AsthmaNCT02719899
Effect of Fasting and Refeeding on T-cell Fate
An observational study of Asthma and Inflammation, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Researchers want to better understand the body s immune response to calorie restriction. To do this, they are asking healthy volunteers to fast for 24 hours. Researchers will test immune response before and after fasting. Objectives: To explore the benefits of calorie restriction on immune health. Read more about this study
- Who is it for?
- Ages 21 to 37 years
- Conditions the study is for
- Asthma, Inflammation
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2016to 24 Feb 2017
- Phase
- Observational
- 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 21 to 37 years
- All sexes
- No healthy volunteers
- Adult
Study population: -Males and females between the ages of 21 and 37 @@@-BMI greater than or equal to 22 and less than 30
Who may be able to join
- As this is a pilot study, the age-range and BMI range of subjects will be restricted to potentially reduce metabolic variables associated with a wide age- and BMI-range.
- Males and females between the ages of 21 and 37
- BMI greater than or equal to 22 and less than 30
Who cannot join
- Subjects with an acute or chronic illness as per history, on laboratory analysis or due to use of medications
- Subjects taking vitamins or supplements or any medications, except oral contraceptives, within 4 weeks of participation into this study
- BMI less than 22 or greater than or equal to 30
- Female subjects who are pregnant or lactating
- Subjects who have donated blood or participated in another clinical trial involving blood draws in the last 8 weeks
- Subjects who use nicotine products
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study to Evaluate the Effect of Fasting and Refeeding on T-Cell Fate
Background:
Researchers want to better understand the body s immune response to calorie restriction. To do this, they are asking healthy volunteers to fast for 24 hours. Researchers will test immune response before and after fasting.
Read more
Objectives:
To explore the benefits of calorie restriction on immune health.
Eligibility:
Healthy volunteers ages 21 to 37 with a body mass index between 22 and 29.
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Participants will visit NIH after an overnight fast. Their baseline immune response will be taken. They will give blood and urine samples. Then they will be given breakfast. This visit will take about 2 hours.
Participants will fast (not eat or drink anything except water) for the next 24 hours. They will return to NIH the next morning. Their immune response will be taken. They will give blood and urine samples. Then they will be given breakfast. Their immune response will be taken 3 hours later. They will give a blood sample. This visit will take about 4 hours.
Read the detailed description
Intermittent caloric restricted or fasting has numerous health effects including the reduction in numerous cardiovascular and pulmonary disease risk factors. The cellular programs activated by caloric restriction are similarly regulated in preclinical and clinical studies in response to a 24-hour fast. We have found that a beneficial effect of a 24-hour fasting blunts the activation of a component of the innate immune system, termed the NLRP3 inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with the development of diabetes, asthma and atherosclerosis. At the same time, we found that refeeding after the 24-hour fast significantly increased NLRP3 protein levels. As NLRP3 is increased in obesity, the nutrient intervention (24 hour fast and then refeeding) we studied may be useful to evaluate nutrient-overload effects on the immune system. Pertaining to this it has recently been found in a preclinical study that NLRP3 can also orchestrate differentiation of na(SqrRoot) ve T cells into T(H)2 cells. Interestingly both the NLRP3 inflammasome and T(H)2 cell activation contribute to asthma. In this context we hypothesize that the assessment of the effect on refeeding on T(H)2 cell differentiation (polarity) may allow us to dissect out the mechanisms underpinning nutrient overload induced T(H)2 cell activation. To evaluate this blood samples to test T-cell biology will be collected in subjects, at baseline, after a fixed caloric meal and in response to a 24-hour fast (water intake will not be restricted). The objective of this pilot study is to identify if nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases including asthma.
- Conditions
- Asthma, Inflammation
- Keywords
- NLRP3 Inflammasome, Sirtuin 3, T-Cell Polarity, Caloric Restriction, Natural History
- Medical subject headings
- Asthma, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Healthy Volunteers |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be the change in TH2 cell cytokine (IL-4, IL-5 and/or IL-13) secretion in response to T-cell differentiation comparing the fasted to the refeeding response.
