AsthmaNCT02471300
Effect of Fasting on the Asthma Inflammasome
An observational study of Asthma, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Research shows that restricting calories has a positive effect on immune cell health in healthy people. Researchers want to learn if it will help people with asthma. They want to better understand how the body s immune response and lung function responds to short-term calorie restriction. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Asthma
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2015to 27 Jan 2021
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Study population: -Males and females between the ages of 18 and 60@@@-Asthmatic subjects will have a history consistent with asthma, be on chronic asthma therapy and have prior documentation of reversible airflow obstruction based upon either a positive response to an inhaled bronchodilator or a positive methacholine broncho-provocation challenge test@@@@@@
Who may be able to join
- Males and females between the ages of 18 and 60
- Asthmatic subjects will have a history consistent with asthma, be on chronic asthma therapy and have prior documentation of reversible airflow obstruction based upon either a positive response to an inhaled bronchodilator or a positive methacholine bronchoprovocation challenge test
Who cannot join
- Subjects with concurrent acute illness or other chronic illnesses associated with inflammation including diabetes requiring medical management.
- 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.
- Medical condition identified by screening bloodwork that would preclude safe participation or valid data collection.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study to Evaluate the Effect of Fasting on the Asthma Inflammasome
Background:
Research shows that restricting calories has a positive effect on immune cell health in healthy people. Researchers want to learn if it will help people with asthma. They want to better understand how the body s immune response and lung function responds to short-term calorie restriction. For this, they want people to fast (no food or drink except water) for 24 hours.
Read more
Objective:
To explore the benefits of calorie restriction in people with asthma.
Eligibility:
Healthy people ages 18 to 60 who have a history consistent with asthma and prior documentation of airflow obstruction or wheezing.
Design:
- Participants who have taken part in asthma research at NIH will be screened with a telephone interview. All other participants will have a medical history, blood tests, and physical exam.
- Eligible participants will return to the NIH Clinical Center one morning for 2 hours. They will be fed breakfast. They may have blood and urine tests.
- Participants will then fast for 24 hours.
- Participants will return to the Clinical Center the next morning for 4 hours. They will have blood drawn. They will eat breakfast and then repeat blood draws 2.5 hours later. They will have a urine test.
- Blood and urine tests will be done at the end of the fast and after the meals to confirm that the participant fasted for the full 24-hour period.
- Participants will have lung function tests and exhaled gas measurements. A machine will measure the volume of air they can breathe out. Some gases in the breath increase with inflammation. Participants will breathe into a machine that analyzes the gases in their breath.
Read the detailed description
The NLRP3 inflammasome is part of the innate immune system that can be activated by atherosclerosis, gout and diabetes (sterile inflammation). As mitochondrial signaling can trigger the NLRP3 inflammasome, we initially proposed that fasting, via a nutrient-sensing mitochondrial program, would dampen this innate immune program. Our preliminary data shows that a 24-hour fasting does blunt NLRP3 inflammasome activation in healthy young individuals. Interestingly, this inflammasome program has been implicated in the pathophysiology of bronchoreactivity linked to asthma and intermittent fasting has been found to reduce disease exacerbations in asthmatic patients. The objective of this protocol will extend our investigations, from what we are finding in young control normal volunteers, to enable us to investigate stable mild-moderate asthmatic subjects to determine whether fasting can blunt inflammasome activation and assess whether this transient nutrient-deprivation maneuver can improve airflow. Blood samples and pulmonary function testing to assay the immune response and bronchoreactivity will be performed in subjects in response to a 24-hour fast (water intake will not be restricted) followed by re-testing 3 hours after a fixed caloric meal. The objective of this pilot study is to identify if these immune adaptive pathways can be subdued in human subjects with a known inflammasome linked disease. Additionally, this study may enable us to identify a potential therapeutic pathway to blunt/negate inflammation associated with nutrient-excess associated bronchoreactivity of asthma.
