Phase I Study of Adenoviral Vector Mediated Gene Transfer for Ornithine Transcarbamylase in Adults With Partial Ornithine Transcarbamylase Deficiency

OBJECTIVES:

I. Determine the safety, feasibility, and potential efficacy of intravascular adenoviral vector mediated gene transfer in the liver in adults with partial ornithine transcarbamylase deficiency.

Study Overview

• Status: Terminated
• Conditions: Ornithine Transcarbamylase Deficiency Disease
• Intervention / Treatment: Genetic: Adenoviral Vector-Mediated Gene Transfer

Detailed Description

PROTOCOL OUTLINE: This is a dose escalation study. Patients undergo a femoral arterial placement of a hepatic intraarterial catheter. Patients then receive adenoviral vector mediated gene transfer intravascularly over 30 minutes.

Cohorts of 3 patients each receive escalating doses of adenoviral vector until the maximum tolerated dose is determined.

Patients are followed at 3, 5, 7, 8, 15, and 29 days, at 2 months, and then every 3 months thereafter.

Completion date provided represents the completion date of the grant per OOPD records

• Study Type: Interventional
• Enrollment: 21
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Diagnosis of partial ornithine transcarbamylase deficiency Female heterozygote with abnormal allopurinol challenge or underlying defect in either N15 urea or N15 glutamine OR Male with childhood/adulthood onset OR Family history of 2 affected children
• Stable for at least 1 month prior to study
• Plasma ammonium levels less than 50 micromoles

--Prior/Concurrent Therapy--

• Concurrent alternate pathway therapy to control hyperammonemia allowed

--Patient Characteristics--

• Hepatic: No history of liver disease
• Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No high level of neutralizing antibodies to the adenovirus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Study Chair: Steven E. Raper, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: July 1, 1998
• Study Completion: September 1, 2000

Study Registration Dates

• First Submitted: October 18, 1999
• First Submitted That Met QC Criteria: October 18, 1999
• First Posted (Estimate): October 19, 1999

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: February 1, 2000

More Information

Terms related to this study

• Keywords: rare disease; genetic diseases and dysmorphic syndromes; inborn errors of metabolism; urea cycle disorder; ornithine transcarbamylase deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Malnutrition; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Urea Cycle Disorders, Inborn; Ornithine Carbamoyltransferase Deficiency Disease; Deficiency Diseases
• Other Study ID Numbers: 199/14290; UPSM-FDR001529