The comparisons will be performed using paired two-tailed Student t-tests. Significance will be tested at the 0.05 alpha level in this pilot study
Measured: 24 hours
Secondary outcomes (2)
To identify if nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway could be investigated as atherapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases includin...
Blood samples to test T-cell biology will be collected in subjects, at baseline, after a fixed caloric meal and in response to a 24-hour fast (water intake will not be restricted). Analysis of T-cell interleukin expression and regulation and mitochondrial functioning in primary T-cells. Analysis of mitochondrial biology in these immune-modulatory effects.
Measured: Visit 3, 3hrs post-meal
Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs.
Analysis of difference in additional T-cell polarity signatures. Analysis ofcytokine and other protein levels in serum comparing the fed versus fasted states. Analysis of serum metabolites that may be modulating T-cell polarity.
Measured: Visit 3, 3hrs post-meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2016 (estimated)
- Study start18 Apr 2016
- Primary completion24 Feb 2017
- Study completion24 Feb 2017
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 AsthmaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Michael N Sack, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02719899
- Sponsor's protocol ID
- 160085
- Other IDs
- 16-H-0085
- Status last verified
- Jun 2025
- First submitted
- 24 Mar 2016
- Last updated
- 29 Jun 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sack MN, Finkel T. Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a013102. doi: 10.1101/cshperspect.a013102.
PubMed 23209156Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. doi: 10.1073/pnas.0308291101. Epub 2004 Apr 19.
PubMed 15096581Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015 Mar 26;161(1):106-118. doi: 10.1016/j.cell.2015.02.020.
PubMed 25815989Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, Huffstutler RD, Seifuddin F, Dagur PK, Saxena A, McCoy JP, Chen J, Biancotto A, Stagliano KER, Teague HL, Mehta NN, Pirooznia M, Sack MN. Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness. Nat Metab. 2021 Mar;3(3):318-326. doi: 10.1038/s42255-021-00356-0. Epub 2021 Mar 15.
PubMed 33723462
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate the Effect of Fasting and Refeeding on T-Cell Fate
- ClinicalTrials.gov ID
- NCT02719899
- Acronym / sponsor ID
- 160085
- Conditions
- Asthma, Inflammation
- Keywords
- NLRP3 Inflammasome, Sirtuin 3, T-Cell Polarity, Caloric Restriction, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 18 Apr 2016 (actual)
- Primary completion
- 24 Feb 2017 (actual)
- Study completion
- 24 Feb 2017 (actual)
- First posted
- 25 Mar 2016 (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.
Background:
Researchers want to better understand the body s immune response to calorie restriction. To do this, they are asking healthy volunteers to fast for 24 hours. Researchers will test immune response before and after fasting.
Objectives:
To explore the benefits of calorie restriction on immune health.
Eligibility:
Healthy volunteers ages 21 to 37 with a body mass index between 22 and 29.
Design:
Participants will be screened with medical history, physical exam, and blood tests.
Participants will visit NIH after an overnight fast. Their baseline immune response will be taken. They will give blood and urine samples. Then they will be given breakfast. This visit will take about 2 hours.
Participants will fast (not eat or drink anything except water) for the next 24 hours. They will return to NIH the next morning. Their immune response will be taken. They will give blood and urine samples. Then they will be given breakfast. Their immune response will be taken 3 hours later. They will give a blood sample. This visit will take about 4 hours.