- Conditions
- Asthma
- Keywords
- Asthma, Inflammasome, Fasting, Airflow Obstruction
- Medical subject headings
- Asthma, Fasting
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 | stable mild-moderate asthmatic subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in IL-1-beta secretion in response to inflammasome stimulation in PBMCs comparing the fasted response to the fed response
Determine whether the NLRP3 inflammasome is blunted by a 24-hour fast in PBMC s in subjects with mild to moderate asthma.Initiate 24-hour fast with the exception of drinking water and use of asthma medications until midnight. Patients will be asked to hold their asthma medications after midnight. Fasting research labs to study the inflammasome and Fed State Research Labs to study the inflammasome.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study start26 Aug 2015
- Primary completion6 Mar 2017
- Study completion27 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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
- Case only
- Time perspective
- Prospective
- Enrolment
- 19 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
- NCT02471300
- Sponsor's protocol ID
- 150136
- Other IDs
- 15-H-0136
- Status last verified
- Jan 2021
- First submitted
- 12 Jun 2015
- Last updated
- 1 Feb 2021
- Results posted
- No
Publications
Besnard AG, Guillou N, Tschopp J, Erard F, Couillin I, Iwakura Y, Quesniaux V, Ryffel B, Togbe D. NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy. 2011 Aug;66(8):1047-57. doi: 10.1111/j.1398-9995.2011.02586.x. Epub 2011 Mar 28.
PubMed 21443539Kim SR, Kim DI, Kim SH, Lee H, Lee KS, Cho SH, Lee YC. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation. Cell Death Dis. 2014 Oct 30;5(10):e1498. doi: 10.1038/cddis.2014.460.
PubMed 25356867Kim HY, Lee HJ, Chang YJ, Pichavant M, Shore SA, Fitzgerald KA, Iwakura Y, Israel E, Bolger K, Faul J, DeKruyff RH, Umetsu DT. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med. 2014 Jan;20(1):54-61. doi: 10.1038/nm.3423. Epub 2013 Dec 15.
PubMed 24336249
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study to Evaluate the Effect of Fasting on the Asthma Inflammasome
- ClinicalTrials.gov ID
- NCT02471300
- Acronym / sponsor ID
- 150136
- Conditions
- Asthma
- Keywords
- Asthma, Inflammasome, Fasting, Airflow Obstruction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 26 Aug 2015 (actual)
- Primary completion
- 6 Mar 2017 (actual)
- Study completion
- 27 Jan 2021 (actual)
- First posted
- 15 Jun 2015 (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:
Research shows that restricting calories has a positive effect on immune cell health in healthy people. Researchers want to learn if it will help people with asthma. They want to better understand how the body s immune response and lung function responds to short-term calorie restriction. For this, they want people to fast (no food or drink except water) for 24 hours.
Objective:
To explore the benefits of calorie restriction in people with asthma.
Eligibility:
Healthy people ages 18 to 60 who have a history consistent with asthma and prior documentation of airflow obstruction or wheezing.
Design:
- Participants who have taken part in asthma research at NIH will be screened with a telephone interview. All other participants will have a medical history, blood tests, and physical exam.
- Eligible participants will return to the NIH Clinical Center one morning for 2 hours. They will be fed breakfast. They may have blood and urine tests.
- Participants will then fast for 24 hours.
- Participants will return to the Clinical Center the next morning for 4 hours. They will have blood drawn. They will eat breakfast and then repeat blood draws 2.5 hours later. They will have a urine test.
- Blood and urine tests will be done at the end of the fast and after the meals to confirm that the participant fasted for the full 24-hour period.
- Participants will have lung function tests and exhaled gas measurements. A machine will measure the volume of air they can breathe out. Some gases in the breath increase with inflammation. Participants will breathe into a machine that analyzes the gases in their breath.
