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	Treatment or Intervention	Phase
Familial Hypercholesterolemia	Procedure: gene therapy	Phase I

Further Study Details: 

Expected Total Enrollment:  5

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.

Genders Eligible for Study:  Both

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

Study chairs or principal investigators

James M. Wilson,  Study Chair,  University of Pennsylvania   

Study ID Numbers:  199/12011; UPHS-28040
Record last reviewed:  December 2001
Last Updated:  October 13, 2004
Record first received:  February 24, 2000
ClinicalTrials.gov Identifier:  NCT00004809
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08