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

NCT ID: NCT00643890

Last Updated: 2012-02-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Parkinson's Disease

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Interventions

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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.

Intervention Type GENETIC

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Neurologix, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Stanford University

Stanford, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Henry Ford Health Systems - Franklin Pointe Medical

Southfield, Michigan, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Wake Forest University Health Science Center

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 17586305 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18042721 (View on PubMed)

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.

Reference Type RESULT
PMID: 21419704 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28405611 (View on PubMed)

Other Identifiers

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NRGX-GAD-02

Identifier Type: -

Identifier Source: org_study_id

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