Personalized Deep Brain Stimulation for Parkinson's Disease

A Double-blind Crossover Study to Evaluate the Safety and Efficacy of Adaptive Deep Brain Stimulation Delivered Through AlphaDBS System in Patients With Parkinson's Disease

This study is testing a new personalized brain stimulation method to see if it can better help people with Parkinson's Disease manage their symptoms compared to the standard treatment.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sex: All
• Sponsor: Newronika (Industry-sponsored)
• Locations: 8 sites (Milan and 7 other locations)
• Trial ID: NCT04681534 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of personalized adaptive Deep Brain Stimulation (aDBS) for patients with Parkinson's Disease using the AlphaDBS System. It consists of two phases: a short-term follow-up involving controlled experimental sessions to compare aDBS and conventional DBS (cDBS), and a long-term follow-up where patients will use the aDBS system at home. The study aims to gather data on the effectiveness and safety of this innovative stimulation approach in managing Parkinson's symptoms.

Who should consider this trial

Good fit: Ideal candidates include patients with idiopathic Parkinson's Disease who require an implantable pulse generator replacement and have been treated with deep brain stimulation for at least three years.

Not a fit: Patients with severe cognitive decline or major psychiatric issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective and personalized treatment options for patients with Parkinson's Disease.

How similar studies have performed: Other studies have shown promise in adaptive deep brain stimulation approaches, indicating potential for success in this novel application.

Eligibility criteria

IPG Replacement Patients:

Inclusion Criteria

1. Diagnosis of idiopathic PD;
2. Subject is bilaterally treated with DBS in the STN using a Medtronic Activa PC or Activa RC IPG (mono-channnel or dual channel);
3. DBS implant for at least 3 years and in need of battery replacement within 12 months after consent;
4. Patients must be able to understand and sign the informed consent document.

Exclusion criteria

1. Patients with severe cognitive decline, as resulting from MoCA assessment (MoCA score \< 10);
2. Patients with major psychiatric issues or any other condition that, based on the physician opinion, could interfere with the study conduct (e.g. severe depression, psychosis, etc.);
3. Patients with any medical conditions potentially interfering with DBS battery replacement surgery (e.g. severe hypertension, active cancer, intake of drugs interfering with the coagulation etc.);
4. Need to replace or reposition the leads during the IPG replacement procedure;
5. Patients with \> 10 recurrent falls experienced in the 3 months prior to consent;
6. Patients that cannot tolerate an interruption of DBS stimulation for at least 30 min;
7. Patients taking less than one levodopa dose per day;
8. Patients without suitable LFPs recordings or with significant artifacts;
9. Pregnant or breastfeeding women.

De Novo DBS Patients:

Inclusion Criteria

1. Patient is ≥ 18 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 PD-related symptoms as a direct result of levodopa intake;
5. Patient has been selected for bilateral STN or GPi DBS, independently from this study, in accordance with local standard of care DBS screening;
6. Patient has been selected to receive Medtronic leads model 3389 or 37086 or Abbott directional leads model number 6170 or 6172 or 6371, independently from this study, in accordance with local standard of care for DBS;
7. Patient has DBS-leads circuit integrity assessed and confirmed by impedance testing, before IPG implantation;
8. MoCA score \> 26 in best medical condition;
9. BDI-II score \< 17 in best medical condition;
10. UPDRS-III improvement by ≥ 33% with levodopa challenge test (at approximately 90 min from the intake of the usual morning levodopa dose plus 30%);
11. Patient is able to understand the study requirements and the treatment procedures and has provided written informed consent to participate;
12. 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;
13. Patient is on stable PD-medication for one month prior surgery;
14. 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 (C-SSRS);
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;
14. Patients without suitable LFPs recordings or with significant artifacts.

Where this trial is running

Milan and 7 other locations

• Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico — Milan, Italy (Recruiting)
• IRCCS Istituto Neurologico Carlo Besta — Milan, Italy (Completed)
• Azienda Ospedale Universitario di Padova - Università di Padova — Padova, Italy (Withdrawn)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome, Italy (Completed)
• AOU Città della Salute e della Scienza di Torino — Turin, Italy (Completed)
• Maastricht Medical Center — Maastricht, Netherlands (Withdrawn)
• Copernicus Podmiot Leczniczy — Gdansk, Poland (Withdrawn)
• Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy — Warsaw, Poland (Completed)

Study contacts

• Study coordinator: Costanza Conti, PhD

Conditions Parkinson Disease