Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake

Cardiovascular Diseases Clinical Trial

Official title:

Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01399632
• Other study ID #: HL095964
• Status: Completed
• Phase: N/A
• First received: July 15, 2011
• Last updated: July 5, 2016
• Start date: August 2010
• Est. completion date: December 2013

Study information

• Verified date: July 2016
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

Generally, people with low levels of high-density lipoprotein (HDL) in blood are more likely to get heart disease than those who have normal or high levels. Dietary fat, whether the harmful type (saturated) or beneficial type (unsaturated) raises HDL levels. Dietary carbohydrate lowers HDL. The investigators are doing this research study to find out why the amount of HDL in a person's blood is affected by dietary unsaturated fat and carbohydrate. The investigators will trace the ability of the HDL in a person's blood to take up cholesterol, get bigger, and then leave the blood by passing into the liver. The investigators want to know if dietary unsaturated fat improves the ability of HDL to do this compared to dietary carbohydrate.

Description:

The investigators will study the kinetics of multiple types of high-density lipoprotein (HDL) in humans under two strictly controlled dietary conditions, high unsaturated fat and high carbohydrate, in 20 individuals with low HDL cholesterol and overweight or obesity. The participants will be given the controlled diets for 4 weeks in a randomized crossover design. They will be admitted to the Brigham & Women's Hospital Center for Clinical Investigation (CCI) the morning of Day 28 when they will be infused intravenously with a stable isotope tracer, trideuterated (D3), leucine for 10 minutes as a bolus. Blood will be sampled in the hospital through 24 hours, and thereafter at the ambulatory clinical center throughout 94 hours. HDL subtypes will be prepared in Dr. Sacks's laboratory at Harvard School of Public Health (HSPH) and analyzed for content of lipids and proteins, and for incorporation of the tracer into apolipoprotein A-I, the principal protein of HDL. These data will be studied by interactive modeling to a multi-compartment model of human HDL physiology that best fits the observed data. The model will yield HDL metabolic rates during unsaturated fat and carbohydrate-rich diets which will be tested for statistical significance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 21 Years to 75 Years

Eligibility

Inclusion Criteria:

• Only accepting participants in the Boston, Massachusetts area

• Age 21 to 75, male or female

• Willingness to eat prescribed diet for 4 weeks prior to infusion date, and 3.5 days after the infusion date

• Willingness to participate in an infusion protocol, which will require them to stay at the Center for Clinical Investigation (CCI) for one night and return for blood draws every day for the next 3 days.

• Body Mass Index (BMI) 25-35 Kg/m2

• HDL<45 mg/dL for men, <55 mg/dL for women

Exclusion Criteria:

• Hematocrit <33

• Low-density Lipoprotein (LDL) cholesterol >190 mg/dl

• HDL cholesterol <20 mg/dl, to exclude those with rare genetic HDL deficiency syndromes

• Fasting Triglycerides >500 mg/dl to exclude those with risk of pancreatitis

• ApoE genotypes, E2E2, E2E4, and E4E4.

• Lipid lowering medications

• Hormone replacement therapy

• Other medicines that affect plasma lipid levels: e.g. beta blockers, certain psychiatric medicines including Alprazolam, Chlordiazepoxide, Clonazepam, Diazepam, Lorazepam, Oxazepam, Prazepam, Aripiprazole, Chlorpromazine, Chlorprothixene, Clozapine, Flupenthixol, Fluphenazine, Haloperidol, Loxapine, Mesoridazine, Methotrimeprazine, Molindone, Olanzapine, Perphenazine, Pimozide, Pipotiazine, Prochlorperazine, Promazine, Promethazine, Quetiapine, Risperidone, Sulpiride, Thioridazine, Thiothixene, Trifluoperazine, Ziprasidone.

• Thyrotrophin-stimulating hormone: <0.5 or >5.0

• alanine aminotransferase : 1.5 x uln or 60 IU/L

• Aspartate transaminase: 1.5 x uln or 60 IU/L

• Bilirubin: outside upper limit. (>1.2 mg/dL)

• Creatinine: outside upper limit (>1.00 mg/dL)

• Diabetes by history

• Diabetes by fasting or post-challenge glycemia according to ADA guidelines:

• Fasting hyperglycemia (glucose >126 mg/dl).

• Post-challenge glucose by standard oral glucose tolerance test, >200 mg/dl

• Will not eat the provided diet and abstain from alcoholic beverages.

• Women who are pregnant

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Overweight

Intervention

Behavioral:
• Low Fat and High Carbohydrate Diet
Low Fat and High Carbohydrate Diet
• High Fat and Low Carbohydrate Diet
High Fat and Low Carbohydrate Diet

Locations

Country	Name	City	State
United States	Harvard T. H. Chan School of Public Health	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Brigham and Women's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Provide guidance for interpreting effects of unsaturated fats on reverse cholesterol transport		Diet Periods I and II-Days 28-32	No
Primary	high-density lipoprotein (HDL) cholesterol	To determine how dietary unsaturated fat when it replaces carbohydrate affects HDL metabolism.	Diet Periods I and II-Days 28-32	No
Secondary	To study HDL with apoE		Diet Periods I and II-Days 28-32	No