Trial Outcomes & Findings for CUSTOM-DBS: Current Steering to Optimize Deep Brain Stimulation (NCT NCT01896115)

NCT ID: NCT01896115

Last Updated: 2020-11-19

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 40 participants
• Primary outcome timeframe: Day 1 programming visit
• Results posted on: 2020-11-19

Participant Flow

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.

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

Participant milestones

Measure	All Arms (Phase 1) Patients with a Vercise DBS system programmed to 30 microseconds pulse width Patients with a Vercise DBS system programmed to 60 microseconds pulse width Patients with a Vercise DBS system programmed to steer current ventrally Patients with a Vercise DBS system programmed to steer current dorsally.	All Arms (Phase 2) Patients with a Vercise DBS system programmed to 30 microseconds pulse width Patients with a Vercise DBS system programmed to 60 microseconds pulse width Patients with a Vercise DBS system programmed to steer current Patients with a Vercise DBS system programmed to single contact stimulation
Overall Study STARTED	16	24
Overall Study Phase 1 Short PW	15	0
Overall Study Phase 1 Conventional PW	15	0
Overall Study Phase 1 Dorsal Steering	15	0
Overall Study Phase 1 Ventral Steering	15	0
Overall Study Phase 2 Single Contact	0	24
Overall Study Phase 2 Steering	0	24
Overall Study COMPLETED	15	24
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CUSTOM-DBS: Current Steering to Optimize Deep Brain Stimulation

Baseline characteristics by cohort

Measure	All Arms (Phase 1) n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	All Arms (Phase 2) n=24 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Total n=39 Participants Total of all reporting groups
Age, Continuous	58.9 years STANDARD_DEVIATION 7.73 • n=5 Participants	54.0 years STANDARD_DEVIATION 8.43 • n=7 Participants	56.5 years STANDARD_DEVIATION 8.09 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	8 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	16 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 programming visit

Population: Therapeutic window for current steering settings was not a primary outcome measure but is described later as an "Other" outcome measure.

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.

Outcome measures

Measure	Short PW n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=15 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Therapeutic Window	3.81 mA Standard Deviation 2.78	2.32 mA Standard Deviation 1.45	—	—

PRIMARY outcome

Timeframe: Day 1 programming visit

Population: All subjects were analyzed at both pulse widths. Primary outcomes were only intended to be assessed for different pulse widths and not current steering.

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.

Outcome measures

Measure	Short PW n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=15 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Unified Parkinson's Disease Rating Scale III	31.9 UPDRS III score Standard Deviation 11.55	31.3 UPDRS III score Standard Deviation 10.99	—	—

SECONDARY outcome

Timeframe: Day 1 programming visit

Population: The 24 patients reported here are a separate population from the 16 patients who were enrolled for primary endpoint analysis (40 total patients).

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).

Outcome measures

Measure	Short PW n=24 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=24 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Side Effect Thresholds - Single Contact vs. Steering	5.3 mA Standard Deviation 2.3	5.2 mA Standard Deviation 1.8	—	—

SECONDARY outcome

Timeframe: Day 1 programming visit

Population: The 24 patients reported here are a separate population from the 16 patients who were enrolled for primary endpoint analysis (40 total patients).

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).

Outcome measures

Measure	Short PW n=24 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=24 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Resting Tremor Severity - Single Contact vs. Steering	0.2 units on a scale Standard Deviation 0.6	0.2 units on a scale Standard Deviation 0.6	—	—

SECONDARY outcome

Timeframe: Day 1 programming visit

Population: The 24 patients reported here are a separate population from the 16 patients who were enrolled for primary endpoint analysis (40 total patients).

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).

Outcome measures

Measure	Short PW n=24 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=24 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Finger Tapping Amplitude - Single Contact vs. Steering	2.2 units on a scale Standard Deviation 0.9	2.3 units on a scale Standard Deviation 0.7	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 programming visit

Population: The therapeutic window of short pulse widths vs. conventional pulse widths was a primary outcome measure and is reported as such in another section of this report.

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).

Outcome measures

Measure	Short PW n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=15 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering Patients with a Vercise DBS system programmed to steer current dorsally
Dorsal-Ventral Current Steering Therapeutic Window	2.05 mA Standard Deviation 1.82	2.56 mA Standard Deviation 2.76	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Measure	Short PW n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=15 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering n=15 Participants Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering n=15 Participants Patients with a Vercise DBS system programmed to steer current dorsally
Resting Tremor Severity - Pulse Width and Dorsal-Ventral Steering	0.25 units on a scale Standard Deviation 0.63	0.34 units on a scale Standard Deviation 0.71	0.13 units on a scale Standard Deviation 0.34	0.30 units on a scale Standard Deviation 0.62

OTHER_PRE_SPECIFIED outcome

Timeframe: 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).

Outcome measures

Measure	Short PW n=15 Participants Patients with a Vercise DBS system programmed to 30 microseconds pulse width	Conventional PW n=15 Participants Patients with a Vercise DBS system programmed to 60 microseconds pulse width	Ventral Current Steering n=15 Participants Patients with a Vercise DBS system programmed to steer current ventrally	Dorsal Current Steering n=15 Participants Patients with a Vercise DBS system programmed to steer current dorsally
Finger Tapping Amplitude - Pulse Width and Dorsal-Ventral Steering	2.16 units on a scale Standard Deviation 0.74	2.20 units on a scale Standard Deviation 0.63	2.17 units on a scale Standard Deviation 0.77	2.16 units on a scale Standard Deviation 0.73

Adverse Events

All Arms

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Stephen Carcieri, PhD

Boston Scientific

Phone: 661-949-4756

Email: Stephen.Carcieri@bsci.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place