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This study will evaluate safety foremost but also the distribution and initial effectiveness of infusion-enhanced, MRI-guided DBS for patients with medication-refractory, Parkinson's disease
This is an open-label, single-arm, pilot study investigating the safety and feasibility of infusion-enhanced, MRI-guided DBS electrode placement. The investigators intend to enroll patients with Parkinson's disease and medically-refractory motor symptoms, who are already planned for MRI-guided DBS electrodes under general anesthesia. The hypothesis of the study is that a convective micro-infusion of autologous CSF will enhance the T2-weighted MRI visualization of the targeted nucleus during image-guided DBS surgery for Parkinson's disease. The investigators will record standard clinical measures of PD at baseline and 6 months following DBS surgery. The study will recruit patients at a rate of approximately one a month and will take less than two years to complete.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intracerebral Infusion of Autologous CSF | Experimental | All subjects will receive the intracerebral infusion of autologous cerebral spinal fluid (CSF) during their deep brain stimulation (DBS) surgery. The DBS surgery will be performed on the targeted nucleus either bilaterally or unilaterally, as previously determined by a multidisciplinary team of neurology, neurosurgery, and neuropsychology. During unilateral DBS surgery, the targeted nucleus will be infused using convection enhanced delivery (CED). The nondominant side will be infused during a bilateral DBS procedure. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intracerebral Infusion of Autologous Cerebral Spinal Fluid | Device | Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events That Are Related to Treatment | Safety will be determined by an evaluation of the incidence and severity of infusion-related side effects and complications from the first treatment day visit through the 6-month post-treatment time point. All AEs will be reported and categorized by investigators as definitely, probably, possibly, unlikely, or unrelated to the CSF infusion, and/or Parkinson's disease progression. Safety will be assessed by incidence and severity of AEs, including changes in physical examinations and neurological examinations, and the number of discontinuations due to AEs. | 6 months postoperatively |
| Measure | Description | Time Frame |
|---|---|---|
| % Change in Un-medicated UPDRS, Motor Subsection (Part III) From Baseline to 6 Months | The efficacy endpoint will be focused on determining the degree of change in motor symptoms as measured from the in-medicated UPDRS, motor subsection (Part III). | 6 months postoperatively in comparison to baseline |
| Vd/Vi Ratio |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William J Elias, MD | University of Virginia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Virginia | Charlottesville | Virginia | 22908 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36724759 | Derived | Moosa S, Bond AE, Wang TR, Farzad F, Asthagiri AR, Elias WJ. Stereotactic and Functional Neurosurgery Convection-Enhanced Delivery of Autologous Cerebrospinal Fluid Enhances Basal Ganglia Visualization during MRI-Guided Deep Brain Stimulation Surgery. Stereotact Funct Neurosurg. 2023;101(2):93-100. doi: 10.1159/000528738. Epub 2023 Feb 1. |
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All subjects were recruited from the medical clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Intracerebral Infusion of Autologous CSF | All subjects will receive the intracerebral infusion of autologous cerebral spinal fluid (CSF) during their deep brain stimulation (DBS) surgery. The DBS surgery will be performed on the targeted nucleus either bilaterally or unilaterally, as previously determined by a multidisciplinary team of neurology, neurosurgery, and neuropsychology. During unilateral DBS surgery, the targeted nucleus will be infused using convection enhanced delivery (CED). The nondominant side will be infused during a bilateral DBS procedure. Intracerebral Infusion of Autologous Cerebral Spinal Fluid: Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intracerebral Infusion of Autologous CSF | All subjects will receive the intracerebral infusion of autologous cerebral spinal fluid (CSF) during their deep brain stimulation (DBS) surgery. The DBS surgery will be performed on the targeted nucleus either bilaterally or unilaterally, as previously determined by a multidisciplinary team of neurology, neurosurgery, and neuropsychology. During unilateral DBS surgery, the targeted nucleus will be infused using convection enhanced delivery (CED). The nondominant side will be infused during a bilateral DBS procedure. Intracerebral Infusion of Autologous Cerebral Spinal Fluid: Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Adverse Events That Are Related to Treatment | Safety will be determined by an evaluation of the incidence and severity of infusion-related side effects and complications from the first treatment day visit through the 6-month post-treatment time point. All AEs will be reported and categorized by investigators as definitely, probably, possibly, unlikely, or unrelated to the CSF infusion, and/or Parkinson's disease progression. Safety will be assessed by incidence and severity of AEs, including changes in physical examinations and neurological examinations, and the number of discontinuations due to AEs. | Posted | Count of Participants | Participants | 6 months postoperatively |
|
AEs were recorded from the initial consent signing until the 6 month follow up visit.
