Trial Outcomes & Findings for Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease (NCT NCT02384421)

NCT ID: NCT02384421

Last Updated: 2022-02-01

Results Overview

Beta Band Power will be recorded continuously during intervention (30 minutes). The PC+S streams off power of the local field potential signal measured from the subthalamic nucleus in a frequency band of interest within the beta band (13-30 Hz). The amplitude of the signal, beta power, was streamed from each subthalamic nucleus (STN) during the calibration period of the experiment when DBS was off (i.e., OFF therapy), when continuous DBS was set at the lower and upper stimulation voltage that were found for determining the stimulation limits of adaptive DBS, and during the 30 minutes of aDBS. We calculated the median observed beta power during aDBS. To compute normalized beta band power, the median value was divided by the observed beta power OFF therapy and during the continuous DBS at the lower and upper voltage. A value less than 1 indicates reduced beta power during aDBS compared to the other conditions.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

22 participants

Primary outcome timeframe

30 minutes

Results posted on

2022-02-01

Participant Flow

Participant milestones

Participant milestones
Measure
Activa PC+S Neurostimulator
Participants will be own controls and undergo both Adaptive DBS (Activa PC+S Neurostimulator) and Continuous DBS (Activa PC+S Neurostimulator) deep brain stimulation testing paradigms using Nexus D research tool PC+S: Primary Cell+Sensing
Overall Study
STARTED
22
Overall Study
COMPLETED
22
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Activa PC+S Neurostimulator
n=22 Participants
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Age, Continuous
58.6 years
STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
Sex: Female, Male
Male
16 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
19 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
19 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
Region of Enrollment
United States
22 Participants
n=5 Participants
Mean OFF UPDRS-III at Initial Programming
41.9 UPDRS-III Score
STANDARD_DEVIATION 15.4 • n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome and with no artifacts in the local field potential signal.

Beta Band Power will be recorded continuously during intervention (30 minutes). The PC+S streams off power of the local field potential signal measured from the subthalamic nucleus in a frequency band of interest within the beta band (13-30 Hz). The amplitude of the signal, beta power, was streamed from each subthalamic nucleus (STN) during the calibration period of the experiment when DBS was off (i.e., OFF therapy), when continuous DBS was set at the lower and upper stimulation voltage that were found for determining the stimulation limits of adaptive DBS, and during the 30 minutes of aDBS. We calculated the median observed beta power during aDBS. To compute normalized beta band power, the median value was divided by the observed beta power OFF therapy and during the continuous DBS at the lower and upper voltage. A value less than 1 indicates reduced beta power during aDBS compared to the other conditions.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=20 STNs
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Normalized Beta Band Power (13-30 Hz) During aDBS
0.26 Normalized median beta power
Standard Deviation 0.14

PRIMARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome (had a clinical UPDRS assessment).

Movement Disorder Society's Unified Parkinson's Disease Rating Scale III (UPDRS III) score will be measured after 30 minutes of intervention and compared to baseline. Scores on the UPDRS III range from 0-132. Higher scores represent a worse outcome. For some participants, a modified UPDRS III was used in which items 3.9, 3.10, 3.11, 3.12, and 3.13 were excluded to only focus on the seated portion of the assessment, or only one hemibody was tested if the aDBS controller was only controlling one subthalamic nucleus.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=8 Participants
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Change in UPDRS III Score
OFF
28.1 score on a scale
Standard Deviation 17.1
Change in UPDRS III Score
aDBS
12.5 score on a scale
Standard Deviation 10.5

SECONDARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome and not excluded due to lack of tremor.

Mean tremor power calculated from a triaxial gyroscope using a fast Fourier transform averaged between 4 and 8 Hz. Higher tremor power indicates worse tremor.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=10 STNs
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Disease Symptoms (Tremor)
OFF
0.040 (rad/s)^2
Standard Deviation 0.11
Disease Symptoms (Tremor)
aDBS
0.0072 (rad/s)^2
Standard Deviation 0.018

SECONDARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome and with no artifacts in the local field potential signal, artifacts in the kinematic data, or excluded since they did not identify as freezers.

Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=5 Participants
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Disease Symptoms (Freezing of Gait)
OFF
22 percentage of time freezing
Standard Deviation 30
Disease Symptoms (Freezing of Gait)
aDBS
0 percentage of time freezing
Standard Deviation 1

SECONDARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome and with no artifacts in the local field potential signal, substantial tremor in the tested limb, or technical issues during the kinematic recording.

