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

NCT ID: NCT00300365

Last Updated: 2017-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2010-08-31

Brief Summary

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).

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 General Clinical Research Center (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.

Conditions

Metabolic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Active Pioglitazone + Open-Label Niacin

Intervention: Pioglitazone, initially 30mg, then titrated to 45mg + niacin ER 2.0 g/day + aspirin 325 mg/day

Group Type: EXPERIMENTAL

Pioglitazone

Intervention Type: DRUG

Pioglitazone, initially 30 mg, then titrated to 45 mg/day

Niacin ER

Intervention Type: DRUG

Niacin ER 2.0 g/day

Aspirin

Intervention Type: DRUG

asprin 325 mg/day

Placebo +Open-Label Niacin

Intervention: Pioglitazone Placebo + 2.0 g/day Open-Label Niacin + 325 mg/day Aspirin

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Pioglitazone placebo

Niacin ER

Intervention Type: DRUG

Niacin ER 2.0 g/day

Aspirin

Intervention Type: DRUG

asprin 325 mg/day

Interventions

Pioglitazone

Pioglitazone, initially 30 mg, then titrated to 45 mg/day

Intervention Type: DRUG

Placebo

Pioglitazone placebo

Intervention Type: OTHER

Niacin ER

Niacin ER 2.0 g/day

Intervention Type: DRUG

Aspirin

asprin 325 mg/day

Intervention Type: DRUG

Other Intervention Names

Actos

Eligibility 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 an oral glucose tolerance test (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 bp > 180, diastolic BP > 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 liver function tests (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kos Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rick Samaha, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Other Identifiers

Pionir

Identifier Type: OTHER

Identifier Source: secondary_id

803751

Identifier Type: -

Identifier Source: org_study_id