An Open-label Clinical Trial to Compare the Safety and Effectiveness of Adaptive Versus Conventional Deep Brain Stimulation

NCT ID: NCT05262348

Last Updated: 2024-08-12

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-31
• Study Completion Date: 2026-12-31

Brief Summary

The clinical trial aims to evaluate the safety and effectiveness of bilateral subthalamic nucleus (STN) and Globus Pallidus internus (GPi) deep brain stimulation (DBS) with the AlphaDBS IPG System when programmed in adaptive versus conventional stimulating modes. It includes an initial open-label, crossover phase and a long term follow-up phase, during which the patient is free to switch between stimulating modes.

Detailed Description

This is an international multi-center (North America and Europe) clinical trial to evaluate the safety and effectiveness of bilateral STN and GPi DBS with the AlphaDBS IPG System when programmed in adaptive (aDBS) versus conventional (cDBS) stimulating modes, in patients with advanced levodopa-responsive Parkinson's disease (PD).

The protocol is comprised of:

Phase 1: Initial Treatment Period: Cross-Over Design

• Phase 1a: All patients will start the study in cDBS mode. After a 1-month post-surgical stabilization, the AlphaDBS IPG System will be turned ON in cDBS mode. Participants will complete a 1-month period of programming optimization (to fine tune medical therapies and stimulation parameters) followed by a 3-month period of cDBS.
• Phase 1b: At the end of the 3-month follow up in cDBS, participants will be switched to the aDBS mode. Participants will then complete a 1-month period of optimization (to fine tune medical therapies and stimulation parameters) followed by a 3-month period of aDBS.

Phase 2: Long-term follow-up: Naturalistic Follow-up Design Patients completing Phase 1 are eligible to enter long-term follow-up for up to an additional 28 months. During this time, patients are free to change the DBS mode as preferred (with a maximum switches set by the physician). Visits at 6-month follow-ups will collect safety and efficacy data.

Conditions

Parkinson Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1a - conventional stimulation

Stimulation will be delivered bilaterally to the STN or the GPi. The stimulation parameters will be based upon standard practice by the neurologist.

Group Type: ACTIVE_COMPARATOR

conventional DBS delivered through AlphaDBS IPG System

Intervention Type: DEVICE

The AlphaDBS IPG System delivers both conventional DBS and adaptive DBS. Conventional DBS is programmed by DBS specialists.

Phase 1b - adaptive stimulation

Stimulation will be delivered bilaterally to the STN or the GPi, with the neurologist-set therapeutic window (which corresponds to the upper and lower limits for aDBS amplitude). The stimulation will be automatically adapted according to the personalized algorithm based on real time LFP analysis.

Group Type: EXPERIMENTAL

adaptive DBS delivered through AlphaDBS IPG System

Intervention Type: DEVICE

The AlphaDBS IPG System delivers both conventional DBS and adaptive DBS. Adaptive DBS is a programming mode that provides stimulation in a closed-loop adaptive "real-time" fashion, using a biosignal recorded from the same macro-electrodes routinely implanted for DBS as an input variable.

Interventions

adaptive DBS delivered through AlphaDBS IPG System

The AlphaDBS IPG System delivers both conventional DBS and adaptive DBS. Adaptive DBS is a programming mode that provides stimulation in a closed-loop adaptive "real-time" fashion, using a biosignal recorded from the same macro-electrodes routinely implanted for DBS as an input variable.

Intervention Type: DEVICE

conventional DBS delivered through AlphaDBS IPG System

The AlphaDBS IPG System delivers both conventional DBS and adaptive DBS. Conventional DBS is programmed by DBS specialists.

Intervention Type: DEVICE

Other Intervention Names

aDBS; cDBS

Eligibility Criteria

Inclusion Criteria

1. Patient is ≥55 years old

2. Patient has been diagnosed with levodopa-responsive idiopathic Parkinson's disease for ≥5 years

3. The disease stage is II, III or IV according to the Hoehn and Yahr scale

4. Patient has history of improvement of Parkinson's symptoms as a direct result of administering levodopa

5. PD-related symptoms are not adequately controlled with medication, including motor complications of recent onset (>4 months duration)

6. Patient experiences persistent disabling PD-related symptoms or drug side effects (e.g., dyskinesia, motor fluctuations, or disabling "off periods") despite optimal medical therapy

7. Patient has been selected for bilateral STN or Gpi DBS, independently from this study, in accordance with local standard of care DBS screening

8. Patient has been selected to receive Medtronic leads model 3389 or 37086, independently from this study, in accordance with local standard of care DBS screening

9. Patient has DBS circuit integrity assessed and confirmed by impedance testing, before IPG implantation

10. ≥6 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

11. Montreal Cognitive Assessment (MoCA) >26 in MedON condition

12. Beck Depression Inventory II (BDI-II) score <17 in MedON condition

13. UPDRS-III improvement by ≥33% following intake of anti-parkinsonian medications

14. Patient is able to understand the study requirements and the treatment procedures and has provided written informed consent to participate

15. Patient is willing and capable of completing a 3-day diary and reaches a sufficient level of agreement (> 75%) with study personnel responses

16. Patient has a responsible caregiver who will help completing the 3-day diary, provide feedback on activities of daily living (ADL), and ensure the patient complies with visit schedule

17. Patient is willing to maintain a constant anti-PD medication treatment (best medical management) for at least one month prior to study enrollment

18. Patient is willing and able to attend all study-required visits, complete the study procedures and attend appropriate follow up visits

Exclusion Criteria

1. Patient 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.)

2. Patient has a history of suicide attempt or current active suicidal ideation as determined by a positive response to Item 2-5 of suicide ideation sub-scale of the Columbia Suicide Severity Rating Scale (CSSR-S)

3. Patient has dementia, major depression, seizures, congestive heart failure, uncontrolled diabetes, dialysis, substance use disorders as described in DSM-V, or any other severe medical condition

4. Patient has any medical condition that could interfere with study procedures, confound the assessment of study endpoints, or prevent a proper data collection

5. Patient had confirmation of diagnosis of a terminal illness associated with survival <12 months

6. Patient needs repeated MRI scans

7. Patient requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT)

8. Patient carries an electrical or electromagnetic implant (e.g., cochlear prosthesis, pacemaker, neurostimulator, etc.)

9. Patient has, or plans to obtain, an implanted electrical stimulation medical device and/or an implanted medication pump (e.g., DUOPATM infusion pump) and/or is treated with a portable infusion pump

10. Patient is on anticoagulant therapy which cannot be paused for >5 days before IPG implant surgery

11. Patient with 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. Patient is currently participating in another clinical study (excluding any sub-study of the present study)

13. Patient is a female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 95 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Newronika

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

NWK_AlphaDBS_PIV_2022

Identifier Type: -

Identifier Source: org_study_id