Effects of Meal Macronutrients on Postprandial Lipids

Official title

Prospective Cross-Over Study of the Effects of Meal Macronutrients on Postprandial Lipids

Overview

Background: Abnormal fats in the blood can lead to many problems, including heart disease. Researchers want to learn more about how eating meals with different levels of nutrients affects fats in the blood. Specifically, they want to study people with too much body fat, too little body fat, and a kidney problem called nephrotic syndrome. Objective: To learn more about how different types of foods affect fat levels in the blood. Eligibility: People aged 18 years or older with a health condition that affects how their body handles fats. Healthy volunteers are also needed. Design: Participants will have 2 overnight stays in the clinic within 6 months. At each visit, after staying overnight, they will eat a breakfast casserole. At 1 visit, breakfast will be a high-fat, low carbohydrate meal. At the other, it will be a high-carbohydrate, low-fat meal. Participants will have a tube inserted into a vein in their arm. They will have blood drawn via the tube 12 times in 8 hours: 2 times before they eat the breakfast and 10 times after. Participants will have other tests during their stays: * A resting metabolic test captures the air they exhale and measures how much energy they use at rest. * A dual energy X-ray absorptiometry (DXA) scan measures how much fat and muscle they have. * A Fibroscan is a special type of ultrasound of the liver. * A body surface scan uses lasers to measure the total area of the body. * A bioelectric impedance (BIS) exam measures how fast small electric currents move through their body. Participants may opt to have a third visit. At this visit, the breakfast will be high in protein....

Detailed description

Study Description:

This is a single site, randomized cross-over study assessing the effects of different test meals of varying macronutrient composition on post-prandial lipid metabolism. Studies will be conducted in healthy individuals and in several patient populations including those with nephrotic syndrome (NS), lipodystrophy, and metabolic syndrome.

The study hypothesis is that the number, composition and kinetics of lipid-containing particles will differ in the post-prandial state:

1. Within subjects, comparing meals of differing macronutrient composition (i.e. high fat versus high carbohydrate) 2. Between subjects with different disorders (i.e., lipodystrophy vs. NS vs. healthy) 3. Within subjects before and after treatment of their underlying disorders (i.e. nephrotic vs non-nephrotic states)

Objectives:

* Primary Objective: Determine the difference in postprandial triglycerides between meals of different macronutrient composition within each study cohort. * Secondary Objective: Determine differences in post-prandial triglycerides between different study populations.

Endpoints:

* Primary Endpoint: Difference in baseline adjusted AUC for TG for 8 hours after meals of different macronutrient composition. * Secondary Endpoints: Difference in baseline adjusted AUC for TG for each meal test between study cohorts

Interventions

• Other High carb then high fat breakfast
  High carb then high fat breakfast
• Other High fat then high carb breakfast
  High fat then high carb breakfast

Primary outcome measures

• Determine the difference in postprandial triglycerides between meals of different macronutrient composition within each study cohort. [Time frame: 8 hours]

Secondary outcome measures (1)

• Determine differences in post-prandial triglycerides between different study populations. [Time frame: 8 hours]

Eligibility criteria

• INCLUSION CRITERIA:

Common inclusion criteria (all groups):

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Age >= 18 years
• Average alcohol intake in the past 6 months < 3 drinks (approximately 30g) per day (male) or < 2 drinks (approximately 20 g) per day (female)

Healthy control specific inclusion criteria:

• In good general health with no known active medical conditions as evidenced by medical history
• Fasting glucose <100 mg/dL
• HbA1c <5.7%
• Fasting triglycerides <150 mg/dL
• ALT and AST within normal limits
• BMI >=18.5 to <25 kg/m\^2 (or <23 kg/m\^2 in participants of Asian descent)
• Not taking any medications or supplements that, in the opinion of the investigator, would interfere with interpretation of study data.

Metabolic syndrome specific inclusion criteria

• Obesity defined as either

• BMI >30 kg/m\^2 (or >=27 kg/m\^2 in participants of Asian descent), OR
• Elevated waist circumference as defined below:

• Country/Ethnic group - Europid, Sub-Saharan African, Eastern Mediterranean and Middle East (Arab):

• Sex: Male; Waist circumference: >=94cm
• Sex: Female; Waist circumference: >=80cm
• Country/Ethnic group - South Asian, Chinese, Japanese, Ethnic South and Central American:

• Sex: Male; Waist circumference: >=90cm
• Sex: Female; Waist circumference: >=80cm

Plus any 2 of the following

• Elevated triglycerides defined as EITHER

• Fasting triglycerides >= 150 mg/dL at screening, OR
• Specific treatment for hypertriglyceridemia
• Low HDL cholesterol, defined as EITHER

