Safety and Efficacy of Adaptive Deep Brain Stimulation

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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Device: AlphaDBS System

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 Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Costanza Conti, PhD; Phone Number: +39 02 84 109 381; Email: costanza.conti@newronika.com

Study Locations

• Italy
  • Milan, Italy
    • Not yet recruiting
    • Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico
    • Contact: Elena Pirola, MD
  • Milan, Italy
    • Not yet recruiting
    • IRCCS Istituto Neurologico Carlo Besta
    • Contact: Roberto Eleopra, MD
  • Turin, Italy
    • Recruiting
    • AOU Citta della Salute e della Scienza di Torino
    • Contact: Michele Lanotte, MD
• Poland
  • Gdańsk, Poland
    • Not yet recruiting
    • COPERNICUS Podmiot Leczniczy
    • Contact: Witold Libionka, MD
  • Warsaw, Poland
    • Recruiting
    • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
    • Contact: Tomasz Mandat, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Newronika

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 26, 2021
• Primary Completion (ANTICIPATED): September 30, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: December 19, 2020
• First Posted (ACTUAL): December 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: NWK_AlphaDBS_FIM_2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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