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

• ClinicalTrials.gov Identifier: NCT00643890
• Recruitment Status: Terminated
• First Posted: March 26, 2008
• Last Update Posted: February 22, 2012
• Sponsor: Neurologix, Inc.
• Information provided by (Responsible Party): Neurologix, Inc.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Genetic: Bilateral surgical infusion of AAV-GAD into the subthalamic nucleus	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 44 participants
• Allocation: Randomized
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 2 Safety and Efficacy Study Evaluating Glutamic Acid Decarboxylase Gene Transfer to Subthalamic Nuclei in Subjects With Advanced Parkinson's Disease
• Study Start Date: August 2008
• Actual Primary Completion Date: December 2010

Arms and Interventions

Intervention Details:

• 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.

Outcome Measures

Primary Outcome Measures :

1. Evaluate a change in UPDRS scores

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305-5401

United States, Colorado

University of Colorado

Aurora, Colorado, United States, 80045

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

Henry Ford Health Systems - Franklin Pointe Medical

Southfield, Michigan, United States, 48034

United States, New York

University of Rochester

Rochester, New York, United States, 14642

United States, North Carolina

Wake Forest University Health Science Center

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

The Ohio State University

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Neurologix, Inc.

More Information

Publications of Results:

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 therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial. Lancet Neurol. 2011 Apr;10(4):309-19. doi: 10.1016/S1474-4422(11)70039-4.

Other Publications:

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. doi: 10.1016/S0140-6736(07)60982-9.

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. doi: 10.1073/pnas.0706006104. Epub 2007 Nov 27.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Niethammer M, Tang CC, LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Sapan CV, Eidelberg D, During MJ, Kaplitt MG, Feigin A. Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease. JCI Insight. 2017 Apr 6;2(7):e90133. doi: 10.1172/jci.insight.90133.

• Responsible Party: Neurologix, Inc.
• ClinicalTrials.gov Identifier: NCT00643890
• Other Study ID Numbers: NRGX-GAD-02
• First Posted: March 26, 2008
• Last Update Posted: February 22, 2012
• Last Verified: February 2012

Keywords provided by Neurologix, Inc.:

Keywords: Parkinson's disease; Gene transfer; Gene therapy; Subthalamic nucleus; Adeno-associated virus; Study placed in the following topic categories: Ganglion Cysts; Movement Disorders; Parkinson Disease; Basal Ganglia Diseases; Central Nervous System Diseases; Parkinsonian Disorders; Neurodegenerative Diseases; Brain Diseases; Additional relevant MeSH terms: Nervous System Diseases

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases