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

Parkinson Disease Clinical Trial

— ADVENT  

Official title:

A Prospective, Multi-center, Open-label, Pivotal Clinical Trial to Compare the Safety and Effectiveness of Adaptive Versus Conventional Stimulation in Advanced Levodopa-Responsive Parkinson's Disease Treated With Bilateral Deep Brain Stimulation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05262348
• Other study ID #: NWK_AlphaDBS_PIV_2022
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2022
• Source: Newronika
• Contact: Jason Jones
• Phone: 901-451-4792
• Email: jason.jones[@]newronika.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 51
• Est. completion date: December 31, 2026
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 95 Years

Eligibility

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.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Newronika

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Success rate, number of patients with at least 2 hours improvement in each treatment mode	Treatement success is defined as number of patients with >2 hours ?GOTaDBS and ?GOTcDBS	9 months
Secondary	Patient fluctuations	Number of ON/OFF transitions based on the 3-day diary	9 months and 36 months
Secondary	UPDRS III	UPDRS III score, in MedOFF-StimON and MedON-StimON conditions	9 months and 36 months
Secondary	UdysRS	Score of the Unified Dyskinesia Rating Scale (UdysRS) in MedOFF-StimON and MedON-StimON condition.	9 months and 36 months
Secondary	Percentage of time in which the system is used in aDBS mode	During the long term follow up, when the patient will be able to switch between programming modes, the patient preference will be assessed considering the percentage of time in which the system is used in aDBS.	28 months