Effect of Fasting on the NLRP3 Inflammasome

NCT02122575 | Completed

• 2 other identifiers: 14010314-H-0103
• Study Type: observational
• Target: 23
• Locations: 1 country
• Sites: 1

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.

Conditions

Cardiovascular Disease; Inflammatory Disease

Keywords

Inflammasome; Fasting; Sirt3

Outcome Measures

Primary Outcomes (1)

• Determine whether the NLRP3 inflammasome is blunted by a 24 hours fast in PBMC's from normal volunteers.

  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 Outcomes (2)

• Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs.

  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.

  end of study

Study Arms (1)

1

Males and females between the ages of 21 and 37

Eligibility Criteria

• Age: 21 Years - 37 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Osborn O, Olefsky JM. The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med. 2012 Mar 6;18(3):363-74. doi: 10.1038/nm.2627.

  PMID: 22395709 BACKGROUND

• Haneklaus M, Gerlic M, Kurowska-Stolarska M, Rainey AA, Pich D, McInnes IB, Hammerschmidt W, O'Neill LA, Masters SL. Cutting edge: miR-223 and EBV miR-BART15 regulate the NLRP3 inflammasome and IL-1beta production. J Immunol. 2012 Oct 15;189(8):3795-9. doi: 10.4049/jimmunol.1200312. Epub 2012 Sep 14.

  PMID: 22984081 BACKGROUND

• Fontana 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.

  PMID: 15096581 BACKGROUND

• Traba J, Kwarteng-Siaw M, Okoli TC, Li J, Huffstutler RD, Bray A, Waclawiw MA, Han K, Pelletier M, Sauve AA, Siegel RM, Sack MN. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J Clin Invest. 2015 Nov 3;125(12):4592-600. doi: 10.1172/JCI83260.

  PMID: 26529255 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cardiovascular Diseases; Fasting

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior

Study Officials

• Michael N Sack, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: April 24, 2014
• Study Start: April 21, 2014
• Primary Completion: March 6, 2017
• Study Completion: January 27, 2021
• Last Updated: February 1, 2021

Record last verified: 2021-01

Locations

US (1)