At each visit patients are examined for any incidence of adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intracerebral Infusion of Autologous CSF | All subjects will receive the intracerebral infusion of autologous cerebral spinal fluid (CSF) during their deep brain stimulation (DBS) surgery. The DBS surgery will be performed on the targeted nucleus either bilaterally or unilaterally, as previously determined by a multidisciplinary team of neurology, neurosurgery, and neuropsychology. During unilateral DBS surgery, the targeted nucleus will be infused using convection enhanced delivery (CED). The nondominant side will be infused during a bilateral DBS procedure. Intracerebral Infusion of Autologous Cerebral Spinal Fluid: Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Head pain/Headache | Nervous system disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jeff Elias | University of Virginia | (434) 924-0451 | FUSbrain@virginia.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 8, 2018 | Mar 16, 2021 | Prot_SAP_003.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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The ratio of the volume of distribution (Vd) immediately following the infusion (Vi) with intraoperative 1.5T MRI, T2-weighted sequences to the volume of the infusion (Vi) will be calculated. Each volume is measured in microliters (uL). The distribution of the infusion by convective properties in a deep brain human nucleus (GPi or STN) will be determined by calculating the Vd/Vi ratio. |
| Day of Surgery |
| Baseline Levodopa Medication Equivalents (Milligrams) | Baseline |
| Change in Quality of Life Assessment With PDQ-39 Questionnaire | The PDQ-39 questionnaire includes 39 quality of life questions rated on a scale of 0-4. 0 indicating least frequent (never) and 4 indicating most frequent (always). The mean change in the sum of the PDQ-39 questionnaire is being reported with a overall score of 0 being the best quality of life and a maximum score of 156 being the worst possible quality of life. | 6 months postoperatively in comparison to baseline |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | % Change in Un-medicated UPDRS, Motor Subsection (Part III) From Baseline to 6 Months | The efficacy endpoint will be focused on determining the degree of change in motor symptoms as measured from the in-medicated UPDRS, motor subsection (Part III). | Posted | Mean | Standard Deviation | percentage of UPDRS change | 6 months postoperatively in comparison to baseline |
|
|
|
| Secondary | Vd/Vi Ratio | The ratio of the volume of distribution (Vd) immediately following the infusion (Vi) with intraoperative 1.5T MRI, T2-weighted sequences to the volume of the infusion (Vi) will be calculated. Each volume is measured in microliters (uL). The distribution of the infusion by convective properties in a deep brain human nucleus (GPi or STN) will be determined by calculating the Vd/Vi ratio. | Posted | Mean | Standard Deviation | ratio | Day of Surgery |
|
|
|
| Secondary | Baseline Levodopa Medication Equivalents (Milligrams) | Posted | Mean | Standard Deviation | Levodopa medication equivalents (milligr | Baseline |
|
|
|
| Secondary | Change in Quality of Life Assessment With PDQ-39 Questionnaire | The PDQ-39 questionnaire includes 39 quality of life questions rated on a scale of 0-4. 0 indicating least frequent (never) and 4 indicating most frequent (always). The mean change in the sum of the PDQ-39 questionnaire is being reported with a overall score of 0 being the best quality of life and a maximum score of 156 being the worst possible quality of life. | Posted | Mean | Standard Deviation | score on a scale | 6 months postoperatively in comparison to baseline |
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| 0 |
| 4 |
| 0 |
| 4 |
| 2 |
| 4 |
| Word finding difficulty | Nervous system disorders | Systematic Assessment |
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| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |