Convection Enhanced Delivery of CSF in DBS for Parkinson's

Convection Enhanced Delivery of Autologous Cerebral Spinal Fluid Improves MRI Visualizations of Basal Ganglion Nuclei During Deep Brain Stimulation Surgery

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

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: Intracerebral Infusion of Autologous Cerebral Spinal Fluid

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 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.

Device: Intracerebral Infusion of Autologous Cerebral Spinal Fluid; Unilateral infusion of 0.5 ml autologous CSF before DBS electrode insertion with MRI monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Jeff Elias, MD

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 13, 2018
• Primary Completion (ACTUAL): December 18, 2018
• Study Completion (ACTUAL): December 18, 2018

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: May 25, 2018
• First Posted (ACTUAL): May 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2021
• Last Update Submitted That Met QC Criteria: March 16, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: DBS
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: IRB-HSR #20457

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes