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

Healthy Volunteers Clinical Trial

— ENTHRALL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01250990
• Other study ID #: 811956
• Status: Completed
• Phase: N/A
• First received: November 29, 2010
• Last updated: November 21, 2011
• Start date: November 2010
• Est. completion date: May 2011

Study information

• Verified date: November 2011
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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:
• Placebo
Placebo

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint of this study is the determination of 3H cholesterol in the HDL fraction over time before and after treatment with niacin.		within 6 months of last patient last visit (LPLV)	No
Secondary	Identification of Factors that Predict the RCT Response	triglyceride and apolipoprotein kinetics in very low density lipoprotein (VLDL) and HDL by stable isotopes,; the acute insulin response to glucose during the frequently sampled intravenous glucose tolerance test (FSIGT),; fasting measures of lipid, fat, and carbohydrate metabolism.	Within 1 year of LPLV	No
Secondary	Clarification of Physiological Effects of Niacin	Nocturnal free fatty acid rebound as a mediator of peripheral, adipose, and hepatic insulin resistance by FSIGT; Clinical lipids/lipoprotein (a) (Lp(a)), adipokines, and clinical safety laboratory studies	within 1 year of LPLV	No
Secondary	Methods Refinement	3H cholesterol (as its metabolites) in the Non-HDL fraction, feces, and red blood cells; the intra-individual coefficient of variation in each parameter evaluated.	within 1 year of LPLV	No
Secondary	Clarification of Physiological Effects of Niacin	Nocturnal free fatty acid rebound as a mediator of peripheral, adipose, and hepatic insulin resistance by FSIGT; Clinical lipids/Lp(a), adipokines, and clinical safety laboratory studies	within 1 year of LPLV	No