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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2006 by University of Pennsylvania.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Kos Pharmaceuticals
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00300365
First received: March 6, 2006
Last updated: May 19, 2006
Last verified: March 2006
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: A Randomized, Double Blind, Placebo Controlled Trial of Pioglitazone and Niacin Extended Release in Non-Diabetic Patients With Metabolic Syndrome

Resource links provided by NLM:


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:

  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

No publications provided

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

Keywords provided by University of Pennsylvania:
HDL cholesterol
Metabolic syndrome

Additional relevant MeSH terms:
Niacin
Metabolic Syndrome X
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disease
Pathologic Processes
Pioglitazone
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Vasodilator Agents
Cardiovascular Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hypoglycemic Agents

ClinicalTrials.gov processed this record on September 30, 2014