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Effect of Niacin on Transport of HDL and Relationship to Atherogenic Lipoproteins and Lipolysis (ENTHRALL)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Amanda Baer, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01250990
First received: November 29, 2010
Last updated: November 21, 2011
Last verified: November 2011
  Purpose

This study looks at whether niacin improves reverse cholesterol transport (RCT) in healthy volunteers. 3H-Cholesterol will be used to measure RCT by analyzing changes in the tracer activity in total plasma, lipoproteins, red blood cells (RBCs) and stool. The hypothesis is that niacin augments reverse cholesterol transport.


Condition Intervention
Healthy Volunteers
Drug: Niacin
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: A Randomized, Double-Blind, Placebo Controlled Study Evaluating the Effects Of Niacin On Reverse Cholesterol Transport As Measured Using 3H Particulate Cholesterol in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • The primary endpoint of this study is the determination of 3H cholesterol in the HDL fraction over time before and after treatment with niacin. [ Time Frame: within 6 months of last patient last visit (LPLV) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Identification of Factors that Predict the RCT Response [ Time Frame: Within 1 year of LPLV ] [ Designated as safety issue: No ]
    1. triglyceride and apolipoprotein kinetics in very low density lipoprotein (VLDL) and HDL by stable isotopes,
    2. the acute insulin response to glucose during the frequently sampled intravenous glucose tolerance test (FSIGT),
    3. fasting measures of lipid, fat, and carbohydrate metabolism.

  • Clarification of Physiological Effects of Niacin [ Time Frame: within 1 year of LPLV ] [ Designated as safety issue: No ]
    1. Nocturnal free fatty acid rebound as a mediator of peripheral, adipose, and hepatic insulin resistance by FSIGT
    2. Clinical lipids/lipoprotein (a) (Lp(a)), adipokines, and clinical safety laboratory studies

  • Methods Refinement [ Time Frame: within 1 year of LPLV ] [ Designated as safety issue: No ]
    1. 3H cholesterol (as its metabolites) in the Non-HDL fraction, feces, and red blood cells
    2. the intra-individual coefficient of variation in each parameter evaluated.

  • Clarification of Physiological Effects of Niacin [ Time Frame: within 1 year of LPLV ] [ Designated as safety issue: No ]
    1. Nocturnal free fatty acid rebound as a mediator of peripheral, adipose, and hepatic insulin resistance by FSIGT
    2. Clinical lipids/Lp(a), adipokines, and clinical safety laboratory studies


Enrollment: 20
Study Start Date: November 2010
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Niacin
Niacin taken orally for 12 weeks at the highest tolerated dose (up to 6 grams), and at least 2 grams daily and up to the maximum approved dose. Subjects will initiate therapy with Niaspan and will advance to Niacor as tolerated.
Drug: Niacin
Niacin taken orally for 12 weeks at the highest tolerated dose (up to 6 grams), and at least 2 grams daily and up to the maximum approved dose. Subjects will initiate therapy with Niaspan and will advance to Niacor as tolerated.
Other Name: Niacor and Niaspan
Placebo Comparator: Placebo Other: Placebo
Placebo

Detailed Description:

The study will use 3H-cholesterol bound to albumin (particulate cholesterol) to assess the ability of high density lipoprotein (HDL) to transport cholesterol to the liver to be eliminated. This process is called Reverse Cholesterol transport and is one of the main mechanisms by which HDL protect against atherosclerotic cardiovascular disease. The availability of a method to assess RCT is important for the development of new drugs which affect RCT and may result in useful treatments for atherosclerosis.

This study will evaluate the use of radiolabeled particulate cholesterol administered intravenously in association with albumin, as a method to study reverse cholesterol transport (RCT) in humans before and after treatment by niacin by analyzing changes in the tracer activity in total plasma and lipoproteins. The study population is healthy volunteers.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men and women between the ages of 18 and 75 inclusive
  • HDL cholesterol >= 25 mg/dL in all subjects, and <= 60 mg/dL in men and <= 70 mg/dL in women
  • Women must be of non-childbearing potential. They must have been surgically sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal women must have no regular menstrual bleeding for at least 2 years prior to inclusion.
  • Subjects must be in good overall health.
  • Subjects must be able to comprehend and willing to provide a signed Institutional Regulatory Board (IRB) approved Informed Consent Form.
  • Subjects must be willing to comply with all study-related procedures.
  • Subjects must weigh at least 140 pounds to participate in the HDL kinetics Substudy.

Exclusion Criteria:

  • Clinically-manifest cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
  • History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit
  • Presence of New York Heart Association (NYHA) Class III or IV chronic heart failure or unstable angina pectoris
  • History of any other endocrine disease
  • History of a non-skin malignancy within the previous 5 years
  • Anemia defined as hemoglobin less than 12 g/dL
  • Renal insufficiency as defined by creatinine ³ 1.3 mg/dl
  • Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition
  • Uncontrolled hypertension (Systolic >160 mm Hg and/or Diastolic >100 mmHg on two consecutive measurements
  • Use of warfarin, or any known coagulopathy and /or elevated Prothrombin time/Partial Thromboplastin Time (PT/PTT) >1.5 x upper limit of normal (ULN)
  • Self-reported history of Human immunodeficiency virus (HIV) positive
  • Previous organ transplantation
  • Clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x ULN, or self-reported history of positive for Hepatitis B or Hepatitis C
  • Any major surgical procedure that occurred within the previous 3 months of the screening visit
  • History of illicit drug abuse (< 1 year)
  • Regular use of alcoholic beverages (> 2 drinks/day)
  • Body mass index (BMI) > 35 kg/m2 or < 18.5 kg/m2
  • Administration of an investigational drug within 6 weeks prior to the screening visit
  • Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study will be excluded.
  • Use of daily lipid-altering therapy prior to the initiation of study medication is exclusionary under the following circumstances (washout of non-statins is permitted):

    • Statins within 4 weeks
    • Niacin > 250 mg/ day within 6 weeks: Advicor, Niaspan, Niacor, Simcor, Slo-Niacin, or supplemental niacin
    • Fibrates within 12 weeks: fenofibrate (Antara, Lofibra, Tricor, Triglide), gemfibrozil (Lopid), or clofibrate
    • Enterically active lipid-altering drugs within 4 weeks: colestipol (Colestid), cholestyramine (Questran), colesevelam (Welchol), ezetimibe (Zetia, Vytorin), orlistat (Xenical, Alli)
    • Red yeast rice
    • Fish oil > 2 g/day within 4 weeks: Lovaza (née Omacor), numerous supplements
    • Altered dose of a selective estrogen receptor modulator (SERM) within 4 weeks
  • History of severe intolerance of niacin
  • Men who plan to conceive a child within 3 months of the conclusion of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01250990

Locations
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Richard Dunbar, MD MSTR University of Pennsylvania
  More Information

No publications provided

Responsible Party: Amanda Baer, Project Manager, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01250990     History of Changes
Other Study ID Numbers: 811956
Study First Received: November 29, 2010
Last Updated: November 21, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
Healthy Volunteers

Additional relevant MeSH terms:
Niacin
Niacinamide
Nicotinic Acids
Antimetabolites
Cardiovascular Agents
Growth Substances
Hypolipidemic Agents
Lipid Regulating Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Vasodilator Agents
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on November 25, 2014