Safety Study of Subthalamic Nucleus Gene Therapy for Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Phase I Study of Subthalamic GAD Gene Transfer in Medically Refractory Parkinson's Disease Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00195143
• Other study ID #: 0902-478
• Status: Completed
• Phase: Phase 1
• First received: September 15, 2005
• Last updated: March 26, 2008
• Start date: August 2003
• Est. completion date: August 2005

Study information

• Verified date: September 2005
• Source: Neurologix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Recombinant DNA Advisory Committee, Office of Biotechnology Activities, National Institutes of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety of using a modified virus to transfer a gene called GAD into a region of the brain called the subthalamic nucleus in patients with advanced Parkinson's disease. The overall goal of this approach is to ultimately normalize the flow of information in several brain regions responsible for movement, to ultimately improve function in patients with this disorder. The current study is primarily designed to evaluate the safety of this approach, but patients are also being monitored for possible signs of effectiveness as well.

Description:

This study involves treatment of patients with medically refractory Parkinson's disease (PD) with gene therapy. The patients are chosen from a population of patients who would normally be candidates for standard deep brain stimulation (DBS) surgery for PD. These patients respond to medical therapy, but develop substantially reduced responses over time, often with severe fluctuations in their condition between a functional and severely non-functional state. Some patients also develop dose-limiting side effects from medication, including involuntary movements called dyskinesias and nightmares. When there are no medical contraindications, DBS is often performed in these patients to try to quiet hyperactive brain regions such as the subthalamic nucleus (STN). In PD, the STN is overactive due to a loss of GABA inputs to this region, which normally reduces neuronal firing. In turn, the STN drives other brain regions, including the globus pallidus (GPi) and substantia nigra (SNr), which are also hyperactive and which also have reduced GABA inputs. The goal of this gene therapy trial is to introduce the gene for glutamic acid decarboxylase (GAD) into the STN using an adeno-associated virus (AAV) vector, in order to permit the STN to produce it's own GABA, as well as release GABA into the GPi and SNr targets, which also have reduced GABA inputs. This is anticipated to restore a more normal pattern of information flow from this basal ganglia circuit to the thalamus and higher cortical structures in order to reduce the motor symptoms of PD, while eliminating complications arising from inserting DBS electrodes and batteries into the human body.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 75 Years

Eligibility

Inclusion Criteria:

• Duration of disease: Greater than 5 years

• Idiopathic Parkinson's disease

• Parkinson's medication stable for 3 months

• Absence of dementia

• Hoehn and Yahr rating: 3 or greater and/or UPDRS: 30 or more in "off" state and/or Complications of l-dopa therapy limiting effective use

Exclusion Criteria:

• Poor candidate for any surgery

• Significant dementia

• Secondary parkinsonism

• Severe autonomic symptoms

• Atypical Parkinson's disease

• History of substance abuse

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Genetic:
• Surgical infusion of AAV-GAD into the subthalamic nucleus

Locations

Country	Name	City	State
United States	North Shore University Hospital	Manhasset	New York

Sponsors (3)

Lead Sponsor	Collaborator
Neurologix, Inc.	North Shore University Hospital, Weill Medical College of Cornell University

Country where clinical trial is conducted

United States, 

References & Publications (1)

Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science. 2002 Oct 11;298(5592):425-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety
Secondary	Improvement in brain metabolism measured by PET scans
Secondary	Improvement in standard clinical rating scales