Clinical trial NCT00643890: Study of AAV-GAD Gene Transfer Into the Subthalamic Nucleus for Parkinson's Disease
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: 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
Lead sponsor: Neurologix, Inc.
Sponsor class: INDUSTRY
First posted: 2008-03-26
Enrollment: 44
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Evaluate a change in UPDRS scores
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Southfield
country: United States
facility: Henry Ford Health Systems - Franklin Pointe Medical
state: Michigan
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Science Center
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
Study officials:
References:
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. doi: 10.1016/S0140-6736(07)60982-9.
citation: 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.
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 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.
citation: 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.