Detailed description
The NLRP3 inflammasome is part of the innate immune system that can be activated by atherosclerosis, gout and diabetes (sterile inflammation). As mitochondrial signaling can trigger the NLRP3 inflammasome, we initially proposed that fasting, via a nutrient-sensing mitochondrial program, would dampen this innate immune program. Our preliminary data shows that a 24-hour fasting does blunt NLRP3 inflammasome activation in healthy young individuals. Interestingly, this inflammasome program has been implicated in the pathophysiology of bronchoreactivity linked to asthma and intermittent fasting has been found to reduce disease exacerbations in asthmatic patients. The objective of this protocol will extend our investigations, from what we are finding in young control normal volunteers, to enable us to investigate stable mild-moderate asthmatic subjects to determine whether fasting can blunt inflammasome activation and assess whether this transient nutrient-deprivation maneuver can improve airflow. Blood samples and pulmonary function testing to assay the immune response and bronchoreactivity will be performed in subjects in response to a 24-hour fast (water intake will not be restricted) followed by re-testing 3 hours after a fixed caloric meal. The objective of this pilot study is to identify if these immune adaptive pathways can be subdued in human subjects with a known inflammasome linked disease. Additionally, this study may enable us to identify a potential therapeutic pathway to blunt/negate inflammation associated with nutrient-excess associated bronchoreactivity of asthma.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –stable mild-moderate asthmatic subjects |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- -Males and females between the ages of 18 and 60@@@-Asthmatic subjects will have a history consistent with asthma, be on chronic asthma therapy and have prior documentation of reversible airflow obstruction based upon either a positive response to an inhaled bronchodilator or a positive methacholine broncho-provocation challenge test@@@@@@
Key inclusion criteria (2 listed)
- Males and females between the ages of 18 and 60
- Asthmatic subjects will have a history consistent with asthma, be on chronic asthma therapy and have prior documentation of reversible airflow obstruction based upon either a positive response to an inhaled bronchodilator or a positive methacholine bronchoprovocation challenge test
Key exclusion criteria (4 listed)
- Subjects with concurrent acute illness or other chronic illnesses associated with inflammation including diabetes requiring medical management.
- 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.
- Medical condition identified by screening bloodwork that would preclude safe participation or valid data collection.
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
Change in IL-1-beta secretion in response to inflammasome stimulation in PBMCs comparing the fasted response to the fed response
Time frame: 24 hours
Determine whether the NLRP3 inflammasome is blunted by a 24-hour fast in PBMC s in subjects with mild to moderate asthma.Initiate 24-hour fast with the exception of drinking water and use of asthma medications until midnight. Patients will be asked to hold their asthma medications after midnight. Fasting research labs to study the inflammasome and Fed State Research Labs to study the inflammasome.
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 1 Feb 2021.
- Background: PubMed 21443539Besnard AG, Guillou N, Tschopp J, Erard F, Couillin I, Iwakura Y, Quesniaux V, Ryffel B, Togbe D. NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant. Allergy. 2011 Aug;66(8):1047-57. doi: 10.1111/j.1398-9995.2011.02586.x. Epub 2011 Mar 28.
- Background: PubMed 25356867Kim SR, Kim DI, Kim SH, Lee H, Lee KS, Cho SH, Lee YC. NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation. Cell Death Dis. 2014 Oct 30;5(10):e1498. doi: 10.1038/cddis.2014.460.
- Background: PubMed 24336249Kim HY, Lee HJ, Chang YJ, Pichavant M, Shore SA, Fitzgerald KA, Iwakura Y, Israel E, Bolger K, Faul J, DeKruyff RH, Umetsu DT. Interleukin-17-producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity. Nat Med. 2014 Jan;20(1):54-61. doi: 10.1038/nm.3423. Epub 2013 Dec 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, 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 2 inclusion and 4 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 1 Feb 2021. 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?
Change in IL-1-beta secretion in response to inflammasome stimulation in PBMCs comparing the fasted response to the fed 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 NCT02471300, which also lists 3 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 1 Feb 2021.