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Trial record 1 of 1 for:    14-H-0103
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Effect of Fasting on the NLRP3 Inflammasome

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ClinicalTrials.gov Identifier: NCT02122575
Recruitment Status : Completed
First Posted : April 24, 2014
Last Update Posted : February 1, 2021
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )

Tracking Information
First Submitted Date April 23, 2014
First Posted Date April 24, 2014
Last Update Posted Date February 1, 2021
Actual Study Start Date April 21, 2014
Actual Primary Completion Date March 6, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 17, 2019)
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.
Original Primary Outcome Measures
 (submitted: April 23, 2014)
Determine whether the NLRP3 inflammasome is blunted by a 24 hours fast in PBMC's from normal volunteers. [ Time Frame: 24 hours ]
Change History
Current Secondary Outcome Measures
 (submitted: January 8, 2020)
  • 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.
  • 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.
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Effect of Fasting on the NLRP3 Inflammasome
Official Title Pilot Study to Evaluate the Effect of Fasting on the NLRP3 Inflammasome
Brief Summary

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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population -Males and females between the ages of 21 and 37@@@-BMI between 23.5 and 29
Condition
  • Cardiovascular Disease
  • Inflammatory Disease
Intervention Not Provided
Study Groups/Cohorts 1
Males and females between the ages of 21 and 37
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 23, 2016)
23
Original Estimated Enrollment
 (submitted: April 23, 2014)
20
Actual Study Completion Date January 27, 2021
Actual Primary Completion Date March 6, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria
  • 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
Sex/Gender
Sexes Eligible for Study: All
Ages 21 Years to 37 Years   (Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT02122575
Other Study ID Numbers 140103
14-H-0103
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
Study Sponsor National Heart, Lung, and Blood Institute (NHLBI)
Collaborators Not Provided
Investigators
Principal Investigator: Michael N Sack, M.D. National Heart, Lung, and Blood Institute (NHLBI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date January 2021