Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    14-H-0103
Previous Study | Return to List | Next Study

Effect of Fasting on the NLRP3 Inflammasome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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) )

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.

Condition or disease
Cardiovascular Disease Inflammatory Disease

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 23 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Pilot Study to Evaluate the Effect of Fasting on the NLRP3 Inflammasome
Actual Study Start Date : April 21, 2014
Actual Primary Completion Date : March 6, 2017
Actual Study Completion Date : January 27, 2021

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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 37 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
-Males and females between the ages of 21 and 37@@@-BMI between 23.5 and 29
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02122575


Locations
Layout table for location information
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Layout table for investigator information
Principal Investigator: Michael N Sack, M.D. National Heart, Lung, and Blood Institute (NHLBI)
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT02122575    
Other Study ID Numbers: 140103
14-H-0103
First Posted: April 24, 2014    Key Record Dates
Last Update Posted: February 1, 2021
Last Verified: January 2021
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) ):
Inflammasome
Fasting
Sirt3
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiovascular Diseases