Study of AAV-GAD Gene Transfer Into the Subthalamic Nucleus for Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Phase 2 Safety and Efficacy Study Evaluating Glutamic Acid Decarboxylase Gene Transfer to Subthalamic Nuclei in Subjects With Advanced Parkinson's Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00643890
• Other study ID #: NRGX-GAD-02
• Status: Terminated
• Phase: Phase 2
• First received: March 24, 2008
• Last updated: February 20, 2012
• Start date: August 2008

Study information

• Verified date: February 2012
• Source: Neurologix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety and efficacy of AAV-GAD gene transfer into the subthalamic nucleus (STN) region of the brain. This study involves the treatment of subjects with medically refractory Parkinson's disease (PD). The gene transfer product, a disabled virus with a gene called GAD, will be infused into the STN bilaterally using stereotactic surgical techniques. The overall goal of this approach is to normalize the activity of the STN and reduce the motor symptoms of PD.

Because the change in UPDRS demonstrated a positive outcome, the sham surgery subjects from the blinded portion of the study will be invited to crossover into the Open-label Arm portion of the study. The Open-label Arm will further evaluate the safety and efficacy of AAV-GAD gene transfer into the subthalamic nucleus (STN) region of the brain.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Idiopathic Parkinson's disease

• Duration of disease for at least 5 years

• Levodopa responsiveness for at least 12 months

• UPDRS Part 3 score = 25 or more in "off" state

Exclusion Criteria:

• Past history of brain surgery for PD

• Beck Depression Inventory Score = 20

• Any history of cerebral insult or central nervous system infection

• Cognitive impairment score < 130 on the Mattis Dementia Rating Scale

• Focal neurological deficits

• Evidence of significant medical or psychiatric disorders

• Secondary Parkinsonism

• Atypical Parkinson's disease

• History of substance abuse

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Genetic:
• Bilateral surgical infusion of AAV-GAD into the subthalamic nucleus
One-time bilateral administration of rAAV-GAD at 1X10^12 vector genomes in 35 uL.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The Ohio State University	Columbus	Ohio
United States	University of Rochester	Rochester	New York
United States	Henry Ford Health Systems - Franklin Pointe Medical	Southfield	Michigan
United States	Stanford University	Stanford	California
United States	Wake Forest University Health Science Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Neurologix, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (3)

Feigin A, Kaplitt MG, Tang C, Lin T, Mattis P, Dhawan V, During MJ, Eidelberg D. Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's disease. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19559-64. Epub 2007 Nov 27. — View Citation

Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet. 2007 Jun 23;369(9579):2097-105. — View Citation

LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A. AAV2-GAD gene — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate a change in UPDRS scores			No