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

Primary Purpose

Overweight, Cardiovascular Diseases

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Low Fat and High Carbohydrate Diet

High Fat and Low Carbohydrate Diet

About this trial

This is an interventional prevention trial for Overweight

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Harvard T. H. Chan School of Public Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

High Fat and Low Carbohydrate Diet

Low Fat and High Carbohydrate Diet

Arm Description

Outcomes

Primary Outcome Measures

high-density lipoprotein (HDL) cholesterol

To determine how dietary unsaturated fat when it replaces carbohydrate affects HDL metabolism.

Secondary Outcome Measures

To study HDL with apoE

Full Information

NCT ID

NCT01399632

First Posted

July 15, 2011

Last Updated

July 5, 2016

Sponsor

Brigham and Women's Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01399632

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Completed

Study Start Date

August 2010 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Overweight, Cardiovascular Diseases

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

High Fat and Low Carbohydrate Diet

Arm Type

Experimental

Arm Title

Low Fat and High Carbohydrate Diet

Arm Type

Experimental

Intervention Type

Behavioral

Intervention Name(s)

Low Fat and High Carbohydrate Diet

Other Intervention Name(s)

Diet and HDL Metabolism

Intervention Description

Low Fat and High Carbohydrate Diet

Intervention Type

Behavioral

Intervention Name(s)

High Fat and Low Carbohydrate Diet

Other Intervention Name(s)

Diet and HDL Metabolism

Intervention Description

High Fat and Low Carbohydrate Diet

Primary Outcome Measure Information:

Title

high-density lipoprotein (HDL) cholesterol

Description

To determine how dietary unsaturated fat when it replaces carbohydrate affects HDL metabolism.

Time Frame

Diet Periods I and II-Days 28-32

Secondary Outcome Measure Information:

Title

To study HDL with apoE

Time Frame

Diet Periods I and II-Days 28-32

Other Pre-specified Outcome Measures:

Title

Provide guidance for interpreting effects of unsaturated fats on reverse cholesterol transport

Time Frame

Diet Periods I and II-Days 28-32

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Frank M Sacks, MD

Organizational Affiliation

Harvard University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Harvard T. H. Chan School of Public Health

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

30944249

Citation

Morton AM, Furtado JD, Mendivil CO, Sacks FM. Dietary unsaturated fat increases HDL metabolic pathways involving apoE favorable to reverse cholesterol transport. JCI Insight. 2019 Apr 4;4(7):e124620. doi: 10.1172/jci.insight.124620. eCollection 2019 Apr 4.

Results Reference

derived

PubMed Identifier

29467335

Citation

Morton AM, Koch M, Mendivil CO, Furtado JD, Tjonneland A, Overvad K, Wang L, Jensen MK, Sacks FM. Apolipoproteins E and CIII interact to regulate HDL metabolism and coronary heart disease risk. JCI Insight. 2018 Feb 22;3(4):e98045. doi: 10.1172/jci.insight.98045. eCollection 2018 Feb 22.

Results Reference

derived

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

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