Effect of Fasting on the NLRP3 Inflammasome

January 29, 2021 updated by: National Heart, Lung, and Blood Institute (NHLBI)

Pilot Study to Evaluate the Effect of Fasting on the NLRP3 Inflammasome

Background:

- Restricting calories can help a person reduce risk factors for heart disease. Researchers have found that not eating or drinking anything but water for 24 hours prevents the activation of a component of the immune system, called the inflammasome. The inflammasome is associated with the development of diabetes and heart disease. Researchers want to learn more about the body s response to fasting.

Objective:

- To explore the benefits of calorie restriction on heart health.

Eligibility:

- Healthy adults ages 21 32 with a body mass index between 26 and 29.

Design:

  • Participants will be screened with a medical history, physical exam and blood test.
  • Participants will not eat or drink after 10 p.m. before their first visit.
  • Participants have breakfast at the clinic. The breakfast will be about 500 calories. Then they will not eat or drink (except water) for 24 hours.
  • Participants will return to the clinic the next morning. They will have blood drawn. Then they will have breakfast. Blood will be drawn again at 1 hour and 3 hours after the meal.
  • Blood and urine tests at the end of the fast and following the meals will be done to confirm that participants have fasted for the full 24-hour period.

Study Overview

Status

Completed

Conditions

Detailed Description

A caloric restricted diet has numerous health effects including the reduction in numerous cardiovascular disease risk factors. The cellular programs activated by caloric restriction are similarly turned on in preclinical 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 immune system, termed the inflammasome, which is associated with the development of diabetes and atherosclerosis. We would like to study the inflammasome in human blood cells to evaluate whether the beneficial immune effects of fasting/caloric restriction are operational in humans. Blood samples to test the immune response will be collected in subjects 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 these immune adaptive pathways can be activated in human subjects as a possible readout to test whether this pathway could be investigated as a therapeutic target to blunt/negate the inflammation associated with nutrient-excess associated diseases such as diabetes and/or atherosclerosis.

Study Type

Observational

Enrollment (Actual)

23

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 States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

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

Ages Eligible for Study

21 years to 37 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

-Males and females between the ages of 21 and 37@@@-BMI between 23.5 and 29

Description

  • INCLUSION CRITERIA:

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 between 23.5 and 29

EXCLUSION CRITERIA:

  • 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 <23.5 or >29
  • 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

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

Cohorts and Interventions

Group / Cohort
1
Males and females between the ages of 21 and 37

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine whether the NLRP3 inflammasome is blunted by a 24 hours fast in PBMC's from normal volunteers.
Time Frame: 24 hours
The primary outcome will be the change in IL-1 secretion in response to inflammasome stimulation in PBMC s comparing the fasted response to the fed response. As there are two fed responses, we will initially determine whether inflammasome induction differs between the peak post- prandial insulin effect (1 hr) and the peak post-prandial fatty acid levels (3 hr). The higher mean IL-1 levels between the two fed states will be considered the index fed response and will be compared to the fasting levels as the primary outcome. 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.
24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs.
Time Frame: end of study
4. Determination of Sirt3 levels and downstream programs in the different nutrient states in PBMC cell samples.
end of study
Determine whether serum from subjects in fasted state will blunt the inflammasome compared to serum from the fed stat in a human transformed macrophage cell line.
Time Frame: end of study
Analysis of difference in inflammasome between the different fed states. Analysis of the inflammasome effect of fed versus fasted serum on transformed THP-1 cells.
end of study

Collaborators and Investigators

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

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

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

Helpful Links

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)

April 21, 2014

Primary Completion (Actual)

March 6, 2017

Study Completion (Actual)

January 27, 2021

Study Registration Dates

First Submitted

April 23, 2014

First Submitted That Met QC Criteria

April 23, 2014

First Posted (Estimate)

April 24, 2014

Study Record Updates

Last Update Posted (Actual)

February 1, 2021

Last Update Submitted That Met QC Criteria

January 29, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 140103
  • 14-H-0103

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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