Pioglitazone Vs Placebo in Combination With Niacin Extended Release on Low HDL - Full Text View

Sponsors and Collaborators:	University of Pennsylvania Kos Pharmaceuticals
Information provided by:	University of Pennsylvania
ClinicalTrials.gov Identifier:	NCT00300365

Purpose

Aim 1: We will test our primary hypothesis that combining niacin extended release (niacin-ER), at a daily dosage of up to 2.0 g with pioglitazone, at a daily dosage of 45 mg will result in a 12% greater increase in HDL-C when compared to niacin-ER monotherapy over 12 weeks in non-diabetic patients with the metabolic syndrome (see Table 1).
Aim 2: In this secondary aim, we will test our hypothesis that the combination of niacin-ER and pioglitazone will significantly increase insulin sensitivity, when compared to niacin-ER alone, as measured by the frequently sampled intravenous glucose tolerance test (FSIGTT).
Aim 3: In this additional secondary aim, we will test our hypothesis that the combination of pioglitazone and niacin-ER will reduce markers of inflammation, including C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor alpha receptor type II (sTNF--R2), and resistin, and raise adiponectin when compared to niacin-ER alone.
Aim 4: In this exploratory aim, we will measure a broad spectrum of emerging cardiovascular risk factors in order to derive a richer sense of the effects of combination pioglitazone and niacin-ER in these individuals. We will collect adipose tissue level expression (mRNA & protein) relating to cholesterol transport (PPAR-, PPAR-, and PPAR-, ABCA1, ABCG1, and SR-B1), triglyceride transport/lipolysis (HM74a, HSL), adipocytokines (TNF-a, IL-6, adiponectin, leptin, acylation-stimulating protein), and glucose regulation (glut-4 and IRS-1). [assuming sufficient mRNA yield]. These findings will serve as hypothesis-generating data for future studies..

Condition	Intervention	Phase
Metabolic Syndrome	Drug: Pioglitazone +/- placebo in combination with niacin ER	Phase IV

MedlinePlus related topics: Cholesterol

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Cholest-5-en-3-ol (3beta)- Niacin Niacin hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double Blind, Placebo Controlled Trial of Pioglitazone and Niacin Extended Release in Non-Diabetic Patients With Metabolic Syndrome

Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:

HDL cholesterol

Secondary Outcome Measures:

Measures from FSIGTT, other lipid measures, inflammatory markers, mRNA of genes related to lipid metabolism, atherosclerosis, inflammation and metabolic syndrome

Estimated Enrollment:	84
Study Start Date:	November 2005

Detailed Description:

This is a two-arm, parallel, double-blind randomized prospective clinical trial. The subjects will be asked to provide informed consent, and then undergo screening for enrollment criteria at the first visit (-5 weeks). The subjects who are eligible, and provide informed consent will return for Visit 2 baseline data (-4 weeks), and then begin the unblinded niacin-ER titration. Specifically, subjects will receive a starting dose of niacin-ER of 500 mg per day, which will be increased in 500 mg increments every week up to a dose of 2000 mg per day. Subjects will need to tolerate at least 1500 mg per day of niacin-ER in order to remain in the study and be randomized. Thus subjects who are unable to tolerate the 2000 mg daily dose of niacin-ER will be taken back to 1500 mg per day for one week and then randomized. Subjects who develop prohibitive side effects at doses less than 1500 mg per day will be discontinued from the study. All subjects who are able to take the target dose of niacin-ER will continue that dose of niacin-ER and come to the GCRC to be randomized in a 1:1 fashion to either niacin-ER plus pioglitazone or niacin-ER plus matching placebo for 12 weeks. Pioglitazone will be started at 30 mg and then increased to 45 mg at week 6. This entry design is designed to minimize the differences in mean dose of niacin-ER and dropout rate between study groups.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Men and women between the ages of 18 and 75
HDL-C ≤ 40 mg/dL for Men and HDL-C < 50 mg/dl for Women*
At least two of the following criteria (a, b, c, or d) listed below:
1. Abdominal obesity (waist circumference: men 40 inches and women 35 inches)**
2. Blood pressure > 130/>85 mmHg in untreated patients OR use of any antihypertensive agent.
3. Fasting glucose > 100 mg/dL but < 126 mg/dL.
4. Fasting triglycerides > 150 mg/dL

Exclusion Criteria:

Diabetes or use of anti-hyperglycemic medication in the last 3 months (subjects with a fasting blood glucose of > 110 mg/dL will have a OGTT to rule out diabetes mellitus).
Subjects on statin therapy may be enrolled, but only if they have been on a stable dose for at least 3 months, and are not expected to require titration of statin therapy during the course of the study.
Uncontrolled hypertension (defined as systolic blood pressure > 180, diastolic blood pressure > 100).
Triglycerides > 400 mg/dL
LDL-cholesterol level > 190 mg/dl
History of chronic renal insufficiency (serum creatinine >2.0 mg/dl).
History of liver disease or abnormal LFTs (>2x upper limit normal)
Hemoglobin < 10 mg/dL
History of congestive heart failure (NYHA Class III or IV)
Women who are pregnant or lactating
History of a non-skin malignancy within the previous 5 years
Any major active rheumatologic, pulmonary, or dermatologic disease or other chronic inflammatory condition
Surgery in the last 90 days
History of HIV positive
Active alcohol or drug abuse
Active peptic ulcer disease
Gout attack within the past 6 months
Participation in an investigational drug study within 6 weeks
Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful study participation
Subjects on warfarin may be enrolled, but they will be excluded from the optional adipose biopsy.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00300365

Contacts

Contact: Rick Samaha, MD

(215) 823-6324

rick.samaha@med.va.gov

Locations

United States, Pennsylvania
University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Rick Samaha, MD 215-823-6324 rick.samaha@med.va.gov

Sponsors and Collaborators

University of Pennsylvania

Kos Pharmaceuticals

Investigators

Principal Investigator:

Rick Samaha, MD

University of Pennsylvania

More Information

Study ID Numbers:	803751, Pionir
Study First Received:	March 6, 2006
Last Updated:	May 19, 2006
ClinicalTrials.gov Identifier:	NCT00300365
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:

HDL cholesterol
Metabolic syndrome

Study placed in the following topic categories:

Nicotinic Acids
Pioglitazone
Niacin

Additional relevant MeSH terms:

Antimetabolites
Vasodilator Agents
Disease
Vitamin B Complex
Molecular Mechanisms of Pharmacological Action
Growth Substances
Antilipemic Agents
Physiological Effects of Drugs

Cardiovascular Agents
Pharmacologic Actions
Hypoglycemic Agents
Pathologic Processes
Syndrome
Therapeutic Uses
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on January 15, 2009