ABT-335 (Choline Fenofibrate) Reverse Cholesterol Transport (RCT) Study
The objectives of the study are:
- To evaluate the effect of ABT-335 (choline fenofibrate) on several parameters of RCT (reverse cholesterol transport) in men and post-menopausal women diagnosed with dyslipidemia (i.e., low high-density lipoprotein [HDL] cholesterol levels and elevated triglyceride [TG] concentrations).
- To evaluate longitudinal changes in several parameters of RCT in subjects with low HDL.
- To obtain pilot data for power calculations for subsequent comparative study.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||ABT-335 (Choline Fenofibrate)Reverse Cholesterol Transport (RCT) Study|
- Mean Change in Calculated Low Density Lipoprotein Cholesterol [ Time Frame: baseline to 12 weeks ]Mean change in calculated LDL, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,average Day 95)
- Mean Change in Plasma Triglycerides [ Time Frame: baseline to 12 weeks ]Change in plasma triglyceride, baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95)
- Mean Change in High Density Lipoprotein Cholesterol [ Time Frame: Baseline to 12 weeks ]Mean change in plasma high density plasma lipoprotein cholesterol (HDL-C)baseline (average Day 0, 1 10) to end-of-treatment (12 weeks treatment,Day 95)
- Total Cholesterol [ Time Frame: 12 weeks ]Mean Change in total cholesterol from baseline to End-of-treatment (Day 95)
- Plasma Cholesterol Efflux [ Time Frame: 12 weeks ]Change in efflux rate from baseline to end-of-treatment. The efflux rate of cholesterol from peripheral tissues into the plasma was measured as mg/kg/hr. An IV infusion of [13C2] cholesterol mixed in 10% Intralipid® or Liposyn® and 10 % ethanol was given piggy-backed into normal saline over 24 hours. This was used to determine rate of appearance (Ra) cholesterol, measured by dilution of infused [13C2] cholesterol during the plateau phase of plasma enrichment (approximately the last 4 hours of the infusion), as well as to provide the plasma cholesterol traced into biliary sterols.
- Change in Plasma Cholesterol Ester Fractional Catabolic Rate (FCR) [ Time Frame: Baseline to 12 weeks ]Change in FCR from baseline to end-of-treatment (12 weeks)
- Percent Change in de Novo Cholesterol Synthesis [ Time Frame: Baseline to 12 weeks ]Plasma DNC was measured three times from blood draws on the 3 visits in the 10 day period following the isotope infusion at baseline and again at end-of-treatment at 12 weeks, and expressed in percent. Change from baseline to end-of-treatment expressed as percent.
- Change in Neutral Sterol Excretion [ Time Frame: baseline to 12 weeks ]The excretion rate of fecal neutral and acidic sterols was measured as mg/day, for each individual three times during the 10 day period following the isotope infusions at baseline and end-of-treatment.
- Change in Bile Acid Excretion [ Time Frame: Baseline to 12 weeks ]Change in bile acid excretion from baseline to end-of-treatment
- Neutral Sterol Endogenous Excretion [ Time Frame: 12 weeks ]Change in neutral sterol endogenous excretion from baseline to end-of-treatment
- Endogenous Bile Acid Excretion [ Time Frame: 12 weeks ]Change in endogenous bile acid excretion from baseline to end-of-treatment
|Study Start Date:||March 2008|
|Study Completion Date:||May 2009|
|Primary Completion Date:||May 2009 (Final data collection date for primary outcome measure)|
ABT-335 (choline fenofibrate)
Drug: choline fenofibrate
135 mg choline fenofibrate daily(oral, capsule)
Other Name: ABT-335
This trial assesses the effects of ABT-335 on RCT as measured by cholesterol efflux or rate of appearance of cholesterol (Ra in mg/kg/hr), cholesterol excretion (%/day), RCT efflux (mg/kg/day) and de novo cholesterol synthesis (%) during a baseline period (7 days) and during a treatment period (94 days).
The goal of using RCT to reverse atherosclerosis is to increase the rate of cholesterol export or "efflux" from the tissues and plaques. An increase in this cholesterol efflux rate should shrink arterial plaques by decreasing their static accumulation of cholesterol. While some currently marketed drugs have a positive impact on RCT by increasing the rate of cholesterol excretion from the body, no drug has yet been approved to increase the rate of cholesterol efflux from the tissues
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673881
|United States, Illinois|
|Radiant Research, 515 N State St, #2700|
|Chicago, Illinois, United States, 60610|
|Principal Investigator:||Michael H Davidson, MD,FACC||Radiant Research|