Safety and Efficacy of Adaptive Deep Brain Stimulation

• ClinicalTrials.gov Identifier: NCT04681534
• Recruitment Status: Recruiting
• First Posted: December 23, 2020
• Last Update Posted: February 7, 2022
• Sponsor: Newronika
• Information provided by (Responsible Party): Newronika

Study Description

Brief Summary:

The aim of this study is to assess the safety and the potential efficacy of personalized Local Field Potential (LFP)-based adaptive Deep Brain Stimulation (aDBS), using the implantable pulse generator (IPG) of the "AlphaDBS" System, in Parkinson's Disease patients, chronically implanted in subthalamic nucleus (STN) for DBS, at the time of IPG replacement.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease	Device: AlphaDBS System	Not Applicable

Detailed Description:

The study protocol is organized in two phases: the "short-term follow-up" and the "long-term follow-up".

PD patients in need of IPG replacement will be screened for enrollment eligibility.

For the "short-term follow-up", randomized patients will undergo 2 days of experimental sessions (i.e. one per each type of stimulation mode, cDBS and aDBS), in a well-controlled environment (i.e. during hospitalization). This part of the study will collect information on safety and potential efficacy endpoints as assessed by experienced neurologists. The "short term follow-up" phase will be considered complete when the endpoint assessment has been performed for all patients.

Patients, who will not experience severe side effects and who will be deemed suitable by the neurologist, will be eligible to continue in the "long-term follow-up" phase (i.e. 1 month) in their "home" environment. The "AlphaDBS" System will deliver the stimulation in aDBS or cDBS mode, for two weeks in each mode.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 26, 2021
• Estimated Primary Completion Date: September 30, 2022
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: conventional DBS	Device: AlphaDBS System; AlphaDBS can be programmed with two different types of stimulation: conventional DBS and adaptive DBS, that automatically adjusts the energy delivered to patient using a biosignal, local field potential (LFP), in a close loop configuration.
Experimental: adaptive DBS	Device: AlphaDBS System; AlphaDBS can be programmed with two different types of stimulation: conventional DBS and adaptive DBS, that automatically adjusts the energy delivered to patient using a biosignal, local field potential (LFP), in a close loop configuration.

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of the "AlphaDBS" System, when used in cDBS and aDBS mode [ Time Frame: 1 month ]
   Occurrence of device related adverse events
2. Change in the TEED to the patient [ Time Frame: 1 month ]
   Change in the Total Electrical Energy Delivered (TEED) to the patient

Secondary Outcome Measures :

1. PD-related motor symptoms and their fluctuations [ Time Frame: 1 month ]
   Evaluation of PD-related motor symptoms using the Unified Parkinson's Disease Rating Scale - UPDRS Part III.
2. Dyskinesia [ Time Frame: 1 month ]
   Evaluation of dyskinesia and their fluctuations through repeated clinical assessments using the Unified Dyskinesia Rating Scale - UDysRS
3. Dyskinesia [ Time Frame: up to 1 month ]
   Evaluation of the performance of a wearable accelerometer in detecting dyskinesia (compared to patient reported dyskinesia in the patient diary)
4. "Time on" with and without dyskinesia [ Time Frame: 1 month ]
   Evaluation of "time on" with and without dyskinesia, assessed through Patient Diary
5. "Time off" [ Time Frame: 1 month ]
   Evaluation of "time off", assessed through Patient Diary
6. Patient controller usability [ Time Frame: 1 month ]
   Usability will be evaluated by means of a usability questionnaire
7. Usability of the system for the physician [ Time Frame: 1 month ]
   Usability will be evaluated by means of a usability questionnaire

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Costanza Conti, PhD; +39 02 84 109 381; costanza.conti@newronika.com

Locations

Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Not yet recruiting

Milan, Italy

Contact: Elena Pirola, MD

IRCCS Istituto Neurologico Carlo Besta; Not yet recruiting

Milan, Italy

Contact: Roberto Eleopra, MD

AOU Città della Salute e della Scienza di Torino; Recruiting

Turin, Italy

Contact: Michele Lanotte, MD

Poland

Copernicus Podmiot Leczniczy; Not yet recruiting

Gdańsk, Poland

Contact: Witold Libionka, MD

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy; Recruiting

Warsaw, Poland

Contact: Tomasz Mandat, MD

Sponsors and Collaborators

Newronika

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Marceglia S, Conti C, Svanidze O, Foffani G, Lozano AM, Moro E, Volkmann J, Arlotti M, Rossi L, Priori A. Double-blind cross-over pilot trial protocol to evaluate the safety and preliminary efficacy of long-term adaptive deep brain stimulation in patients with Parkinson's disease. BMJ Open. 2022 Jan 3;12(1):e049955. doi: 10.1136/bmjopen-2021-049955.

• Responsible Party: Newronika
• ClinicalTrials.gov Identifier: NCT04681534
• Other Study ID Numbers: NWK_AlphaDBS_FIM_2019
• First Posted: December 23, 2020
• Last Update Posted: February 7, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

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