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

Sponsored by:	Johns Hopkins University
Information provided by:	Johns Hopkins University
ClinicalTrials.gov Identifier:	NCT00311987

Purpose

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.

Condition	Intervention	Phase
Hypercholesterolemia	Drug: 3,5-Diiodothyropropionic acid (DITPA) therapy	Phase I Phase II

Genetics Home Reference related topics: hypercholesterolemia

MedlinePlus related topics: Cholesterol

Drug Information available for: 3,5-Diiodothyropropionic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment:	60
Study Start Date:	April 2006
Estimated Study Completion Date:	April 2006

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00311987

Contacts

Contact: Annabelle Rodriguez, MD

410-550-4229

arodrig@jhmi.edu

Locations

United States, Maryland
Johns Hopkins Bayview Medical Center	Recruiting
Baltimore, Maryland, United States, 21224

Sponsors and Collaborators

Johns Hopkins University

Investigators

Principal Investigator:

Annabelle Rodriguez, MD

Johns Hopkins University

More Information

No publications provided

Study ID Numbers:	NA_00001376
Study First Received:	April 5, 2006
Last Updated:	April 13, 2006
ClinicalTrials.gov Identifier:	NCT00311987 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:

Hypercholesterolemia
Thyroid hormone
Diiodothyropropionic acid
Therapy

Study placed in the following topic categories:

Metabolic Diseases
Hyperlipidemias
Hormones
Metabolic Disorder

Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Metabolic Diseases
Hyperlipidemias
Hypercholesterolemia
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 07, 2009