Ignite Creation Date:
2025-12-26 @ 10:33 AM
Ignite Modification Date:
2025-12-31 @ 7:21 PM
Study NCT ID:
NCT00921128
Status:
WITHDRAWN
Last Update Posted:
2017-10-06
First Post:
2009-06-13
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Convection-Enhanced Delivery to Study the Pathophysiology Underlying the Clinical Features of Parkinson s Disease
Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)
Organization:
Study Overview
Official Title:
Convection Enhanced Delivery of Muscimol to Study the Pathophysiology Underlying the Clinical Features of Parkinson's Disease
Status:
WITHDRAWN
Status Verified Date:
2016-09-01
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:
* Parkinson s disease (PD) is a progressive neurodegenerative disorder that affects the brain cells that make the chemical dopamine. The primary medical treatment for PD has been to use medications to replace the dopamine that is missing from the brain. These medications can be effective at first, but after many years side effects and tolerance develop.
* Surgery can treat basic PD symptoms and complications. Deep brain stimulation (DBS) offers a safer alternative as the therapy can be adjusted and reversed to minimize side effects and optimize beneficial effects. DBS treats the symptoms of PD but does not alter its course.
* Infusions of neurochemicals or medications are another PD treatment method. NIH researchers have developed the technique of convection-enhanced delivery, which very precisely and consistently delivers infusions of many types into the brain. This project will allow researchers to infuse a medication, Muscimol, into the subthalamic region of the brain to see if it is as safe and effective as DBS.
Objectives:
* To determine whether an infusion of Muscimol into the brain is safe and relieves the symptoms of Parkinson s disease.
* To demonstrate that the infusion can be monitored with magnetic resonance imaging (MRI) using gadolinium.
Eligibility:
* Patients 18 years of age and older who have Parkinson s disease and are preparing for bilateral subthalamic nucleus (STN) DBS surgery.
* Patients will be divided into two groups. One group of patients will have a partial infusion of Muscimol into the STN, and the second group of patients will have complete infusion of Muscimol into the STN.
Design:
* This study will begin 5 days before the patient undergoes bilateral subthalamic DBS surgery.
* On Day 1 of the study, small thin tubes (microcatheters) will be inserted into the STN through the same incision and burr holes that are used for DBS. Two infusion studies of Muscimol will be performed on successive days: the first without PD medication (Day 3 of study) and the second with PD medication (Day 4 of study).
* Each infusion will be monitored in the MRI suite, and researchers will perform clinical examinations of patients PD symptoms.
* Following the study experiments, a second surgery will be performed to remove the microcatheters and to place DBS electrodes in the standard fashion.
* Parkinson s disease (PD) is a progressive neurodegenerative disorder that affects the brain cells that make the chemical dopamine. The primary medical treatment for PD has been to use medications to replace the dopamine that is missing from the brain. These medications can be effective at first, but after many years side effects and tolerance develop.
* Surgery can treat basic PD symptoms and complications. Deep brain stimulation (DBS) offers a safer alternative as the therapy can be adjusted and reversed to minimize side effects and optimize beneficial effects. DBS treats the symptoms of PD but does not alter its course.
* Infusions of neurochemicals or medications are another PD treatment method. NIH researchers have developed the technique of convection-enhanced delivery, which very precisely and consistently delivers infusions of many types into the brain. This project will allow researchers to infuse a medication, Muscimol, into the subthalamic region of the brain to see if it is as safe and effective as DBS.
Objectives:
* To determine whether an infusion of Muscimol into the brain is safe and relieves the symptoms of Parkinson s disease.
* To demonstrate that the infusion can be monitored with magnetic resonance imaging (MRI) using gadolinium.
Eligibility:
* Patients 18 years of age and older who have Parkinson s disease and are preparing for bilateral subthalamic nucleus (STN) DBS surgery.
* Patients will be divided into two groups. One group of patients will have a partial infusion of Muscimol into the STN, and the second group of patients will have complete infusion of Muscimol into the STN.
Design:
* This study will begin 5 days before the patient undergoes bilateral subthalamic DBS surgery.
* On Day 1 of the study, small thin tubes (microcatheters) will be inserted into the STN through the same incision and burr holes that are used for DBS. Two infusion studies of Muscimol will be performed on successive days: the first without PD medication (Day 3 of study) and the second with PD medication (Day 4 of study).
* Each infusion will be monitored in the MRI suite, and researchers will perform clinical examinations of patients PD symptoms.
