Investigating Adaptive Deep Brain Stimulation in Parkinson's Disease Management

A Prospective, Multi-center, Randomized, Double-blind, Cross Over, Clinical Trial to Compare the Safety and Effectiveness of Adaptive Versus Conventional Stimulation in Levodopa- Responsive Parkinson's Disease Treated With Bilateral Deep Brain Stimulation of the Subthalamic Nucleus

The goal of this prospective, multi-center, randomized, double-blind, crossover clinical trial is to evaluate the effectiveness and safety of adaptive DBS (aDBS) and conventional DBS (cDBS) delivered through the AlphaDBS system, in levodopa-responsive Parkinson's disease subjects. Data from previous studies conducted in Europe indicate that the use of the AlphaDBS system is safe and effective in both aDBS and cDBS modes. However, such studies suggest that aDBS may lead to more ON-time without troublesome dyskinesias in some patients. The study is designed to first demonstrate safety of effectiveness of cDBS, then to directly compare effectiveness of aDBS relative to cDBS. Subjects enrolled in the study will undergo multiple visits to assess the improvement of PD symptoms and will be randomized to Mode 1 for three months, followed by Mode 2. At the end of Mode 2, subjects will select their preferred mode, which will be maintained for 3 additional months. Subjects will complete patient diaries at different time points to evaluate their symptoms throughout the day.

INCLUSION CRITERIA

Subjects who meet all of the following criteria may be given consideration for inclusion in this clinical trial:

1. Is willing and capable of signing informed consent
2. Is ≥18 years old
3. Has been diagnosed with levodopa-responsive idiopathic Parkinson's disease
4. Has a Hoehn and Yahr (H&Y) scale stage of II or III when OFF medication at screening
5. Exhibits motor fluctuations and PD-related symptoms that are not adequately controlled with medication, including motor complications of recent onset (>4 months duration)
6. Has been referred for bilateral STN DBS in accordance with local practice
7. Must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team
8. Montreal Cognitive Assessment (MoCA) score of ≥ 26 at the Baseline/Screening visit (when in "MedsON" state)
9. UPDRS-III improvement by ≥30% with the levodopa challenge test as measured at approximately 90 minutes following administration of the challenge dose
10. ≥4 hours per day (waking hours) with poor motor symptoms control (time "OFF" plus time "ON" with dyskinesia) despite optimal medical therapy, as assessed by the 3-day diary (at preop baseline)
11. Subject successfully completed a test diary reaching a sufficient level of agreement (>75%) with study personnel responses and is willing and capable of completing a 3-day diary at each of the time points required per the protocol
12. If female, subjects who are not currently pregnant as determined by negative serum pregnancy test, breastfeeding, or who are post-menopausal, surgically sterile or willing to use birth control for the duration of the study (acceptable forms of birth control are: hormone therapies (oral, injected, transdermal or implanted), IUD or other barrier methods (e.g., condom, diaphragm, cervical cap, spermicide/gel) or partner is surgically sterile
13. Subject maintained a constant anti-PD medication treatment (best medical management, as duly documented) for at least 2 weeks prior to Baseline assessments
14. Subject is willing and able to attend all study-required visits, complete the study procedures and attend appropriate follow up visits

EXCLUSION CRITERIA

The subject must not meet any of the following exclusion criteria:

1. Has contraindications for DBS surgery, including any intracranial abnormality (e.g., generalized atrophy, vascular malformation, hydrocephalus, hematoma, cavernous or venous angioma, tumor or metastases, midline shift, etc.) or metallic implant (e.g., aneurysm clip, cochlear implant, etc.) or other clinically significant space-occupying lesion which in the opinion of the surgeon would impact the ability to target and place the leads or IPG

2. Is not on a stable dose of levodopa anti-Parkinson's disease medication for at least 2 weeks prior to Screening/Baseline assessments

3. Has any current major psychiatric disorder(s), such as Major Depressive Disorder, Bipolar I or II disorder, Schizophrenia, Schizoaffective Disorder, Delusional Disorder, Brief Psychotic Disorder, Obsessive-Compulsive Disorder, or any other current psychiatric condition that in the opinion of the investigator would confound the assessment of study endpoints, prevent proper data collection and/or compromise the subject's ability to participate, based on the psychiatric/psychological assessment at screening.

   (It is permitted if a subject has a diagnosis of Major Depressive Disorder with symptoms that currently are well-controlled and managed by a stable regimen of antidepressants for a minimum of 4 weeks prior to the screening visit). Includes current moderate or severe alcohol and/or substance use disorder based on the psychiatric/psychological assessment at screening.

4. A history of suicide attempt within 3 years of the screening visit or current active suicidal ideation as determined by a psychiatric/psychological evaluation

5. Any medical condition, such as cognitive impairment, dementia, seizures, congestive heart failure, unstable angina, uncontrolled diabetes, renal failure requiring dialysis, or any other severe medical condition that could interfere with study procedures, confound the assessment of study endpoints, prevent proper data collection, or that, in the opinion of the investigator, would compromise the subject's ability to participate

6. Confirmation of diagnosis of a terminal illness associated with survival <12 months

7. Needs repeated MRI scans

8. Requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT)

9. Has an electrical or electromagnetic implant (e.g., cochlear prosthesis, pacemaker, neurostimulator, etc.) or plans to obtain, an active implanted medical device (AIMD) and/or an implanted medication pump (e.g., DUOPA™ infusion pump) and/or is treated with a portable infusion pump for any indication

10. Is on anticoagulant therapy which cannot be paused for >5 days before surgery

11. A history of cranial surgery including ablation procedure or any other previous neurosurgical procedure for the treatment of PD symptoms on either side of the brain

12. Is currently participating in another clinical study (excluding any sub-study of the present trial). The sponsor will not grant waivers or protocol exceptions to any inclusion or exclusion criteria. Safety of subjects is the utmost concern and will be prioritized at every stage throughout this protocol.