• HDL <40 mg/dL (males) or <50 mg/dL (females) at screening, OR
• Specific treatment for low HDL
• Elevated blood pressure defined as EITHER

• Systolic BP >= 130 at screening, OR
• Diastolic BP >= 85 mm Hg at screening, OR
• Treatment of previously diagnosed hypertension
• Elevated glucose defined as EITHER

• HbA1c >= 5.7% (at screening), OR
• Fasting serum glucose >= 100 mg/dL (at screening), OR
• 2-hour post-load glucose levels >= 140 mg/dL (by history), OR
• Prior diagnosis of type 2 diabetes

Lipodystrophy-specific inclusion criteria:

• Clinical diagnosis of generalized or partial lipodystrophy based on reduction in adipose tissue outside the normal range in some or all adipose depots (including, at a minimum, the gluteofemoral depot).
• Insulin resistance as defined by fasting insulin >22.5 or high exogenous insulin requirement (> 2 units per kg per day or > 200 units total per day) at screening.

Nephrotic syndrome specific inclusion criteria

• History of biopsy proven non-diabetic glomerular disease (any histology)
• Nephrotic range proteinuria defined by ANY of the following:

• Protein/creatinine ratio uPCR >= 3.5 g/g at screening, OR
• 24 hour protein excretion >= 3.5 gr/24hr) at screening, OR
• History of nephrotic range proteinuria (as defined above) within the past 5 years but in complete (defined as proteinuria <= 0.3 g/day or partial remission (defined as a 50% or greater decrease in proteinuria compared to baseline and proteinuria < 3.5 g/day) based on 24 hr urine or uPCR at time of screening

Exclusion criteria

Common exclusion criteria (all groups):

An individual who meets any of the following criteria will be excluded from participation in this study:

• Consuming extreme macronutrient diet (e.g., very low-carbohydrate, high fat diets such as ketogenic, "paleo" or Atkins diets, among others).
• Plans to actively gain or lose weight during the study period (other than changes in water balance as clinically needed in subjects with nephrotic syndrome).
• Change in body weight of >5% or >3 kg (whichever is larger) in the 3 months prior to screening (by participant report) in participants who do NOT have nephrotic syndrome.
• Body weight >450 lbs (upper limit that can be accommodated by DXA scanner).
• Participating in a regular strenuous exercise program (> 2h/week of vigorous activity) as determined by volunteer report or evidence of vigorous exercising in order to lose weight, change body shape, or to counteract the effects of eating.
• Uncontrolled diabetes, defined as HbA1c >9% at screening.
• Lipemia defined as fasting or non-fasting triglycerides of >1000 mg/dL at screening.
• Renal dysfunction defined as eGFR <50 mL/min/1.73 m\^2 at screening.
• In participants with liver disease, history of decompensated advanced liver disease, defined as direct bilirubin > 0.5 g/dL, PT > 18 seconds, albumin < 3 g/dL, MELD score > 12, or history of ascites, encephalopathy, variceal bleeding, spontaneous bacterial

peritonitis or liver transplant.

• History of hypertriglyceridemia-induced pancreatitis within 3 months prior to screening.
• Positive pregnancy test or breastfeeding at screening.
• Clinically significant abnormalities in thyroid function, blood counts, as assessed by screening labs.
• Acute cardiovascular events within the past 6 months
• Anemia (Hgb <10 mg/dL in women or <12 mg/dL in men) at screening
• Food allergies or other dietary restrictions that could increase risk associated with test meals or cause the subject to be unwilling to consume test meals (i.e. celiac disease, vegan diets).
• Subjects with chronic diarrhea, gastric bypass or lap-band procedures, ostomies, bowel motility problems, or other known conditions that could affect intestinal fat absorption.
• Subjects treated with tamoxifen, estrogens, or progestins that have not been stable for >4 weeks prior to screening.
• Blood donation in the last 2 weeks or planned blood donation during the study
• Subjects requiring regular transfusions for any reason.
• Subjects with known gastroparesis
• Inability to adhere to Lifestyle Considerations throughout study duration.
• Inability of the subject to understand and the unwillingness to sign a written informed consent document.
• Unwillingness to comply with all study procedures and unavailable for the duration of the study
• Any other condition or medication which, in the opinion of the investigator, increases risk to the subject, prevents the subject from complying with study procedures, prevents the subject from completing the study, or interferes with the interpretation of study results.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• National Institutes of Health Clinical Center — Bethesda

Identifiers

NCT: NCT07313787 · 10002465 · 002465-DK

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