Trial Outcomes & Findings for Convection Enhanced Delivery of CSF in DBS for Parkinson's (NCT NCT03540134)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

4 participants

Primary outcome timeframe

6 months postoperatively

Results posted on

2021-04-08

Participant Flow

All subjects were recruited from the medical clinic.

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	4
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
Age, Categorical <=18 years	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=4 Participants
Age, Categorical >=65 years	3 Participants n=4 Participants
Age, Continuous	63.25 years STANDARD_DEVIATION 13.8 • n=4 Participants
Sex: Female, Male Female	2 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=4 Participants
Region of Enrollment United States	4 participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
Number of Participants With Adverse Events That Are Related to Treatment	2 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
% Change in Un-medicated UPDRS, Motor Subsection (Part III) From Baseline to 6 Months	-18.5 percentage of UPDRS change Standard Deviation .35

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
Vd/Vi Ratio	2.69 ratio Standard Deviation .17

SECONDARY outcome

Timeframe: Baseline

Outcome measures

Outcome measures
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
Baseline Levodopa Medication Equivalents (Milligrams)	1893.3 Levodopa medication equivalents (milligr Standard Deviation 246.2

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intracerebral Infusion of Autologous CSF n=4 Participants 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
Change in Quality of Life Assessment With PDQ-39 Questionnaire	-17.75 score on a scale Standard Deviation 30.8

Adverse Events

Intracerebral Infusion of Autologous CSF

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intracerebral Infusion of Autologous CSF n=4 participants at risk 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
Nervous system disorders Head pain/Headache	50.0% 2/4 • 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.
Nervous system disorders Word finding difficulty	25.0% 1/4 • 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.

Additional Information

Dr. Jeff Elias

University of Virginia

Phone: (434) 924-0451

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place