NCT00643890

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at P25-P50 for phase_2

Geographic Reach
1 country

7 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 24, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 26, 2008

Completed
4 months until next milestone

Study Start

First participant enrolled

August 1, 2008

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed
Last Updated

February 22, 2012

Status Verified

February 1, 2012

Enrollment Period

2.3 years

First QC Date

March 24, 2008

Last Update Submit

February 20, 2012

Conditions

Keywords

Keywords:Parkinson's diseaseGene transferGene therapySubthalamic nucleusAdeno-associated virusStudy placed in the following topic categories:Ganglion CystsMovement DisordersParkinson DiseaseBasal Ganglia DiseasesCentral Nervous System DiseasesParkinsonian DisordersNeurodegenerative DiseasesBrain DiseasesAdditional relevant MeSH terms:Nervous System Diseases

Outcome Measures

Primary Outcomes (1)

  • Evaluate a change in UPDRS scores

Interventions

One-time bilateral administration of rAAV-GAD at 1X10\^12 vector genomes in 35 uL.

Eligibility Criteria

Age30 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Stanford University

Stanford, California, 94305-5401, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Henry Ford Health Systems - Franklin Pointe Medical

Southfield, Michigan, 48034, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Wake Forest University Health Science Center

Winston-Salem, North Carolina, 27157, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (4)

  • 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.

    PMID: 17586305BACKGROUND
  • 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.

    PMID: 18042721BACKGROUND
  • 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.

  • 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.

MeSH Terms

Conditions

Parkinson DiseaseGanglion CystsMovement DisordersBasal Ganglia DiseasesCentral Nervous System DiseasesParkinsonian DisordersNeurodegenerative DiseasesBrain DiseasesNervous System Diseases

Condition Hierarchy (Ancestors)

SynucleinopathiesCystsNeoplasmsMucinosesConnective Tissue DiseasesSkin and Connective Tissue Diseases

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 24, 2008

First Posted

March 26, 2008

Study Start

August 1, 2008

Primary Completion

December 1, 2010

Last Updated

February 22, 2012

Record last verified: 2012-02

Locations