Ignite Creation Date:
2024-05-06 @ 12:38 AM
Last Modification Date:
2024-10-26 @ 10:52 AM
Study NCT ID:
NCT01621581
Status:
COMPLETED
Last Update Posted:
2024-07-12
First Post:
2012-06-14
Brief Title:
AAV2-GDNF for Advanced Parkinson s Disease
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Phase 1 Open-Label Dose Escalation Safety Study of Convection Enhanced Delivery CED of Adeno-Associated Virus Encoding Glial Cell Line-Derived Neurotrophic Factor AAV2-GDNF in Subjects With Advanced Parkinsons Disease
Status:
COMPLETED
Status Verified Date:
2024-06-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
- Glial cell line-derived neurotrophic factor GDNF is a chemical that may help protect and strengthen brain cells that produce dopamine Dopamine is a chemical that affects brain function People with Parkinsons disease PD have problems producing dopamine in the brain Researchers want to see if gene transfer can help deliver GDNF into the area of the brain that is damaged by PD The gene transferred in this study called AAV2-GDNF may help produce GDNF to protect the damaged brain cells
Objectives
- To test the safety and effectiveness of AAV2-GDNF gene transfer for advanced PD
Eligibility
- Individuals at least 18 years of age who have advanced PD that is not well controlled by medications
Design
Participants will be in the study for about 5 years There will be 18 outpatient study visits and a 3-day stay in the hospital There may also be overnight stays for followup visits
Participants will be screened with a physical exam and medical history Blood samples will be collected Tests of PD symptoms and mood and memory will be given Imaging studies will be used to find the right part of the brain to infuse the gene The screening visit will take place up to 60 days before surgery
Participants will have a baseline visit about a month before the surgery For 1 week before the baseline visit participants will keep a diary on any motor problems The visit will involve movement tests given before and after taking a regular dose of levodopa
Participants will have surgery to infuse AAV2-GDNF into the brain The surgery will also include a lumbar puncture spinal tap to collect cerebrospinal fluid After surgery participants will recover in the hospital for at least 2 days
Participants will have another lumbar puncture 6 and 18 months after surgery This will be an outpatient visit
Participants will have regular followup visits after the surgery These visits will include neurological tests and movement studies Visits with a neurosurgeon will take place 1 2 and 4 weeks after surgery Additional visits will take place every 3 months for the first 3 years and then at longer intervals for up to 5 years
- Glial cell line-derived neurotrophic factor GDNF is a chemical that may help protect and strengthen brain cells that produce dopamine Dopamine is a chemical that affects brain function People with Parkinsons disease PD have problems producing dopamine in the brain Researchers want to see if gene transfer can help deliver GDNF into the area of the brain that is damaged by PD The gene transferred in this study called AAV2-GDNF may help produce GDNF to protect the damaged brain cells
Objectives
- To test the safety and effectiveness of AAV2-GDNF gene transfer for advanced PD
Eligibility
- Individuals at least 18 years of age who have advanced PD that is not well controlled by medications
Design
Participants will be in the study for about 5 years There will be 18 outpatient study visits and a 3-day stay in the hospital There may also be overnight stays for followup visits
Participants will be screened with a physical exam and medical history Blood samples will be collected Tests of PD symptoms and mood and memory will be given Imaging studies will be used to find the right part of the brain to infuse the gene The screening visit will take place up to 60 days before surgery
Participants will have a baseline visit about a month before the surgery For 1 week before the baseline visit participants will keep a diary on any motor problems The visit will involve movement tests given before and after taking a regular dose of levodopa
Participants will have surgery to infuse AAV2-GDNF into the brain The surgery will also include a lumbar puncture spinal tap to collect cerebrospinal fluid After surgery participants will recover in the hospital for at least 2 days
Participants will have another lumbar puncture 6 and 18 months after surgery This will be an outpatient visit
Participants will have regular followup visits after the surgery These visits will include neurological tests and movement studies Visits with a neurosurgeon will take place 1 2 and 4 weeks after surgery Additional visits will take place every 3 months for the first 3 years and then at longer intervals for up to 5 years
Detailed Description:
Objective
