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

Plain-language summary

This Phase 1 study by the National Center for Research Resources (NCRR) aimed to develop an approach for treating patients with homozygous familial hypercholesterolemia using gene therapy with the patient's own liver cells (autologous hepatocytes) transduced with a normal low-density lipoprotein (LDL) receptor gene. Eligible patients had homozygous familial hypercholesterolemia with LDL cholesterol above 500 mg/dL, autosomal dominant inheritance, early-onset tendon and tuberous xanthomas, and LDL receptor negative status. The trial is completed.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Completed

Sponsor

National Center for Research Resources (NCRR)

Intervention

gene therapy

Start date

6/1/1992

Related genes

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine 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