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

Familial Hypercholesterolemia Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004809
• Other study ID #: 199/12011
• Secondary ID: UPHS-28040
• Status: Completed
• Phase: Phase 1
• First received: February 24, 2000
• Last updated: June 23, 2005
• Start date: June 1992

Study information

• Verified date: December 2001
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Familial Hypercholesterolemia
• Hypercholesterolemia
• Hyperlipoproteinemia Type II

Intervention

Procedure:
• gene therapy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Center for Research Resources (NCRR)	University of Pennsylvania