Study of 3,5-Diiodothyropropionic Acid (DITPA) in Hypercholesterolemic Patients
The natural thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are known to have a cholesterol-lowering effect. Their pharmacologic use for this purpose is limited, however, by their actions on other organs, including the heart, bone, and brain, where there can be side effects of excessive thyroid hormone action. 3,5-diiodothyropropionic acid (DITPA) is a thyroid hormone analog with relative selectivity for a form of the thyroid hormone receptor expressed in the liver, where it regulates several aspects of lipid metabolism, including the clearance of low-density lipoprotein (LDL) cholesterol.
This study is designed to determine whether DITPA is safe and effective in achieving LDL cholesterol levels that are consistent with the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines in patients who have not achieved those levels on conventional therapy, due to drug-resistant disease, drug intolerance, or both.
This is a single-center, randomized, double-blind, placebo-controlled study. Following a 4-week Pre-Randomization Phase with dietary counseling and a 2-week placebo run-in, eligible patients will be randomized (1:1:1) to receive DITPA (90 mg/day, 180 mg/day), or placebo for a total treatment duration of 12 weeks.
Sixty (60) patients will be randomized to 1 of 3 treatment groups in a 1:1:1 ratio (i.e., 20 patients per treatment group):
- DITPA at 90 mg/day (45 mg twice a day [BID] taken orally)
- DITPA at 180 mg/day (90 mg BID taken orally)
- Placebo (BID taken orally)
Those patients randomized to receive DITPA at 90 mg/day will receive 45 mg/day for the first 2 weeks, followed by 90 mg/day for 10 weeks.
Those patients randomized to receive DITPA at 180 mg/day will receive 45 mg/day for the first 2 weeks, followed by 90 mg/day for the next 2 weeks, and then 180 mg/day for 8 weeks.
|Hypercholesterolemia||Drug: 3,5-Diiodothyropropionic acid (DITPA) therapy||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||A Randomized, Double-Blind Placebo-Controlled Study of 3,5-diiodothyropropionic Acid (DITPA) in Combination With Standard Therapy to Attain NCEP ATP III Goal for LDL Cholesterol in Hypercholesterolemic Patients|
- To evaluate DITPA as a lipid modifying agent in combination with standard therapy in patients with LDL cholesterol (LDL-C) levels greater than the NCEP ATP III goals, as determined by patient's risk category, in order to achieve NCEP III LDL-C goals
- To evaluate the effect of DITPA on other lipid targets: triglyceride
- total cholesterol
- ratio of total cholesterol to high-density lipoprotein (HDL)
- ratio of LDL to HDL
- HDL cholesterol
- lipoprotein a [Lp (a)]
- apolipoprotein A-I
- apolipoprotein B100
- and LDL subfractions
- To evaluate the effect of DITPA on weight and waist circumference
- To evaluate the effect of DITPA on high sensitivity C-reactive protein (hs CRP)
- To evaluate the safety of DITPA in this patient population
|Study Start Date:||April 2006|
|Study Completion Date:||April 2007|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00311987
|United States, Maryland|
|Johns Hopkins Bayview Medical Center|
|Baltimore, Maryland, United States, 21224|
|Principal Investigator:||Annabelle Rodriguez, MD||Johns Hopkins University|