* Following the study experiments, a second surgery will be performed to remove the microcatheters and to place DBS electrodes in the standard fashion.
Detailed Description:
Objective: The objectives of this pilot study are to gain insight into the safety, feasibility and clinical effects of infusion of a temporary acting GABAA agonist (muscimol) by convection-enhanced delivery into the subthalamic nuclei (STN) of Parkinson s disease (PD) patients undergoing deep brain stimulation (DBS) surgery.
Study population: Eight adult male and female patients with medically-intractable PD who are preparing to undergo DBS surgery and who meet all Inclusion and Exclusion Criteria will be enrolled. Six subjects will be treated (2 may be screening failures).
Design: We propose a single center pilot study of infusion of muscimol into the bilateral STN of PD patients that will undergo DBS. Subjects will be enrolled into 1 of 2 cohorts. Both cohorts will contain 3 patients each (total of 6 patients). Patients in both cohorts will undergo pre-, intra- and post-operative PD assessments. The first cohort will undergo bilateral perfusion of half of the volume (infusion of 8 microliters)of the STN with muscimol (8.8 mM) and gadolinium-DTPA (\[1 mM\] in off and on medication states on sequential days). The second cohort will undergo bilateral perfusion of the entire of the volume (infusion of 16 microliters) of the STN with muscimol (8.8 mM) and gadolinium-DTPA (\[1 mM\] in off and on medication states on sequential days). Distribution of muscimol using a surrogate imaging tracer (gadolinium-DPTA) will be tracked using real-time MR-imaging and correlated to clinical effect. After the infusions are completed, the catheters will be removed and patients will undergo placement of bilateral STN DBS. Patients will be evaluated using standard PD rating scales to determine the effects to STN neuronal suppression and to compare the effects of muscimol pharmacologic neuronal suppression to DBS effects.
Outcome measures: To determine the distribution of muscimol in the STN and to provide an anatomic correlate for clinical effects of neuronal suppression, real-time 3D-volumetric MR-imaging will be used during infusions. To assess safety, tolerability and clinical effects of muscimol infusion, standard PD rating scales (motor subsection of the Unified PD Rating Scale, timed-up-and-go gait assessment and peg board bradykinesia testing) will be performed following infusion and correlated to real-time infusion MR-imaging studies. To compare the effects of muscimol infusion to STN DBS, the assessments obtained during infusion will be compared to the similar assessment 6 months after DBS placement.
Study population: Eight adult male and female patients with medically-intractable PD who are preparing to undergo DBS surgery and who meet all Inclusion and Exclusion Criteria will be enrolled. Six subjects will be treated (2 may be screening failures).
Design: We propose a single center pilot study of infusion of muscimol into the bilateral STN of PD patients that will undergo DBS. Subjects will be enrolled into 1 of 2 cohorts. Both cohorts will contain 3 patients each (total of 6 patients). Patients in both cohorts will undergo pre-, intra- and post-operative PD assessments. The first cohort will undergo bilateral perfusion of half of the volume (infusion of 8 microliters)of the STN with muscimol (8.8 mM) and gadolinium-DTPA (\[1 mM\] in off and on medication states on sequential days). The second cohort will undergo bilateral perfusion of the entire of the volume (infusion of 16 microliters) of the STN with muscimol (8.8 mM) and gadolinium-DTPA (\[1 mM\] in off and on medication states on sequential days). Distribution of muscimol using a surrogate imaging tracer (gadolinium-DPTA) will be tracked using real-time MR-imaging and correlated to clinical effect. After the infusions are completed, the catheters will be removed and patients will undergo placement of bilateral STN DBS. Patients will be evaluated using standard PD rating scales to determine the effects to STN neuronal suppression and to compare the effects of muscimol pharmacologic neuronal suppression to DBS effects.
Outcome measures: To determine the distribution of muscimol in the STN and to provide an anatomic correlate for clinical effects of neuronal suppression, real-time 3D-volumetric MR-imaging will be used during infusions. To assess safety, tolerability and clinical effects of muscimol infusion, standard PD rating scales (motor subsection of the Unified PD Rating Scale, timed-up-and-go gait assessment and peg board bradykinesia testing) will be performed following infusion and correlated to real-time infusion MR-imaging studies. To compare the effects of muscimol infusion to STN DBS, the assessments obtained during infusion will be compared to the similar assessment 6 months after DBS placement.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 09-N-0160 | None | None | View |