Clinical trial NCT00728910
Conditions: Dyslipidemia
Keywords: Low HDL cholesterol High triglycerides niacin fibrate
Sponsor: University of Pennsylvania
Start date: 2008-06-01; Completion date: 2009-08-01
Enrollment: 25 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The investigators propose to investigate if using a combination of medications that may improve cholesterol give additional benefit to that gained from the statin medication, Lipitor. It is recommended that patients who meet certain criteria for risk of heart disease take a statin medication to improve cholesterol and hopefully reduce risk of heart disease. The combination therapy will include Lipitor, Niaspan, and investigational medication (known as ABT335) in a class of drugs called fibrates. We are looking to see if and how these three medications together might improve risk factors for atherosclerosis and influence HDL cholesterol. The study will also look at the safety and any side effects that might be associated with this combination of medications.

Detailed description:
Objectives Summary

\* To investigate whether the progressive addition of a fibrate and niacin to baseline statin therapy will improve apolipoprotein A-I kinetics, postprandial lipidemia, and postabsorptive lipoproteins and metabolism in adult men and women with atherogenic dyslipidemia.

Major Efficacy Aims

* Objective 1 is to test the hypothesis that the fibrate ABT335 and extended release (ER) niacin progressively improve apolipoprotein A-I kinetics when added sequentially to baseline therapy with atorvastatin. The key outcomes include the apolipoprotein AI rate of catabolism and rate of production.
* Objective 2 is to test the hypothesis that the fibrate ABT335 and ER niacin progressively improve postprandial lipidemia by oral fat challenge when added sequentially to baseline therapy with atorvastatin. Key outcomes include the incremental area under the curve for triglycerides and high-density lipoprotein cholesterol.
* Objective 3 is to test the hypothesis that the fibrate ABT335 and ER niacin progressively improve markers of postabsorptive lipoproteins and metabolism when added sequentially to baseline therapy with atorvastatin. Key outcomes include a. fasting cholesterol efflux, b. HDL cholesterol, apolipoprotein A-I, and enzymes that remodel HDL, c. atherogenic lipoproteins, and d. markers of energy metabolism and e. markers of inflammation.

Additional Aims

\* Objective 4 is to assess tolerability and adverse events when ABT335 and ER niacin are added sequentially to atorvastatin. Specifically, we will assess changes in hepatobiliary laboratory tests (including incidence of elevation), incidence of symptomatic myalgia, and incidence of flushing. On an exploratory basis, we will enhance the flushing evaluation with objective and subjective measurements of flushing during inpatient visits.

Study Design:

This is an open-label feasibility study of fixed-sequence addition of lipid-altering medications, in which comparisons are made to the baseline for each subject. Subjects begin a lead-in phase in which they start the study statin (atorvastatin) or switch from previous statin therapy to the study statin. Subjects will wash off other excluded lipid-altering drugs during the lead-in. Subjects return for the first inpatient visit, where they have baseline studies on statin monotherapy. At the end of this visit, subjects are started on fibrate therapy (ABT335). They repeat the studies on dual therapy with statin and fibrate, and then add niacin (ER niacin). To minimize flushing during chronic treatment, they start aspirin 325 mg daily, or titrate to 325 mg if they are taking a lower dose of aspirin (e.g. 81 mg). Finally, they repeat the studies on triple therapy with statin, fibrate, and niacin/aspirin.

Arms: arm 1: atorvastatin 10 mg/day by mouth for a total duration of 4 weeks arm 2: ABT335 135 mg/day by mouth added to atorvastatin for a total duration of at least 8 arm 3: ER niacin titrated up to 2 g/day with aspirin 325 mg/day by mouth added to atorvastatin and ABT335 for 10 weeks
Interventions: intervention 1: Atorvastatin intervention 2: ABT335 intervention 3: ER Niacin
Intervention descriptions: intervention 1: 10 mg QD for 4 weeks intervention 2: 135 mg QD added to atorvastatin for 8 weeks intervention 3: 2000 mg QD added to atorvastatin and ABT335 for 10 weeks

Protocol documents: