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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00004809
Recruitment Status : Completed
First Posted : February 25, 2000
Last Update Posted : June 24, 2005
University of Pennsylvania
Information provided by:
Office of Rare Diseases (ORD)

Brief Summary:


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 or disease Intervention/treatment Phase
Familial Hypercholesterolemia Procedure: gene therapy Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Enrollment : 5 participants
Primary Purpose: Treatment
Study Start Date : June 1992

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


--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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00004809

Sponsors and Collaborators
National Center for Research Resources (NCRR)
University of Pennsylvania
Study Chair: James M. Wilson University of Pennsylvania Identifier: NCT00004809     History of Changes
Other Study ID Numbers: 199/12011
First Posted: February 25, 2000    Key Record Dates
Last Update Posted: June 24, 2005
Last Verified: December 2001

Keywords provided by Office of Rare Diseases (ORD):
familial hypercholesterolemia
inborn errors of metabolism
rare disease

Additional relevant MeSH terms:
Hyperlipoproteinemia Type II
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn