Clinical trial NCT06891781: Investigating Adaptive Deep Brain Stimulation in Parkinson's Disease Management
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Parkinson Disease, Idiopathic
Keywords: Deep Brain Stimulation
Parkinson Disease
adaptive Deep Brain Stimulation
aDBS
conventional Deep Brain Stimulation
cDBS
Lead sponsor: Newronika
Sponsor class: INDUSTRY
First posted: 2025-03-24
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: It is a prospective, multi-center, randomized, double-blind, cross over clinical trial
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: INCLUSION CRITERIA

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

* Is willing and capable of signing informed consent
* Is ≥18 years old
* Has been diagnosed with levodopa-responsive idiopathic Parkinson's disease
* Has a Hoehn and Yahr (H\&Y) scale stage of II or III when OFF medication at screening
* Exhibits motor fluctuations and PD-related symptoms that are not adequately controlled with medication, including motor complications of recent onset (\>4 months duration)
* Has been referred for bilateral STN DBS in accordance with local practice
* Must be a good surgical candidate for placement of a deep brain stimulator as judged by the DBS surgical team
* Montreal Cognitive Assessment score of ≥ 26 at the screening visit (when in "medON" state)
* UPDRS-III improvement by ≥30% with the levodopa challenge test as measured at approximately 90 minutes following administration of the challenge dose
* Successfully completed a 1-day test diary reaching a sufficient level of agreement (\>75%) with study personnel responses and is willing and capable of completing a 5-day diary at each of the time points required per the protocol
* If female, the subject is not currently pregnant (as determined by negative serum pregnancy test), breastfeeding, or is 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
* Is willing to maintain a constant anti-PD medication treatment (best medical management) for at least one month prior to DBS implantation
* Is willing and able to attend all study-required visits, complete the study procedures and attend appropriate follow-up visits

EXCLUSION CRITERIA

* 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
* Is unable or unwilling to maintain a stable dose of levodopa anti-Parkinson's disease medication for 30 days prior to DBS surgery
* 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 refers also to moderate or severe alcohol and/or substance use disorder 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).
* A history of suicide attempt within 3 years of the screening visit or current active suicidal ideation as determined by a psychiatric/ psychological evaluation
* 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
* Confirmation of diagnosis of a terminal illness associated with survival \<12 months
* Needs repeated MRI scans
* Requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT)
* 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
* Is on anticoagulant therapy which cannot be paused for \>5 days before surgery
* 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
* Is currently participating in another clinical study (excluding any sub-study of the present trial).

Primary outcomes:
measure: Improvement in Good On Time (GOT)
timeFrame: After 3 months of follow up in cDBS as compared with pre-op baseline
Secondary outcomes:
measure: GOT difference between aDBS and cDBS
timeFrame: After 3 months of follow up in each mode
measure: UPDRS III score difference between aDBS and cDBS
timeFrame: After 3 months of follow up in each mode
measure: PDQ-39 score difference between aDBS and cDBS
timeFrame: After 3 months of follow up in each mode
measure: Subject Preference for aDBS vs. cDBS
timeFrame: After 3 months of follow up in each mode
measure: Comparison of Subject Preference for aDBS vs. cDBS based on PGI-I Ratings
timeFrame: After 3 months of follow up in cDBS as compared with pre-op baseline
Other outcomes:
measure: Assessment of time to symptom relief in aDBS vs cDBS
timeFrame: After 3 months of follow up in each mode
measure: Users feedback on the AlphaDBS System
timeFrame: After 3 months of follow up in each mode
measure: AlphaDBSipg functionality
timeFrame: After 3 months of follow up in each mode
measure: Resource utilization
timeFrame: From implant to the end of the study
measure: Neurophysiologic signal quality and stability
timeFrame: From implant to the end of the study
measure: Safety Objectives
timeFrame: From screening till the end of the study
measure: Fluctuations in disease symptoms
timeFrame: After 3 month of follow up in each mode
measure: Concomitant use of anti-parkinsonian medications
timeFrame: After 3 month of follow up in each mode
measure: Mentation, behavior and mood
timeFrame: After 3 month of follow up in each mode
measure: Activities of daily life (ADLs)
timeFrame: After 3 month of follow up in each mode
measure: Complications of therapy
timeFrame: After 3 month of follow up in each mode
measure: Capabilities of people with impaired mobility
timeFrame: After 3 month of follow up in each mode
measure: Cognitive impairment
timeFrame: After 3 month of follow up in each mode
measure: Freezing of Gait (FOG) severity
timeFrame: After 3 month of follow up in each mode
measure: Balance
timeFrame: After 3 month of follow up in each mode
measure: Movement of Hands and Arms
timeFrame: After 3 month of follow up in each mode
measure: Mobility
timeFrame: After 3 month of follow up in each mode
measure: Quality of life assessment
timeFrame: After 3 month of follow up in each mode
measure: Health related quality of life assessment
timeFrame: After 3 month of follow up in each mode
measure: Non-motor symptoms associated with Parkinson's disease
timeFrame: After 3 month of follow up in each mode
measure: Clinician Global Impression
timeFrame: After 3 month of follow up in each mode
Locations:
Study officials:
References: