Pioglitazone Vs Placebo in Combination With Niacin Extended Release on Low HDL

Metabolic Syndrome Clinical Trial

Official title: A Randomized, Double Blind, Placebo Controlled Trial of Pioglitazone and Niacin Extended Release in Non-Diabetic Patients With Metabolic Syndrome

Status Recruiting

Clinical Trial Summary

• 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..

Clinical Trial 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. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X

• NCT number: NCT00300365
• Study type: Interventional
• Source: University of Pennsylvania
• Contact: Rick Samaha, MD
• Phone: (215) 823-6324
• Email: rick.samaha@med.va.gov
• Status: Recruiting
• Phase: Phase 4
• Start date: November 2005