Detailed description
Intermittent caloric restricted or fasting has numerous health effects including the reduction in numerous cardiovascular and pulmonary disease risk factors. The cellular programs activated by caloric restriction are similarly regulated in preclinical and clinical studies in response to a 24-hour fast. We have found that a beneficial effect of a 24-hour fasting blunts the activation of a component of the innate immune system, termed the NLRP3 inflammasome. This inflammasome, as a mediator of sterile inflammation, is associated with the development of diabetes, asthma and atherosclerosis. At the same time, we found that refeeding after the 24-hour fast significantly increased NLRP3 protein levels. As NLRP3 is increased in obesity, the nutrient intervention (24 hour fast and then refeeding) we studied may be useful to evaluate nutrient-overload effects on the immune system. Pertaining to this it has recently been found in a preclinical study that NLRP3 can also orchestrate differentiation of na(SqrRoot) ve T cells into T(H)2 cells. Interestingly both the NLRP3 inflammasome and T(H)2 cell activation contribute to asthma. In this context we hypothesize that the assessment of the effect on refeeding on T(H)2 cell differentiation (polarity) may allow us to dissect out the mechanisms underpinning nutrient overload induced T(H)2 cell activation. To evaluate this blood samples to test T-cell biology will be collected in subjects, at baseline, after a fixed caloric meal and in response to a 24-hour fast (water intake will not be restricted). The objective of this pilot study is to identify if nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases including asthma.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Healthy Volunteers |
Who may qualify
- Ages
- 21 to 37 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- -Males and females between the ages of 21 and 37 @@@-BMI greater than or equal to 22 and less than 30
Key inclusion criteria (3 listed)
- As this is a pilot study, the age-range and BMI range of subjects will be restricted to potentially reduce metabolic variables associated with a wide age- and BMI-range.
- Males and females between the ages of 21 and 37
- BMI greater than or equal to 22 and less than 30
Key exclusion criteria (6 listed)
- Subjects with an acute or chronic illness as per history, on laboratory analysis or due to use of medications
- Subjects taking vitamins or supplements or any medications, except oral contraceptives, within 4 weeks of participation into this study
- BMI less than 22 or greater than or equal to 30
- Female subjects who are pregnant or lactating
- Subjects who have donated blood or participated in another clinical trial involving blood draws in the last 8 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The primary outcome will be the change in TH2 cell cytokine (IL-4, IL-5 and/or IL-13) secretion in response to T-cell differentiation comparing the fasted to the refeeding response.
Time frame: 24 hours
The comparisons will be performed using paired two-tailed Student t-tests. Significance will be tested at the 0.05 alpha level in this pilot study
2 secondary outcomes
To identify if nutrient-load regulates T-Cell differentiation capacity and to test whether this pathway could be investigated as atherapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases includin...
Time frame: Visit 3, 3hrs post-meal
Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs.
Time frame: Visit 3, 3hrs post-meal
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 29 Jun 2025.
- Background: PubMed 23209156Sack MN, Finkel T. Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harb Perspect Biol. 2012 Dec 1;4(12):a013102. doi: 10.1101/cshperspect.a013102.
- Background: PubMed 15096581Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6659-63. doi: 10.1073/pnas.0308291101. Epub 2004 Apr 19.
- Background: PubMed 25815989Fontana L, Partridge L. Promoting health and longevity through diet: from model organisms to humans. Cell. 2015 Mar 26;161(1):106-118. doi: 10.1016/j.cell.2015.02.020.
- Derived from this study: PubMed 33723462Han K, Singh K, Rodman MJ, Hassanzadeh S, Wu K, Nguyen A, Huffstutler RD, Seifuddin F, Dagur PK, Saxena A, McCoy JP, Chen J, Biancotto A, Stagliano KER, Teague HL, Mehta NN, Pirooznia M, Sack MN. Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness. Nat Metab. 2021 Mar;3(3):318-326. doi: 10.1038/s42255-021-00356-0. Epub 2021 Mar 15.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Michael N Sack, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and Inflammation, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
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 3 inclusion and 6 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 29 Jun 2025. 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 States. 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?
The primary outcome will be the change in TH2 cell cytokine (IL-4, IL-5 and/or IL-13) secretion in response to T-cell differentiation comparing the fasted to the refeeding response. (time frame: 24 hours). 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 NCT02719899, 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 29 Jun 2025.