Parkinson Disease
Conditions
Keywords
DBS
Brief summary
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
Detailed description
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.
Interventions
DEVICEIntracerebral Infusion of Autologous Cerebral Spinal Fluid
Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring
Sponsors
Jeff Elias, MD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women, age 30 years and older 2. Subjects with advanced PD who are scheduled for MRI-guided DBS surgery under general anesthesia 3. Subjects who are able and willing to give informed consent and able to attend clinic visits through 6 months 4. The target nucleus, GPi or STN, is visible on MRI so that it can be targeted for the study infusion and then for MRI-guided DBS
Exclusion criteria
1. DBS surgery planned in the awake condition with microelectrode recordings and clinical testing 2. Spinal pathology not amenable to lumbar puncture 3. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the basal ganglia 4. Legal incapacity or limited legal capacity as determined by the neuropsychologist 5. Are participating or have participated in another clinical trial in the last 30 days 6. Any illness that in the investigator's opinion preclude participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events That Are Related to Treatment | 6 months postoperatively | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % Change in Un-medicated UPDRS, Motor Subsection (Part III) From Baseline to 6 Months | 6 months postoperatively in comparison to baseline | 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). |
| Vd/Vi Ratio | Day of Surgery | 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. |
| Baseline Levodopa Medication Equivalents (Milligrams) | Baseline | — |
| Change in Quality of Life Assessment With PDQ-39 Questionnaire | 6 months postoperatively in comparison to baseline | 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. |
Countries
United States
Participant flow
Recruitment details
All subjects were recruited from the medical clinic.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 4 |
| Total | 4 |
Baseline characteristics
| Characteristic | Intracerebral Infusion of Autologous CSF | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 3 Participants | — |
| Age, Categorical Between 18 and 65 years | 1 Participants | — |
| Age, Continuous | 63.25 years STANDARD_DEVIATION 13.8 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 4 participants | — |
| Sex: Female, Male Female | 2 Participants | — |
| Sex: Female, Male Male | 2 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 2 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
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.
Time frame: 6 months postoperatively
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intracerebral Infusion of Autologous CSF | Number of Participants With Adverse Events That Are Related to Treatment | 2 Participants |
Secondary
Baseline Levodopa Medication Equivalents (Milligrams)
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intracerebral Infusion of Autologous CSF | Baseline Levodopa Medication Equivalents (Milligrams) | 1893.3 Levodopa medication equivalents (milligr | Standard Deviation 246.2 |
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.
Time frame: 6 months postoperatively in comparison to baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intracerebral Infusion of Autologous CSF | Change in Quality of Life Assessment With PDQ-39 Questionnaire | -17.75 score on a scale | Standard Deviation 30.8 |
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).
Time frame: 6 months postoperatively in comparison to baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intracerebral Infusion of Autologous CSF | % Change in Un-medicated UPDRS, Motor Subsection (Part III) From Baseline to 6 Months | -18.5 percentage of UPDRS change | Standard Deviation 0.35 |
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.
Time frame: Day of Surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intracerebral Infusion of Autologous CSF | Vd/Vi Ratio | 2.69 ratio | Standard Deviation 0.17 |