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Effects of Niacin On Fatty Acid Trapping (NOFAT)

Primary Purpose

Dyslipidemia

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ER Niacin Oral Fat Challenge

IR Niacin Oral Fat Challenge

Placebo Oral Fat Challenge

About this trial

This is an interventional other trial for Dyslipidemia focused on measuring Atherogenic dyslipidemia phenotype

Eligibility Criteria

22 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Hospital of the University of Pennsylvania
Presbyterian Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

ER Niacin Oral Fat Challenge

IR Niacin Oral Fat Challenge

Placebo Oral Fat Challenge

Arm Description

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.

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.

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

Outcomes

Primary Outcome Measures

Plasma Triglycerides

Plasma Triglycerides (TGs) after oral fat challenge will be measured to assess post-prandial lipidemia after niacin and placebo. Parameters of interest are the area under the curve (AUC), time to peak (t-max), and peak concentration (c-max). The relevant units will be mg.h/dl for plasma triglyceride AUC, minutes for time to peak plasma TG and mg/dl for c-max.

Secondary Outcome Measures

Full Information

NCT ID

NCT01984073

First Posted

November 7, 2013

Last Updated

July 8, 2020

Sponsor

University of Pennsylvania

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Arizona Pharmaceuticals Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01984073

Brief Title

Effects of Niacin On Fatty Acid Trapping

Acronym

NOFAT

Official Title

Effect of Niacin On Fatty Acid Trapping

Study Type

Interventional

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

December 2019 (Actual)

Study Completion Date

December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pennsylvania

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Arizona Pharmaceuticals Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

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

Dyslipidemia

Keywords

Atherogenic dyslipidemia phenotype

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ER Niacin Oral Fat Challenge

Arm Type

Active Comparator

Arm Description

Arm Title

IR Niacin Oral Fat Challenge

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo Oral Fat Challenge

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

ER Niacin Oral Fat Challenge

Other Intervention Name(s)

Niaspan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

IR Niacin Oral Fat Challenge

Other Intervention Name(s)

Nialor

Intervention Description

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

Other

Intervention Name(s)

Placebo Oral Fat Challenge

Intervention Description

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

Primary Outcome Measure Information:

Title

Plasma Triglycerides

Description

Time Frame

Baseline to 12 hour post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

22 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard L Dunbar, MD

Organizational Affiliation

University of Pennsylvania

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hospital of the University of Pennsylvania

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

Facility Name

Presbyterian Hospital

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Effects of Niacin On Fatty Acid Trapping

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