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

Study Overview
=================
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.

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

Conditions
-----------------
Parkinson's Disease

Intervention / Treatment
-----------------
* Genetic: Bilateral surgical infusion of AAV-GAD into the subthalamic nucleus


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: Quadruple


Arms and Interventions

| Intervention/Treatment |
| --- |
|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.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate a change in UPDRS scores |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Brain Diseases, 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, Additional relevant MeSH terms:, Nervous System Diseases