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

NCT05262348 | Withdrawn

• 1 other identifier: NWK_AlphaDBS_PIV_2022
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Parkinson Disease

Keywords

Deep Brain Stimulation

Outcome Measures

Primary Outcomes (2)

• To assess Treatment-Emergent Adverse Events

  To identify Treatment-Emergent Adverse Events (TEAEs) (including serious, device-related, stimulation-related, and/or procedure related TEAEs), discontinuations of aDBS and study discontinuation and physical or neurological findings as categorized by the Data and Safety Monitoring Board.

  9 months

• To compare change in Good on time (GOT) when the patient receives aDBS versus change in GOT when the patient receives cDBS.

  The expected treatment effectiveness of AlphaDBS IPG System with aDBS mode (∆GOTaDBS = GOTaDBS@3-Months - GOT@Baseline) and with cDBS mode (∆GOTcDBS = GOTcDBS@3-Months - GOT@Baseline) will not differ more than two hours.

  9 months

Secondary Outcomes (5)

• Success rate, number of patients with at least 2 hours improvement in each treatment mode

  9 months

• Patient fluctuations

  9 months and 36 months

• UPDRS III

  9 months and 36 months

• UdysRS

  9 months and 36 months

• Percentage of time in which the system is used in aDBS mode

  28 months

Study Arms (2)

Phase 1a - conventional stimulation

ACTIVE COMPARATOR

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

Device: conventional DBS delivered through AlphaDBS IPG System

Phase 1b - adaptive stimulation

EXPERIMENTAL

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.

Device: adaptive DBS delivered through AlphaDBS IPG System

Interventions

adaptive DBS delivered through AlphaDBS IPG System 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.

Also known as: aDBS

Phase 1b - adaptive stimulation

conventional DBS delivered through AlphaDBS IPG System DEVICE

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

Also known as: cDBS

Phase 1a - conventional stimulation

Eligibility Criteria

• Age: 55 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is ≥55 years old
• Patient has been diagnosed with levodopa-responsive idiopathic Parkinson's disease for ≥5 years
• The disease stage is II, III or IV according to the Hoehn and Yahr scale
• Patient has history of improvement of Parkinson's symptoms as a direct result of administering levodopa
• PD-related symptoms are not adequately controlled with medication, including motor complications of recent onset (\>4 months duration)
• Patient experiences persistent disabling PD-related symptoms or drug side effects (e.g., dyskinesia, motor fluctuations, or disabling "off periods") despite optimal medical therapy
• Patient has been selected for bilateral STN or Gpi DBS, independently from this study, in accordance with local standard of care DBS screening
• 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
• Patient has DBS circuit integrity assessed and confirmed by impedance testing, before IPG implantation
• ≥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
• Montreal Cognitive Assessment (MoCA) \>26 in MedON condition
• Beck Depression Inventory II (BDI-II) score \<17 in MedON condition
• UPDRS-III improvement by ≥33% following intake of anti-parkinsonian medications
• Patient is able to understand the study requirements and the treatment procedures and has provided written informed consent to participate
• Patient is willing and capable of completing a 3-day diary and reaches a sufficient level of agreement (\> 75%) with study personnel responses

You may not qualify if:

• 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.)
• 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)
• 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
• Patient has any medical condition that could interfere with study procedures, confound the assessment of study endpoints, or prevent a proper data collection
• Patient had confirmation of diagnosis of a terminal illness associated with survival \<12 months
• Patient needs repeated MRI scans
• Patient requires diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT)
• Patient carries an electrical or electromagnetic implant (e.g., cochlear prosthesis, pacemaker, neurostimulator, etc.)
• 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
• Patient is on anticoagulant therapy which cannot be paused for \>5 days before IPG implant surgery
• 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
• Patient is currently participating in another clinical study (excluding any sub-study of the present study)
• Patient is a female who is breastfeeding or of child-bearing potential with a positive urine pregnancy test or not using adequate contraception.

Sponsors & Collaborators

• Newronika: lead

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2022
• First Posted: March 2, 2022
• Study Start: August 1, 2022
• Primary Completion: August 30, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: August 12, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share