Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02122575
Other study ID # 140103
Secondary ID 14-H-0103
Status Completed
Phase
First received
Last updated
Start date April 21, 2014
Est. completion date January 27, 2021

Study information

Verified date January 2021
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 23
Est. completion date January 27, 2021
Est. primary completion date March 6, 2017
Accepts healthy volunteers No
Gender All
Age group 21 Years to 37 Years
Eligibility - 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 Design


Locations

Country Name City State
United States National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Epub 2004 Apr 19. — View Citation

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-1ß production. J Immunol. 2012 Oct 15;189(8):3795-9. doi: 10.4049/jimmunol.1200312. Epub 2012 Sep 14. — View Citation

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. Review. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Evaluate whether these effects are associated with activation of the Sirt3 and its canonical mitochondrial adaptive programs. 4. Determination of Sirt3 levels and downstream programs in the different nutrient states in PBMC cell samples. end of study
Secondary 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. 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
See also
  Status Clinical Trial Phase
Completed NCT02122198 - Vascular Mechanisms for the Effects of Loss of Ovarian Hormone Function on Cognition in Women N/A
Completed NCT02502812 - Bioequivalence Study of Clopidogrel 75 mg in Two Tablet Formulations Relative to Reference Tablet in Healthy Subjects Phase 1
Recruiting NCT04216342 - Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Fx-5A in Healthy Volunteers Phase 1
Completed NCT03654313 - Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus Phase 1
Completed NCT03646656 - Heart Health Buddies: Peer Support to Decrease CVD Risk N/A
Completed NCT02081066 - Identification of CETP as a Marker of Atherosclerosis N/A
Completed NCT02147626 - Heart Health 4 Moms Trial to Reduce CVD Risk After Preeclampsia N/A
Not yet recruiting NCT06405880 - Pharmacist Case Finding and Intervention for Vascular Prevention Trial N/A
Recruiting NCT03095261 - Incentives in Cardiac Rehabilitation N/A
Not yet recruiting NCT02578355 - National Plaque Registry and Database N/A
Completed NCT02711878 - Healing Hearts and Mending Minds in Older Adults Living With HIV N/A
Completed NCT02589769 - Effects of Reduction in Saturated Fat on Cholesterol and Lipoproteins in Lean and Obese Persons N/A
Completed NCT02868710 - Individual Variability to Aerobic Exercise Training N/A
Completed NCT02998918 - Effects of Short-term Curcumin and Multi-polyphenol Supplementation on the Anti-inflammatory Properties of HDL N/A
Recruiting NCT02885792 - Coronary Artery Disease in Patients Suffering From Schizophrenia N/A
Completed NCT02640859 - Investigation of Metabolic Risk in Korean Adults
Completed NCT02652975 - Anticancer Treatment of Breast Cancer Related to Cardiotoxicity and Dysfunctional Endothelium N/A
Completed NCT02657382 - Mental Stress Ischemia: Biofeedback Study N/A
Completed NCT02272946 - Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk Phase 2
Recruiting NCT02265250 - Pilot Study-Magnetic Resonance Imaging for Global Atherosclerosis Risk Assessment