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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00300365
• Other study ID #: 803751
• Secondary ID: Pionir
• Status: Recruiting
• Phase: Phase 4
• First received: March 6, 2006
• Last updated: May 19, 2006
• Start date: November 2005

Study information

• Verified date: March 2006
• Source: University of Pennsylvania
• Contact: Rick Samaha, MD
• Phone: (215) 823-6324
• Email: rick.samaha[@]med.va.gov
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

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..

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Men and women between the ages of 18 and 75

2. HDL-C = 40 mg/dL for Men and HDL-C < 50 mg/dl for Women*

3. 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:

1. 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).

2. 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.

3. Uncontrolled hypertension (defined as systolic blood pressure > 180, diastolic blood pressure > 100).

4. Triglycerides > 400 mg/dL

5. LDL-cholesterol level > 190 mg/dl

6. History of chronic renal insufficiency (serum creatinine >2.0 mg/dl).

7. History of liver disease or abnormal LFTs (>2x upper limit normal)

8. Hemoglobin < 10 mg/dL

9. History of congestive heart failure (NYHA Class III or IV)

10. Women who are pregnant or lactating

11. History of a non-skin malignancy within the previous 5 years

12. Any major active rheumatologic, pulmonary, or dermatologic disease or other chronic inflammatory condition

13. Surgery in the last 90 days

14. History of HIV positive

15. Active alcohol or drug abuse

16. Active peptic ulcer disease

17. Gout attack within the past 6 months

18. Participation in an investigational drug study within 6 weeks

19. Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject’s safety or successful study participation

20. Subjects on warfarin may be enrolled, but they will be excluded from the optional adipose biopsy.

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

Intervention

Drug:
• Pioglitazone +/- placebo in combination with niacin ER

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	Kos Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HDL cholesterol
Secondary	Measures from FSIGTT, other lipid measures, inflammatory markers, mRNA of genes related to lipid metabolism, atherosclerosis, inflammation and metabolic syndrome