Study of 3,5-Diiodothyropropionic Acid (DITPA) in Hypercholesterolemic Patients

Stopped early · Phase 1/Phase 2

Conditions studied: Hypercholesterolemia

In brief

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.

Key facts

Study ID: NCT00311987
Run by: Johns Hopkins University
People needed: 60
Starts: 2006-04-01
Expected to finish: 2007-04-01
Last updated by the study team: 2013-04-02

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients are eligible for study entry based on the following criteria:
Males or females greater than or equal to 18 years of age
Females must not be pregnant or lactating. Females of childbearing potential and males must use a reliable means of contraception.
LDL-C level greater than the NCEP goals, as determined by patients' risk category according to NCEP ATP III criteria
Risk category for coronary heart disease and coronary heart disease equivalent with LDL goal of < 100 mg/dL
Baseline lipid criteria: LDL-C = 100 to160 mg/dL and triglyceride level = 100 to 500 mg/dL
Normal thyroid function tests (total T3, total T4, and thyroid-stimulating hormone [TSH])
Hemoglobin A1C < 8.5% on a stable oral hypoglycemic or insulin regimen
On stable lipid modification pharmacotherapy (including a statin) for at least 2 weeks prior to study entry. Patients must be on at least half of the maximal doses of statins (as assessed by the Investigator), or be intolerant to statins such that the doses are not achievable.
Able to give informed consent

You may not qualify if…

Pre-Randomization Exclusion Criteria
Patients will not be eligible for the study based on the following criteria:
History of thyroid disorders of any form within 24 weeks prior to study entry
Active liver disease and/or liver transaminases greater than 1.5 X upper limit of normal
Active myocarditis, hypertrophic cardiomyopathy, uncorrected primary valvular disease, restrictive cardiomyopathy, uncorrected congenital heart disease, or constrictive pericarditis
Myocardial infarction, unstable ischemic heart disease, stroke, or coronary revascularization procedure within 24 weeks prior to study entry
Moderate or severe symptomatic congestive heart failure (New York Heart Association class III and IV)
Drug or alcohol dependence, or other conditions which may affect study compliance
Renal insufficiency (serum creatinine > 2 mg/dL)
Subjects taking other hormonal therapies (other than oral contraceptive agents and postmenopausal hormone replacement therapy) e.g., glucocorticoids, androgens, or growth hormones
Use of thyroid supplements (levothyroxine, liothyronine, etc.) or any preparation containing thyromimetic agents within 24 weeks prior to study entry
History of coagulopathy or use of anticoagulants such as warfarin
Unstable endocrine/metabolic syndrome that may affect lipid metabolism
History of atrial or ventricular arrhythmia
Diagnosis of other non-cardiac underlying medical conditions expected to impact mortality within 24 weeks after randomization

Where it is running

Johns Hopkins Bayview Medical Center — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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