Parkinson's DiseasePhase 1NCT00195143
Safety Study of Subthalamic Nucleus Gene Therapy for Parkinson's Disease
A Phase 1 study testing Surgical infusion of AAV-GAD into the subthalamic nucleus in people with Parkinson's Disease, run by Neurologix, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety of using a modified virus to transfer a gene called GAD into a region of the brain called the subthalamic nucleus in patients with advanced Parkinson's disease. Read more about this study
- Who is it for?
- Ages 25 to 75 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Surgical infusion of AAV-GAD into the subthalamic nucleus
- Type of treatment
- Injection or infusion
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2003to Aug 2005
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Duration of disease: Greater than 5 years
- Idiopathic Parkinson's disease
- Parkinson's medication stable for 3 months
- Absence of dementia
- Hoehn and Yahr rating: 3 or greater and/or UPDRS: 30 or more in "off" state and/or Complications of l-dopa therapy limiting effective use
Who cannot join
- Poor candidate for any surgery
- Significant dementia
- Secondary parkinsonism
- Severe autonomic symptoms
- Atypical Parkinson's disease
- History of substance abuse
Trial locations and contacts
1 site in 1 country.
United States1 site
North Shore University Hospital
Manhasset, New York, 11030
About this study
Official title: Phase I Study of Subthalamic GAD Gene Transfer in Medically Refractory Parkinson's Disease Patients
The purpose of this study is to determine the safety of using a modified virus to transfer a gene called GAD into a region of the brain called the subthalamic nucleus in patients with advanced Parkinson's disease. The overall goal of this approach is to ultimately normalize the flow of information in several brain regions responsible for movement, to ultimately improve function in patients with this disorder. The current study is primarily designed to evaluate the safety of this approach, but patients are also being monitored for possible signs of effectiveness as well.
Read the detailed description
This study involves treatment of patients with medically refractory Parkinson's disease (PD) with gene therapy. The patients are chosen from a population of patients who would normally be candidates for standard deep brain stimulation (DBS) surgery for PD. These patients respond to medical therapy, but develop substantially reduced responses over time, often with severe fluctuations in their condition between a functional and severely non-functional state. Some patients also develop dose-limiting side effects from medication, including involuntary movements called dyskinesias and nightmares. When there are no medical contraindications, DBS is often performed in these patients to try to quiet hyperactive brain regions such as the subthalamic nucleus (STN). In PD, the STN is overactive due to a loss of GABA inputs to this region, which normally reduces neuronal firing. In turn, the STN drives other brain regions, including the globus pallidus (GPi) and substantia nigra (SNr), which are also hyperactive and which also have reduced GABA inputs. The goal of this gene therapy trial is to introduce the gene for glutamic acid decarboxylase (GAD) into the STN using an adeno-associated virus (AAV) vector, in order to permit the STN to produce it's own GABA, as well as release GABA into the GPi and SNr targets, which also have reduced GABA inputs. This is anticipated to restore a more normal pattern of information flow from this basal ganglia circuit to the thalamus and higher cortical structures in order to reduce the motor symptoms of PD, while eliminating complications arising from inserting DBS electrodes and batteries into the human body.
- Conditions
- Parkinson's Disease
- Being tested
- Surgical infusion of AAV-GAD into the subthalamic nucleus
- Keywords
- Parkinson's disease, GABA, Subthalamic nucleus, Adeno-associated virus, AAV, Gene therapy
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Surgical infusion of AAV-GAD into the subthalamic nucleusGenetic
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Secondary outcomes (2)
Improvement in brain metabolism measured by PET scans
Improvement in standard clinical rating scales
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study startAug 2003
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants
Sponsor and investigators
- Lead sponsor
- Neurologix, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Weill Medical College of Cornell University, North Shore University Hospital
- Investigators
- Michael G Kaplitt, MD PhD, Principal investigator, Weill Medical College of Cornell UniversityMatthew J During, MD, Principal investigator, Weill Medical College of Cornell University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00195143
- Sponsor's protocol ID
- 0902-478
- Status last verified
- Sep 2005
- First submitted
- 15 Sep 2005
- Last updated
- 27 Mar 2008
- Results posted
- No
Publications
Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science. 2002 Oct 11;298(5592):425-9. doi: 10.1126/science.1074549.
