FastingNCT03757767
The Fasting Study - Unraveling the Mechanistic Effects of Prolonged Fasting in Humans.
A study testing Fasting for 26-hours in people with Fasting and Adipose Tissue, run by Wageningen University at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 40 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Fasting, Adipose Tissue, Clinical Trial
- What is being tested?
- Fasting for 26-hours
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 12 Nov 2018to 22 Jan 2019
- 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 40 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Willing to consume the standardized meal on test day 1
- Signed informed consent
- Having a general practitioner
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Wageningen University, Division of Human Nutrition
Wageningen, Gelderland, 6700 EV
About this study
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.
Read the 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.
- Conditions
- Fasting, Adipose Tissue, Clinical Trial, Lipid Metabolism
- Being tested
- Fasting for 26-hours
- Keywords
- Physiology, Humans
- Medical subject headings
- Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fasting for 26-hoursOther
Also called Prolonged fasting
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention arm | Experimental | Fasting for 26-hours. Receives: Other: Fasting for 26-hours |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in ANGPTL4 protein and gene expression in adipose tissue
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.
Measured: 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
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.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Change in ANGPTL4 expression in plasma
Using ELISA, the change in ANGPTL4 expression in plasma will be measured from fed to a prolonged fasted state.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Change in ANGPTL4 and LPL gene expression in PBMCs
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.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Secondary outcomes (4)
Change in whole genome expression
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.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Post-transcriptional changes
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.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Changes in metabolite profiles
Using untargeted and targeted metabolomic platforms, the changes in metabolite profiles in the adipose tissue and plasma/serum will be measured.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Changes in protein profiles
Using untargeted and targeted proteomic platforms, the changes in protein profiles in the adipose tissue and plasma/serum will be measured.
Measured: There are 24 hours between the measurement in the fed and the fasted state
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2018
- Study start12 Nov 2018
- Primary completion22 Jan 2019
- Study completion22 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FastingStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- Research subjects are measured in the fed state and in the prolonged fasted state.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wageningen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Lydia A. Afman, Wageningen University
- Investigators
- Lydia Afman, PhD, Principal investigator, Wageningen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03757767
- Sponsor's protocol ID
- NL-66589.081.18
- Status last verified
- Apr 2019
- First submitted
- 9 Nov 2018
- Last updated
- 24 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Collected data will be coded.
Publications
Ruppert PMM, Michielsen CCJR, Hazebroek EJ, Pirayesh A, Olivecrona G, Afman LA, Kersten S. Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue. Mol Metab. 2020 Oct;40:101033. doi: 10.1016/j.molmet.2020.101033. Epub 2020 Jun 3.
PubMed 32504883
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Fasting Study - Unraveling the Mechanistic Effects of Prolonged Fasting in Humans.
- ClinicalTrials.gov ID
- NCT03757767
- Acronym / sponsor ID
- NL-66589.081.18
- Conditions
- Fasting, Adipose Tissue, Clinical Trial, Lipid Metabolism
- Keywords
- Physiology, Humans
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Wageningen UniversityUniversity, hospital or other
- Study start
- 12 Nov 2018 (actual)
- Primary completion
- 22 Jan 2019 (actual)
- Study completion
- 22 Jan 2019 (actual)
- First posted
- 29 Nov 2018 (actual)
- 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.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Research subjects are measured in the fed state and in the prolonged fasted state.
| Arm | Type | Receives |
|---|---|---|
| Intervention arm | Experimental | Other: Fasting for 26-hoursFasting for 26-hours. |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| Fasting for 26-hoursAlso: Prolonged fastingAll 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 | Intervention arm |
Primary outcome
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.
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.
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.
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.
4 secondary outcomes
Change in whole genome expression
Time frame: 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
Changes in metabolite profiles
Time frame: 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
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 24 Apr 2019.
- Derived from this study: PubMed 32504883Ruppert PMM, Michielsen CCJR, Hazebroek EJ, Pirayesh A, Olivecrona G, Afman LA, Kersten S. Fasting induces ANGPTL4 and reduces LPL activity in human adipose tissue. Mol Metab. 2020 Oct;40:101033. doi: 10.1016/j.molmet.2020.101033. Epub 2020 Jun 3.
- Individual participant dataSharing planned: Undecided. Collected data will be coded.
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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.
Lydia Afman, PhD principal investigator
Wageningen 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 Fasting for 26-hours in people with Fasting and Adipose Tissue, run by Wageningen University at 1 site in Netherlands.
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 9 inclusion and 14 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 24 Apr 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 Netherlands. 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?
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). The study lists 4 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 NCT03757767, which also lists 1 linked publication.
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 24 Apr 2019.