CUSTOM-DBS: Current Steering to Optimize Deep Brain Stimulation

Current Steering to Optimize Deep Brain Stimulation

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01896115

Acronym

CUSTOM-DBS

Enrollment

Registered

2013-07-11

Start date

2013-06-30

Completion date

2014-12-31

Last updated

2020-11-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Parkinson's Disease

Keywords

Stimulation, implantable pulse generator, deep brain stimulation

Brief summary

The objective of the study is to compare different deep brain stimulation (DBS) settings using the commercially approved Boston Scientific Neuromodulation Vercise system.

Detailed description

The study is a prospective, multi-center, double-blind, randomized controlled trial. This study will compare various program settings for the bilateral stimulation of the STN using the BSC implantable Vercise™ DBS System for the treatment of levodopa-responsive, moderate to severe idiopathic PD.

Interventions

DEVICEVercise DBS settings

Deep brain stimulation set at short pulse width and monopolar stimulation using current steering

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Implanted bilaterally in STN with a Vercise DBS system for Parkinson's disease for at least three months with programming optimized according to standard of care. * UPDRS subset III score of ≥30 in the in the pre-operative meds off state. * DBS must improve PD symptoms by ≥30% in the meds off state, as measured by UPDRS subset III score. * Medical and mental fitness to comply with programming visit and study related procedures. * Able to understand the study requirements and the treatment procedures and provides written informed consent before any study-specific tests or procedures are performed. * Off symptom rigidity score of ≥2 in the evaluated arm as determined by the UPDRS-III.

Exclusion criteria

* Have any significant medical condition that is likely to interfere with study procedures or likely to confound evaluation of study endpoints, including any terminal illness with survival \<12 months. * Resting and/or action tremor score of ≥3 on the evaluated side as determined by the UPDRS-III in pre-operative meds off condition.

Design outcomes

Primary

Measure	Time frame	Description
Therapeutic Window	Day 1 programming visit	The therapeutic window refers to the range of stimulus amplitudes that provide a therapeutic effect without side effects. In other words, it is the amplitude difference between the first stimulation-induced side effect threshold (e.g., eye deviation, muscle contraction, and speech) and full rigidity control threshold at 60 µs and 30 µs pulse width DBS settings.
Unified Parkinson's Disease Rating Scale III	Day 1 programming visit	The Unified Parkinson's Disease Rating Scale (UPDRS) has four sections (I-IV) that ask patients to rate aspects of their mental state including mood (I), aspects of daily activities (II), aspects of motor function (III), and complications of treatment (IV). Here, we ask subjects to rate their motor function (UPDRS III) following interventions with 30 µs and 60 µs pulse width DBS settings. The UPDRS III scale has 14 categories including speech, facial expression, tremor at rest, action tremor, rigidity, finger tapping ability, ability to open and close hands, ability to rapidly alternate hand movements, leg agility, ability to rise from a chair, posture, gait, response to postural displacement (e.g., push), and bradykinesia. Patients rate each of these categories from 0 to 4, with 0 being normal function and 4 being the worst. Categories assessing appendages are rated for both left and right sides, allowing a maximum score (worst outcome) of 108.

Secondary

Measure	Time frame	Description
Resting Tremor Severity - Single Contact vs. Steering	Day 1 programming visit	Resting tremor was measured by a motion sensor system (Kinesia System) while either using a single contact or steering current between two contacts. Stimulation was at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms).
Side Effect Thresholds - Single Contact vs. Steering	Day 1 programming visit	This endpoint determined how much current (mA) could be applied before side effects appeared when using 60 microsecond pulse widths. Values were obtained for when current was delivered through a single contact or divided between two contacts (steering).
Finger Tapping Amplitude - Single Contact vs. Steering	Day 1 programming visit	Severity of finger-tapping bradykinesia was measured by a motion sensor system (Kinesia System) when either using a single contact or steering current between two contacts. Stimulation was at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms).

Other

Measure	Time frame	Description
Resting Tremor Severity - Pulse Width and Dorsal-Ventral Steering	Day 1 programming Visit	Resting tremor was measured by a motion sensor system (Kinesia System) at 60 µs, 30 µs, and current steering settings, at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms).
Finger Tapping Amplitude - Pulse Width and Dorsal-Ventral Steering	Day 1 programming visit	Severity of finger-tapping bradykinesia was measured by a motion sensor system (Kinesia System) at 60 µs, 30 µs, and dorsal and ventral current steering settings. Stimulation was at amplitudes defined as the therapeutic threshold for rigidity. The Kinesia System was worn by patients to measure motion parameters including linear acceleration and angular velocity during different tasks, then provided an output score on a scale of 0 (no symptoms) to 4 (severe symptoms).
Dorsal-Ventral Current Steering Therapeutic Window	Day 1 programming visit	The therapeutic window refers to the range of stimulus amplitudes that provide a therapeutic effect without side effects. In other words, this measure reports the stimulus amplitude difference between the full rigidity control threshold and the first stimulation induced side effect threshold at current steering settings (current divided 50% between adjacent electrodes).

Countries

Austria, Germany, Italy, United Kingdom, United States

Participant flow

Recruitment details

All subjects in Phase 1 received all Phase 1 treatments (Short PW, Conventional PW, Dorsal Steering, and Ventral Steering), so treatments are described as milestones below. The remaining 24 patients were assessed in Phase 2 for secondary/exploratory endpoints comparing single contact stimulation vs. current steering.

Pre-assignment details

Interim analysis showed 16 patients to be a sufficient sample size for primary endpoints.

Participants by arm

Arm	Count
All Arms (Phase 1) Patients with a Vercise DBS system programmed to 30 microseconds pulse width	15
All Arms (Phase 2) Patients with a Vercise DBS system programmed to 60 microseconds pulse width	24
Total	39

Baseline characteristics

Characteristic	All Arms (Phase 1)	All Arms (Phase 2)	Total
Age, Continuous	58.9 years STANDARD_DEVIATION 7.73	54.0 years STANDARD_DEVIATION 8.43	56.5 years STANDARD_DEVIATION 8.09
Sex: Female, Male Female	2 Participants	8 Participants	10 Participants
Sex: Female, Male Male	13 Participants	16 Participants	29 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 15
serious Total, serious adverse events	0 / 15

Outcome results

Primary

Therapeutic Window

The therapeutic window refers to the range of stimulus amplitudes that provide a therapeutic effect without side effects. In other words, it is the amplitude difference between the first stimulation-induced side effect threshold (e.g., eye deviation, muscle contraction, and speech) and full rigidity control threshold at 60 µs and 30 µs pulse width DBS settings.