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

This study is currently recruiting participants.
Verified January 2013 by Brigham and Women's Hospital
Sponsor:
Information provided by (Responsible Party):
Frank M. Sacks, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01399632
First received: July 15, 2011
Last updated: January 14, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention
Overweight
Cardiovascular Diseases
 Behavioral: Low Fat and High Carbohydrate Diet
Behavioral: High Fat and Low Carbohydrate Diet

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Dietary Fat and High-Density Lipoprotein (HDL) Metabolism-Effect of Carbohydrate and Fat Intake

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • high-density lipoprotein (HDL) cholesterol [ Time Frame: Diet Periods I and II-Days 28-32 ] [ Designated as safety issue: No ]
    To determine how dietary unsaturated fat when it replaces carbohydrate affects HDL metabolism.


Secondary Outcome Measures:
  • To study HDL with apoE [ Time Frame: Diet Periods I and II-Days 28-32 ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Provide guidance for interpreting effects of unsaturated fats on reverse cholesterol transport [ Time Frame: Diet Periods I and II-Days 28-32 ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: August 2010
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Fat and Low Carbohydrate Diet Behavioral: High Fat and Low Carbohydrate Diet
High Fat and Low Carbohydrate Diet
Other Name: Diet and HDL Metabolism
Experimental: Low Fat and High Carbohydrate Diet Behavioral: Low Fat and High Carbohydrate Diet
Low Fat and High Carbohydrate Diet
Other Name: Diet and HDL Metabolism

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.

  Eligibility

Ages Eligible for Study:   21 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01399632

Contacts
Contact: Louise Bishop, BS lbishop@hsph.harvard.edu

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Louise M Bishop, BS         lbishop@hsph.harvard.edu    
Principal Investigator: Frank M Sacks, MD            
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Frank M Sacks, MD Harvard University/Brigham and Women's Hospital
  More Information

No publications provided

Responsible Party: Frank M. Sacks, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01399632     History of Changes
Other Study ID Numbers: HL095964
Study First Received: July 15, 2011
Last Updated: January 14, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on May 16, 2013