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

This study has been completed.

First Received: February 24, 2000 Last Updated: June 23, 2005 History of Changes

Sponsor:	National Center for Research Resources (NCRR)
Collaborator:	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

Study Type:	Interventional
Study Design:	Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: Chanarin-Dorfman syndrome cholesteryl ester storage disease Farber lipogranulomatosis hypercholesterolemia primary carnitine deficiency

MedlinePlus related topics: Cholesterol

U.S. FDA Resources

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

No publications provided

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

Keywords provided by Office of Rare Diseases (ORD):

familial hypercholesterolemia
inborn errors of metabolism
rare disease

Additional relevant MeSH terms:

Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Hyperlipidemias
Genetic Diseases, Inborn

Hyperlipoproteinemia Type II
Hypercholesterolemia
Hyperlipoproteinemias
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on November 25, 2009