is a fasting period of twenty-six-hours, during which research subjects are not allowed to eat or drink anything except for water, which the research subjects may consume ad libitum. The investigators will take the first blood samples and adipose tissue biopsies two hours after the consumption of the standardized meal. This is the fed state: the point in time where the body is physiologically fed, based on the average time for plasma free fatty acids to drop. Twenty-four hours after the "fed state", research subjects are in the prolonged fasted state, and the investigators will take the final blood samples and adipose tissue biopsies. The time period of twenty-four-hours between sampling points is chosen to prevent the effects of circadian related changes on our outcome measures.

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.
24

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

  • Netherlands
    • Gelderland
      • Wageningen, Gelderland, Netherlands, 6700 EV
        • Wageningen University, Division of Human Nutrition

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

40 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Apparently healthy man or woman
  • Age 40-70y at the time of recruitment
  • BMI of 22-30 kg/m2
  • Willing to fast for 26 hours
  • Willing to give blood samples
  • Willing to give adipose tissue biopsies
  • Willing to consume the standardized meal on test day 1
  • Signed informed consent
  • Having a general practitioner

Exclusion Criteria:

  • Alcohol on average: more than 2 consumptions/day or more than 14 consumptions/week
  • Tobacco smoker
  • Usage of drugs
  • Following a diet within one month of starting the study (for example a ketogenic diet)
  • Allergic to one or more components of the standardized meal
  • Donated or intend to donate blood from 2 months before the study until the end of the study
  • Unstable body weight (weight gain or loss >5 kg in the past three months)
  • Diagnosed with any long-term medical condition that can interfere with the study outcome (i.e. cardiovascular disease, diabetes mellitus type 1 or 2, liver, pulmonary, or renal disease)
  • Use of prescribed medication
  • Use of supplements or over the counter medication (OTC) known to interfere with glucose or lipid homeostasis in the week before the start of the study, and during the study
  • Being pregnant or lactating
  • Participation in another biomedical study (other than the EetMeetWeet study) during this study
  • Members of the research team, or first degree family members of the research team
  • Working, or doing an internship at the division "Human Nutrition and Health" - Wageningen University

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: N/A
  • Interventional Model: Single Group 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: Intervention arm
Fasting for 26-hours.
Other: Fasting for 26-hours

All research subjects will have to fast for 26 hours in total.

All research subjects start with a standardized meal. Two hours after the standardized meal the samples in the fed state will be taken. Research participants are not allowed to eat anything after the consumption of the standardized meal until the second measurements on day 2, 26-hours later. There are 24 hours between the two measurement points.

Other Names:
  • Prolonged fasting

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
Change in ANGPTL4 protein and gene expression in adipose tissue
Time Frame: there are 24 hours between the measurement in de fed and the fasted state
Using Western blotting, the change in ANGPTL4 protein expression in adipose tissue will be measured from fed to a prolonged fasted state. The change in ANGPTL4 gene expression in adipose tissue will be measured from fed to a prolonged fasted state using whole genome affymetrix microarrays and targeted quantitative real time PCR.
there are 24 hours between the measurement in de fed and the fasted state
Change in LPL expression, both gene and protein, and LPL activity in adipose tissue
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using Western blotting, the change in LPL protein expression in adipose tissue will be measured from fed to a prolonged fasted state. The change in LPL gene expression in adipose tissue will be measured from fed to a prolonged fasted state using whole genome affymetrix microarrays and targeted quantitative real time PCR. The change in LPL activity in subcutaneous adipose tissue will be measured from fed to a prolonged fasted state, using a lipoprotein lipase assay.
There are 24 hours between the measurement in the fed and the fasted state
Change in ANGPTL4 expression in plasma
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using ELISA, the change in ANGPTL4 expression in plasma will be measured from fed to a prolonged fasted state.
There are 24 hours between the measurement in the fed and the fasted state
Change in ANGPTL4 and LPL gene expression in PBMCs
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
The change in ANGPTL4 and LPL gene expression in PBMCs from fed to a prolonged fasted state will be measured using whole genome affymetrix microarrays and targeted quantitative real time PCR.
There are 24 hours between the measurement in the fed and the fasted state

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
Change in whole genome expression
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using whole genome affymetrix micorarrays, the change in whole genome gene expression in both adipose tissue and PBMCs will be measured from fed to a prolonged fasted state.
There are 24 hours between the measurement in the fed and the fasted state
Post-transcriptional changes
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using microRNAarrays of Thermo Fisher Scientific, targeted digital droplet PCR, and quantitative real time PCR, post-transcriptional changes in adipose tissue and PBMCs will be measured from fed to a prolonged fasted state.
There are 24 hours between the measurement in the fed and the fasted state
Changes in metabolite profiles
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using untargeted and targeted metabolomic platforms, the changes in metabolite profiles in the adipose tissue and plasma/serum will be measured.
There are 24 hours between the measurement in the fed and the fasted state
Changes in protein profiles
Time Frame: There are 24 hours between the measurement in the fed and the fasted state
Using untargeted and targeted proteomic platforms, the changes in protein profiles in the adipose tissue and plasma/serum will be measured.
There are 24 hours between the measurement in the fed and the fasted state

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
BMI
Time Frame: At baseline
weight (in kg) and height (in meters) will be measured and combined to report BMI in kg/m^2
At baseline

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.
Wageningen 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: Lydia Afman, PhD, Wageningen 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.
November 12, 2018

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.
January 22, 2019

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.
January 22, 2019

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 9, 2018

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.
November 26, 2018

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.
November 29, 2018

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.
April 24, 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.
April 23, 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.
April 1, 2019

More Information

Terms related to this study

Keywords

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.
  • NL-66589.081.18

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Collected data will be coded.

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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