PubMed 12376704Kaplitt 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.
PubMed 17586305
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Subthalamic GAD Gene Transfer in Medically Refractory Parkinson's Disease Patients
- ClinicalTrials.gov ID
- NCT00195143
- Acronym / sponsor ID
- 0902-478
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, GABA, Subthalamic nucleus, Adeno-associated virus, AAV, Gene therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants
- Lead sponsor
- Neurologix, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Weill Medical College of Cornell University, North Shore University Hospital
- Study start
- Aug 2003
- Study completion
- Aug 2005
- First posted
- 19 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety of using a modified virus to transfer a gene called GAD into a region of the brain called the subthalamic nucleus in patients with advanced Parkinson's disease. The overall goal of this approach is to ultimately normalize the flow of information in several brain regions responsible for movement, to ultimately improve function in patients with this disorder. The current study is primarily designed to evaluate the safety of this approach, but patients are also being monitored for possible signs of effectiveness as well.
Detailed description
This study involves treatment of patients with medically refractory Parkinson's disease (PD) with gene therapy. The patients are chosen from a population of patients who would normally be candidates for standard deep brain stimulation (DBS) surgery for PD. These patients respond to medical therapy, but develop substantially reduced responses over time, often with severe fluctuations in their condition between a functional and severely non-functional state. Some patients also develop dose-limiting side effects from medication, including involuntary movements called dyskinesias and nightmares. When there are no medical contraindications, DBS is often performed in these patients to try to quiet hyperactive brain regions such as the subthalamic nucleus (STN). In PD, the STN is overactive due to a loss of GABA inputs to this region, which normally reduces neuronal firing. In turn, the STN drives other brain regions, including the globus pallidus (GPi) and substantia nigra (SNr), which are also hyperactive and which also have reduced GABA inputs. The goal of this gene therapy trial is to introduce the gene for glutamic acid decarboxylase (GAD) into the STN using an adeno-associated virus (AAV) vector, in order to permit the STN to produce it's own GABA, as well as release GABA into the GPi and SNr targets, which also have reduced GABA inputs. This is anticipated to restore a more normal pattern of information flow from this basal ganglia circuit to the thalamus and higher cortical structures in order to reduce the motor symptoms of PD, while eliminating complications arising from inserting DBS electrodes and batteries into the human body.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 25 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Duration of disease: Greater than 5 years
- Idiopathic Parkinson's disease
- Parkinson's medication stable for 3 months
- Absence of dementia
- Hoehn and Yahr rating: 3 or greater and/or UPDRS: 30 or more in "off" state and/or Complications of l-dopa therapy limiting effective use
Key exclusion criteria (6 listed)
- Poor candidate for any surgery
- Significant dementia
- Secondary parkinsonism
- Severe autonomic symptoms
- Atypical Parkinson's disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Surgical infusion of AAV-GAD into the subthalamic nucleus | Genetic | – |
Primary outcome
Safety
2 secondary outcomes
Improvement in brain metabolism measured by PET scans
Improvement in standard clinical rating scales
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2008.
- Background: PubMed 12376704Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ. Subthalamic GAD gene therapy in a Parkinson's disease rat model. Science. 2002 Oct 11;298(5592):425-9. doi: 10.1126/science.1074549.
- Derived from this study: PubMed 17586305Kaplitt 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael G Kaplitt, MD PhD principal investigator
Weill Medical College of Cornell University
Matthew J During, MD principal investigator
Weill Medical College of Cornell University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Surgical infusion of AAV-GAD into the subthalamic nucleus in people with Parkinson's Disease, run by Neurologix, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00195143, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2008.