Effects of Niacin On Fatty Acid Trapping

NCT ID: NCT01984073

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2019-12-31

Brief Summary

The purpose of this study is to understand whether a vitamin called NIcotinic ACid vitamIN (NIACIN for short, also known as vitamin B3) helps the body process dietary fat more efficiently. This is important because people with dyslipidemia have a problem with how they process fat, which raise the risk of heart disease.

Detailed Description

This study includes three phases, which each have a separate purpose. At this time, we are only recruiting for Phase 2. The purpose of this particular phase is to measure the effects of niacin after drinking a glass of heavy cream as a source of fat. We hope that studying the way the body responds will help us better understand how niacin works.

In this study, we are interested in niacin's ability to lower triglycerides, or fat in the blood. We are studying two different forms of niacin and comparing them to each other. The two forms differ in how long they take to release niacin into the bloodstream. The first form is called Nialor, and is sometimes called immediate-release niacin because it is absorbed into the bloodstream quickly. The second form is called Niaspan, and is sometimes called extended-release niacin because it is a time-released spansule that takes longer to get into the bloodstream. We are comparing the two forms because we think that the time that it takes to absorb niacin may affect how it works. We also want to understand one of the common effects of niacin: skin flushing. Most people who take niacin experience flushing, which is a hot flash. In this study, we are studying whether the two forms of niacin cause different degrees of flushing. Niaspan is approved by the US Food and Drug Administration (FDA) to treat unfavorable cholesterol levels and prevent heart attacks in those who have already suffered heart attacks. Nialor is available over the counter as a supplement and contains Silymarin (milk thistle) and Policosanol (an extract from sugar cane) in addition to niacin.

Conditions

Dyslipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

ER Niacin Oral Fat Challenge

ER Niacin (Niaspan) 2000mg one hour prior to Oral Fat Challenge using fresh cream at a dose of 50 g fat per square meter of body surface area. This is followed by frequent plasma and urine collections for next 12 hours to assess markers of fat metabolism and inflammation.

Group Type: ACTIVE_COMPARATOR

ER Niacin Oral Fat Challenge

Intervention Type: DRUG

Extended release niacin 2000 mg at hour 0, followed by oral fat challenge at hour 1.

IR Niacin Oral Fat Challenge

Immediate-Release Niacin (Nialor) 500 mg one hour prior to Oral Fat Challenge and again 1, 3 and 5 hours after the oral fat load for a total dose of 2 grams.Subjects will undergo plasma and urine collections for 12 hours to assess markers of fat metabolism and inflammation.

Group Type: ACTIVE_COMPARATOR

IR Niacin Oral Fat Challenge

Intervention Type: DRUG

Nialor(R) 500mg or Placebo at hour 0, 2, 4, and 6. Oral fat challenge at hour 1 (one hour after first dose of immediate-release niacin)

Placebo Oral Fat Challenge

Placebo one hour before and 1,3, and 5 hours after oral fat load using heavy cream at 50 grams of fat per square meter of body surface area. Plasma and urine collections for 12 hours

Group Type: PLACEBO_COMPARATOR

Placebo Oral Fat Challenge

Intervention Type: OTHER

Placebo at hour 0. Oral fat challenge at hour 1, followed by placebo at hours 2,4,and 6

Interventions

ER Niacin Oral Fat Challenge

Extended release niacin 2000 mg at hour 0, followed by oral fat challenge at hour 1.

Intervention Type: DRUG

IR Niacin Oral Fat Challenge

Nialor(R) 500mg or Placebo at hour 0, 2, 4, and 6. Oral fat challenge at hour 1 (one hour after first dose of immediate-release niacin)

Intervention Type: DRUG

Placebo Oral Fat Challenge

Placebo at hour 0. Oral fat challenge at hour 1, followed by placebo at hours 2,4,and 6

Intervention Type: OTHER

Other Intervention Names

Niaspan; Nialor

Eligibility Criteria

Inclusion Criteria

• Meet protocol defined criteria for atherogenic dyslipidemia phenotype
• Men and non-pregnant, non-lactating women between the ages of 22 and 75
• Fasting triglycerides <500 mg/dL
• Ability to understand and agree to informed consent
• Willingness to comply with study-related procedures

Exclusion Criteria

• Dysbetalipoproteinemia
• History of extreme triglyceridemia (TG >500 mg/dL) or pancreatitis from triglyceridemia, regardless of whether it is currently controlled
• LDL >190 mg/dL
• History of chronic renal insufficiency (serum creatinine >2.0 mg/dL)
• History of non-skin malignancy within the previous 5 years
• Subject reported history of HIV
• Uncontrolled thyroid disease
• Hypoalbuminemia (serum albumin >2.5 mg/dL)
• Exposure to an investigational drug within 6 weeks prior to the screening visit
• Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition
• Major surgery within the previous 6 weeks
• Subjects who have undergone any organ transplant
• History of drug abuse within the past 3 years, or regular alcohol use >14 drinks per week
• Women who are breast-feeding
• Women who are pregnant by urine pregnancy test at each 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
• Change in statin dose within 6 weeks of the first experimental visit
• Use of the following non-statin lipid-altering therapy within 6 weeks of the first experimental visit: Niacin > 100 mg/day (Niacor, Slo-Niacin, Niaspan, Advicor, or supplemental niacin), Fibrates [gemfibrozil (Lopid), fenofibrate (Antara, Lofibra, Tricor, Triglide)], Enterically active drugs [colestipol (Colestid), cholestyramine (Questran), colesevelam (Welchol), ezetimibe (Zetia, Vytorin)], Red yeast rice, Fish oil (Omacor, numerous supplements)
• Use of medications indicated for the treatment of diabetes within 6 weeks of the screening visit
• Known intolerance or contraindication to niacin (e.g., moderate to severe gout, severe peptic ulcer disease)
• Medical condition that would prohibit fasting (e.g., diagnosis of insulinoma or postabsorptive hypoglycemia)
• Significant disinclination to dairy products (e.g., lactose intolerance, inviolable dietary restrictions)
• History of anaphylactic reaction
• For indocyanine green substudy: iodine allergy or shellfish allergy (n.b. a subject with an allergy can participate in the overall experiment, but will forego the indocyanine green tracer study)
• Donation of blood 8 weeks and/or treatment with medications for psychiatric disorders
• Hemoglobin <10 g/dL

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Arizona Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Richard Dunbar

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard L Dunbar, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Presbyterian Hospital

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

K23HL091130

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NOFAT

Identifier Type: -

Identifier Source: org_study_id