Stimulus-Evoked Directional Field Potentials to Guide Subthalamic and Pallidal DBS for PD

Parkinson Disease Clinical Trial

Official title:

Stimulus-Evoked Directional Field Potentials to Guide Subthalamic and Pallidal DBS for PD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06169852
• Other study ID #: IRB-300011568
• Secondary ID: 1UG3NS130202-01A
• Status: Recruiting
• Phase: N/A
• Start date: January 12, 2024
• Est. completion date: January 1, 2029

Study information

• Verified date: November 2023
• Source: University of Alabama at Birmingham
• Contact: Harrison Walker, MD
• Phone: 205-934-0683
• Email: hcwalker[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine whether new deep brain stimulation (DBS) device technologies can generate and record brain rhythms to reveal the best location for clinical stimulation.

Description:

The investigator's goal is to better understand how deep brain stimulation (DBS) modifies local neuronal activity and to pioneer device technologies that can record local DBS-evoked potentials (DLEPs) to guide therapy. Together, Neuromodulation eXperiment Testbed system (NEXT) with a novel 16-contact directional lead (Argyle) are uniquely suited for these purposes. The investigator's vision is for NEXT to guide both electrode targeting during surgery and programming in clinic, eventually as an integrated component of the implanted pulse generator. The results will inform directional DBS for PD and serve as a model for translation to other diseases where knowledge on DBS circuit interactions is at an even earlier stage.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: January 1, 2029
• Est. primary completion date: January 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age >18 years and older

2. Clinically definite, advanced idiopathic PD based on at least 2 of 3 cardinal PD features

3. Disease duration of 4 years or more

4. Participant has elected to undergo awake DBS surgery as part of routine care, and the subthalamic nucleus (STN) or globus pallidus interna (GPi) are recommended by the multidisciplinary DBS committee as the surgical target.

5. Participant is healthy enough to undergo surgery and the research protocol

6. Normal, or essentially normal, preoperative brain MRI, except for expected mild abnormalities associated with advanced PD

7. Willingness and ability to cooperate during awake DBS surgery, as well as during post-operative evaluations, adjustments of medications and stimulator settings

8. Participant's health insurance and/or Medicare covers DBS surgery as part of routine care

9. Refractory motor symptoms such as tremors, dyskinesias, wearing off, and/or motor fluctuations, causing significant disability or occupational dysfunction, despite reasonable attempts at medical management, as determined by our consensus DBS committee

10. Stable doses of PD medications for at least 28 days prior to baseline assessments

11. Improvement of motor signs =30% with dopaminergic medication as assessed with the use of the Movement Disorders - Unified Parkinson's Disease Rating Scale, part III as performed at baseline visit

12. Disease severity ratings above Hoehn and Yahr stage 1, defined as unilateral involvement only with minimal or no functional disability, with scores ranging from 0 to 5 and higher scores indicating more severe disease as performed at baseline visit.

13. Score of more than 6 for activities of daily living in the worst "off" medication condition despite medical treatment, as assessed with the use of the MDS-UPDRS II, or mild-to-moderate impairment in social and occupational functioning as performed at baseline visit

14. Dementia Rating Scale-2 score of =130 on medications from routine care record review

15. Beck Depression Inventory II score of =25 on medications as performed at baseline visit

16. Participant expresses understanding of the consent process, terms of the study protocol, is available for follow-up over the length of the study, and signs informed consent

Exclusion Criteria:

1. Age <18 years

2. Participant's insurance will not cover the costs of surgery with an investigational device (Future exclusion for pending Aims 2 and 3 only)

3. Medical contraindications such as current uncontrolled hypertension, heart disease, coagulopathy, or other conditions contraindicating DBS surgery or stimulation

4. Duration of disease of <4 years

5. Diagnosis or suspicion of atypical parkinsonism or drug-induced parkinsonism, or significant neurological disease other than Parkinson's disease

6. Diagnosis of psychogenic movement disorder based on consensus criteria

7. Patient is undergoing DBS electrode placement under general anesthesia without awake electrophysiological and clinical testing during implant

8. Score of >25 on the Beck Depression Inventory II or history of suicide attempt

9. Any current acute psychosis, alcohol abuse or drug abuse

10. Clinical dementia

11. Ongoing or pervasive impulse control disorder not resolved by reduction of dopaminergic medications

12. Use of anticoagulant medications that cannot be discontinued during perioperative period

13. History of hemorrhagic stroke

14. Current or future risk of immunocompromise that might significantly increase infection risk

15. History of recurrent of unprovoked seizures

16. Lack of clear levodopa responsiveness

17. The presence of an implanted device whether turned on or off.

18. Prior DBS surgery or ablation within the affected basal ganglion

19. Prior DBS surgery on the opposite side of the brain (future pending Aims 2 and 3 only)

20. A condition requiring or likely to require the use of diathermy

21. Structural lesions such as basal ganglionic stroke, tumor, or vascular malformation as etiology of the movement disorder

22. Any medical or psychological problem that would interfere with completing the study protocol, as determined by the research team

23. A female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Neuromodulation eXperiment Testbed system (NEXT) stimulation
Initial studies in this aim will use NEXT to stimulate and record neural activity at clinically effective sites.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
University of Alabama at Birmingham	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Validate the biological origin of brain signals using the Neuromodulation eXperiment Testbed (NEXT) system during standard of care Deep Brain Stimulation surgery, both awake and under general anesthesia.	The investigator will validate the biological origin of the signals using pairs of DBS pulses and neural refractoriness with the NEXT System at therapeutically relevant stimulus amplitudes (i.e., inside and outside the therapeutic window).	At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia).
Primary	Test whether a novel 16-contact DBS lead elicits spatiotemporally distinct oscillations in subthalamic nucleus versus globus pallidus interna.	This investigators efforts will yield granular spatial maps of neural engagement across the two canonical targets for PD to guide targeting (awake or under anesthesia) and clinical programming.	At standard of care DBS surgery (awake) and approximately one week later at standard of care battery placement (under general anesthesia).
Primary	Test whether spatial maps of DBS-evoked oscillations predict clinically effective stimulation sites on the 16-contact lead.	The investigator will test whether spatial maps of DBS-evoked neural activity predict clinically effective locations for directional DBS on the 16-contact lead.	At standard of care DBS surgery (awake), approximately one week later at standard of care battery placement (under general anesthesia), at in a research clinical assessment at 6 months after DBS surgery.