Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia

NCT07715890 | Not Yet Recruiting

• 2 other identifiers: 10002623002623-H
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Obesity is known to lead to diseases such as diabetes and high cholesterol (or fats) in the blood (hyperlipidemia). But no one knows why. Researchers think that high levels of fat in the blood may block important nutrients, such as vitamin E, from reaching places they are needed in the body. Objective: To learn how high-fat meals affect levels of vitamin E in the blood. Eligibility: People aged 18 to 65 with high blood fat levels. Healthy volunteers are also needed. Design: Participants will have 3 or 4 clinic visits in 3 months. The last visit will require them to stay in the clinic for 2 nights. Participants will be screened. They will have a physical exam and blood tests. After this visit, all participants must stop taking any dietary supplements. Those who use them must also stop taking any drugs to lower their blood sugar and blood fats. These participants will have an extra visit for blood tests after 60 days. The next visit will include 2 imaging scans: Magnetic resonance imaging (MRI) of the abdomen. This scan will check for fat in the liver. Dual-energy X-ray absorptiometry (DEXA). This scan measures the levels of body fat. On day 1 of the clinic stay, participants will have 2 set meals, with nothing but water after 10 pm. On day 2, they will drink high-fat shakes at 8 am, noon, and 4 pm. They will have blood draws every hour for 17 hours, and then every 2 hours until 7 am. The blood will be taken from a tube inserted into a vein and left in place for the day. On day 3, they will go home.

Conditions

Lipid Metabolism Disorders

Keywords

Vitamin E; Vitamin K; Vitamin D; Vitamin C; Postprandial; Fat meal; Sequestration; Hypertriglyceridemia; Fat-Soluble Vitamins; gamma tocopherol

Outcome Measures

Primary Outcomes (1)

• AUC (Area Under the Curve) of vitamin E plasma from hour 1 to hour 23 by cohort.

  Compare the effects of postprandial hypertriglyceridemia on plasma vitamin E dynamics in subjects between baseline normo- and hyperlipidemia.

  From hour 1 to hour 23

Secondary Outcomes (1)

• AUC of gamma-tocopherol, phylloquinone [K1]; menaquinone [K2]; 25-OH vitamin D; retinol [A] from hour 1 to hour 23 by cohort.

  From hour 1 to hour 23

Study Arms (2)

Healthy subjects

ACTIVE COMPARATOR

Three consecutive high-fat vitamin E-stripped meals

Dietary Supplement: High fat liquid shake

Subjects with hyperlipidemia

EXPERIMENTAL

Three consecutive high-fat vitamin E-stripped meals

Dietary Supplement: High fat liquid shake

Interventions

High fat liquid shake DIETARY_SUPPLEMENT

Three consecutive high-fat vitamin E-stripped meals

Healthy subjects; Subjects with hyperlipidemia

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1
• Males and females between the ages of 18 to 65
• BMI 18.5 - 26.9 kg/m\^2
• Subject understands the protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up instructions and evaluations
• Normotensive, not on medications for hypertension
• Not on glucose-lowering or lipid-lowing medications
• Screening labs with baseline HbA1c \<5.7%, baseline fasting triglyceride \< 150 mg/dL and LDL \<100 mg/dL
• Liver fat \<2%
• Cohort 2
• Males and females between the ages of 18 to 65
• BMI \>26 kg/m\^2 and \<36 kg/m\^2
• Subject understands the protocol and provides written, informed consent in addition to a willingness to comply with specified follow-up instructions and evaluations.
• Screening labs with baseline HbA1c \<= 7.5%, agree to be off or stop oral glucose-lowering medications (metformin), baseline fasting triglyceride \< 500 mg/dL and LDL \<190 mg/dL, agree to be off or stop oral lipid-lowing medications for 4-10 weeks prior to the inpatient visit.
• Liver fat \<2%

You may not qualify if:

• For women: pregnancy or currently breastfeeding
• Subjects \<18-year-old. This age group has a broad spectrum of hormonal profiles, due to development and puberty, which significantly increases the heterogenicity of the study subjects.
• Subjects \>65-year-old. This age group has significantly increased risk of cardiovascular diseases. To minimize the risk from temporarily suspending lipid- and glucose-lowering medications and stress from serial blood draws, we exclude these individuals.
• Heavy alcohol user (males with \>2 drinks per day or \>14 drinks per week; female with \>1 drinks per day or \>7 drinks per week)
• Current smoker, or former smoker who quit smoking \<15 years ago
• Subjects with weight changes greater than 20% baseline body weight over the past 3 months
• Subjects with lactose intolerance unwilling to take lactase
• Subjects with type 1 diabetes
• Subjects with hemoglobin \<11 g/dL or hematocrit \<33%
• Subjects with abnormal liver function test results
• Subjects with liver fat \>= 2% on abdominal MRI
• Subjects with a history of pancreatitis, diabetes ketoacidosis, hyperosmolar hyperglycemic state, advanced atherosclerosis, cardiovascular diseases, kidney diseases, or liver diseases
• Subjects with fat malabsorption including: history of gastrointestinal surgery, pancreatic insufficiency, inflammatory bowel disease, celiac disease, moderate-to-severe irritable bowel syndrome, and pathologic mutations impacting lipoprotein metabolism
• Subjects on glucocorticoids \>1 week (not including topical glucocorticoids)
• Subjects with HIV

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Traber MG, Leonard SW, Ebenuwa I, Violet PC, Wang Y, Niyyati M, Padayatty S, Tu H, Courville A, Bernstein S, Choi J, Shamburek R, Smith S, Head B, Bobe G, Ramakrishnan R, Levine M. Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled alpha-tocopherols in a 3-phase crossover design. Am J Clin Nutr. 2019 Nov 1;110(5):1148-1167. doi: 10.1093/ajcn/nqz172.

  PMID: 31495886 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lipid Metabolism Disorders; Hypertriglyceridemia

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperlipidemias; Dyslipidemias

Study Officials

• Robert D Shamburek, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine C Roskom, R.N.

CONTACT

(301) 451-7094; katherine.roskom@nih.gov

Robert D Shamburek, M.D.

CONTACT

(301) 496-3460; bobs@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2026
• First Posted: July 21, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: July 31, 2026

Record last verified: 2026-07-21

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning following de-identification and publication of the primary results, or other prespecified time point, and continuing for as long as the repository or access mechanism remains available.
• Access Criteria: Access to de-identified individual participant data will be determined based on the sensitivity of the data and disclosure risk. Data appropriate for broad sharing may be deposited in an open-access repository. Data requiring additional protections may be made available through a controlled-access mechanism subject to review and any applicable agreements.

Locations

US (1)