While medications can temporarily alleviate the symptoms of Parkinson s disease PD they do not influence the degenerative process Progressive loss of nigral dopaminergic DA neurons the pathological hallmark of PD results in progressive neurologic dysfunction and death Glial cell line-derived neurotrophic factor GDNF was first identified based on its ability to promote the survival of embryonic DA neurons in vitro and research has demonstrated beneficial effects of GDNF in animal models of PD Preliminary clinical trials of GDNF infusions have yielded inconclusive results Observed problems with tolerability and efficacy in these studies may have been related to the methods of delivery Recent evidence indicates that gene transfer via direct delivery of viral vectors may represent a superior approach for the treatment of PD with GDNF
Study population
Twenty-four adult male and female subjects with advanced Parkinson s disease who are candidates for surgical treatment for Parkinson s disease and who meet all Inclusion and Exclusion Criteria
Design
We propose a Phase 1 single-center open-label dose escalation safety and tolerability study of adeno-associated virus serotype 2 vector AAV2 containing human GDNF complementary DNA Bilateral catheters will be placed surgically through the skull and into the brain and the vector will be delivered by convection-enhanced delivery CED to both putamina 450 microliters per hemisphere of 24 patients with advanced PD An additional 76 subjects will be allowed for screening failures Four escalating dose levels will be evaluated in the following dose cohorts 6 patients per cohort Cohort 1 9 x 1010vg Cohort 2 3 x 1011vg Cohort 3 9 x 1011vg and Cohort 4 3 x 1012vg
Outcome measures
To assess the safety tolerability and potential clinical effects of CED of AAV2-GDNF in advanced PD patients we will use defined clinical evaluations of PD Unified Parkinson s Disease Rating Scale Modified Schwab and England Activities of Daily Living scale Hoehn and Yahr Staging Lang and Fahn Dyskinesia Rating Scale On-Off Patient Diary Quality of Life Modified Rankin Scale Adverse Event Log and neurologic examinations laboratory studies hematologic immunologic and chemistry neuropsychological testing Mattis Dementia Rating Scale Beck Depression Inventory II and Parkinson Psychosis Questionnaire and neuroimaging magnetic resonance imaging and positron emission tomography
While medications can temporarily alleviate the symptoms of Parkinson s disease PD they do not influence the degenerative process Progressive loss of nigral dopaminergic DA neurons the pathological hallmark of PD results in progressive neurologic dysfunction and death Glial cell line-derived neurotrophic factor GDNF was first identified based on its ability to promote the survival of embryonic DA neurons in vitro and research has demonstrated beneficial effects of GDNF in animal models of PD Preliminary clinical trials of GDNF infusions have yielded inconclusive results Observed problems with tolerability and efficacy in these studies may have been related to the methods of delivery Recent evidence indicates that gene transfer via direct delivery of viral vectors may represent a superior approach for the treatment of PD with GDNF
Study population
Twenty-four adult male and female subjects with advanced Parkinson s disease who are candidates for surgical treatment for Parkinson s disease and who meet all Inclusion and Exclusion Criteria
Design
We propose a Phase 1 single-center open-label dose escalation safety and tolerability study of adeno-associated virus serotype 2 vector AAV2 containing human GDNF complementary DNA Bilateral catheters will be placed surgically through the skull and into the brain and the vector will be delivered by convection-enhanced delivery CED to both putamina 450 microliters per hemisphere of 24 patients with advanced PD An additional 76 subjects will be allowed for screening failures Four escalating dose levels will be evaluated in the following dose cohorts 6 patients per cohort Cohort 1 9 x 1010vg Cohort 2 3 x 1011vg Cohort 3 9 x 1011vg and Cohort 4 3 x 1012vg
Outcome measures
To assess the safety tolerability and potential clinical effects of CED of AAV2-GDNF in advanced PD patients we will use defined clinical evaluations of PD Unified Parkinson s Disease Rating Scale Modified Schwab and England Activities of Daily Living scale Hoehn and Yahr Staging Lang and Fahn Dyskinesia Rating Scale On-Off Patient Diary Quality of Life Modified Rankin Scale Adverse Event Log and neurologic examinations laboratory studies hematologic immunologic and chemistry neuropsychological testing Mattis Dementia Rating Scale Beck Depression Inventory II and Parkinson Psychosis Questionnaire and neuroimaging magnetic resonance imaging and positron emission tomography
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 12-N-0137 | None | None | None |