Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia - Full Text View

Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia

This study has been completed.

Sponsors and Collaborators:	National Center for Research Resources (NCRR) University of Pennsylvania
Information provided by:	Office of Rare Diseases (ORD)
ClinicalTrials.gov Identifier:	NCT00004809

Purpose

OBJECTIVES:

I. Develop an approach for treating patients with homozygous familial hypercholesterolemia using gene therapy with autologous hepatocytes transduced with a normal low-density lipoprotein receptor gene.

Condition	Intervention	Phase
Familial Hypercholesterolemia	Procedure: gene therapy	Phase I

Genetics Home Reference related topics:

cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency mitochondrial trifunctional protein deficiency primary carnitine deficiency

MedlinePlus related topics:

Cholesterol

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment

Further study details as provided by Office of Rare Diseases (ORD):

Estimated Enrollment:	5
Study Start Date:	June 1992

Detailed Description:

PROTOCOL OUTLINE: Autologous hepatocytes are obtained from a partial hepatectomy and transduced with a recombinant retroviral vector containing the low-density lipoprotein receptor gene. The transduced hepatocytes are infused via the inferior mesenteric vein 3 days following surgery.

Traditional therapy is discontinued for 4 weeks prior to protocol therapy and may resume 6 weeks after the hepatocyte infusion.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics-- Homozygous familial hypercholesterolemia, i.e.: Low-density lipoprotein (LDL) cholesterol greater than 500 mg/dL Autosomal dominant inheritance Early-onset tendon and tuberous xanthomas LDL receptor negative, i.e.: Receptor binding in cultured fibroblasts no more than 20% of normal OR Genotype with 2 previously described, disease-causing alleles Advanced coronary heart disease with relatively poor prognosis, i.e: Angina pectoris History of myocardial infarction Positive exercise tolerance test Atherosclerotic disease in proximal aorta or coronary arteries by ultrasound or angiogram None of the following: Unstable angina pectoris Left ventricular ejection fraction less than 30% Decompensated congestive heart failure Untreated ventricular tachycardia Moderate to severe aortic stenosis Other dyslipidemia Obstructive hepatobiliary disease

Prior/Concurrent Therapy At least 2 weeks since the following: Drugs affecting cholesterol metabolism Plasma exchange LDL apheresis --Patient Characteristics-- Age: Any age Renal: No azotemia No significant proteinuria Other: No hypothyroidism No diabetes

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004809

Sponsors and Collaborators

National Center for Research Resources (NCRR)

University of Pennsylvania

Investigators


Study Chair:	James M. Wilson	University of Pennsylvania

More Information

Study ID Numbers:	199/12011, UPHS-28040
First Received:	February 24, 2000
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00004809
Health Authority:	United States: Federal Government

Keywords provided by Office of Rare Diseases (ORD):

familial hypercholesterolemia

inborn errors of metabolism

rare disease

Study placed in the following topic categories:

Lipid Metabolism, Inborn Errors

Hypercholesterolemia, autosomal dominant

Hyperlipidemias

Metabolic Diseases

Hyperlipoproteinemia Type II

Rare Diseases

Metabolism, Inborn Errors

Genetic Diseases, Inborn

Metabolic disorder

Hypercholesterolemia

Hyperlipoproteinemias

Dyslipidemias

Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on December 03, 2008