The root mean squared of the angular velocity during a wrist-flexion extension task. Higher root mean squared of angular velocity represents a better outcome.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=13 Participants
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Disease Symptoms (Bradykinesia)
OFF
352.58 root mean squared of angular velocity
Standard Deviation 56.46
Disease Symptoms (Bradykinesia)
aDBS
457.44 root mean squared of angular velocity
Standard Deviation 58.96

SECONDARY outcome

Timeframe: 30 minutes

Population: Participants who were assessed for this outcome and with no artifacts in the local field potential signal.

The median stimulation voltage during the aDBS run was determined for each individual's subthalamic nucleus. The overall group mean of the median stimulation voltages was compared to the group mean of the clinical continuous DBS (cDBS) median voltages.

Outcome measures

Outcome measures
Measure
Activa PC+S Neurostimulator
n=20 STNs
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
DBS Voltage
Clinical Open Loop (cDBS)
3.12 median stimulation voltage
Standard Deviation 0.54
DBS Voltage
aDBS
2.03 median stimulation voltage
Standard Deviation 0.91

Adverse Events

Activa PC+S Neurostimulator

Serious events: 4 serious events
Other events: 20 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
Activa PC+S Neurostimulator
n=22 participants at risk
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Infections and infestations
Infection
4.5%
1/22 • Number of events 1 • Up to six years
Product Issues
Lead/Connection Break
4.5%
1/22 • Number of events 1 • Up to six years
Psychiatric disorders
Suicidality
4.5%
1/22 • Number of events 1 • Up to six years
Injury, poisoning and procedural complications
Femur fracture
4.5%
1/22 • Number of events 1 • Up to six years

Other adverse events

Other adverse events
Measure
Activa PC+S Neurostimulator
n=22 participants at risk
Participants will be own controls and undergo both Adaptive DBS and Continuous DBS deep brain stimulation
Product Issues
Device Failure
4.5%
1/22 • Number of events 1 • Up to six years
Infections and infestations
Infection
4.5%
1/22 • Number of events 1 • Up to six years
Surgical and medical procedures
Tenderness
4.5%
1/22 • Number of events 1 • Up to six years
Product Issues
Sensing Malfunction
4.5%
1/22 • Number of events 1 • Up to six years
Product Issues
Device Malfunction
9.1%
2/22 • Number of events 2 • Up to six years
Nervous system disorders
Gait Difficulties
4.5%
1/22 • Number of events 1 • Up to six years
Nervous system disorders
Speech
4.5%
1/22 • Number of events 1 • Up to six years
Nervous system disorders
Cognitive Difficulties
4.5%
1/22 • Number of events 1 • Up to six years
General disorders
Tingling
18.2%
4/22 • Number of events 4 • Up to six years
General disorders
Balance
22.7%
5/22 • Number of events 6 • Up to six years
Musculoskeletal and connective tissue disorders
Muscle Soreness
9.1%
2/22 • Number of events 2 • Up to six years
Musculoskeletal and connective tissue disorders
Muscle Contractions
45.5%
10/22 • Number of events 18 • Up to six years
Nervous system disorders
Cognitive Problems
22.7%
5/22 • Number of events 6 • Up to six years
Nervous system disorders
Speech Difficulties
59.1%
13/22 • Number of events 19 • Up to six years
Psychiatric disorders
Depression
13.6%
3/22 • Number of events 4 • Up to six years
Psychiatric disorders
Suicidal Ideation
4.5%
1/22 • Number of events 1 • Up to six years
Musculoskeletal and connective tissue disorders
Slowness
9.1%
2/22 • Number of events 3 • Up to six years
Musculoskeletal and connective tissue disorders
Stiffness
45.5%
10/22 • Number of events 16 • Up to six years
Musculoskeletal and connective tissue disorders
Walking Difficulty
72.7%
16/22 • Number of events 27 • Up to six years
Psychiatric disorders
Anxiety
13.6%
3/22 • Number of events 3 • Up to six years
General disorders
Pain/Soreness
18.2%
4/22 • Number of events 5 • Up to six years
Gastrointestinal disorders
Diverticulitis
4.5%
1/22 • Number of events 1 • Up to six years
Renal and urinary disorders
Urinary Issues
9.1%
2/22 • Number of events 2 • Up to six years
General disorders
Weight changes
22.7%
5/22 • Number of events 7 • Up to six years
Nervous system disorders
Sleep Difficulties
36.4%
8/22 • Number of events 12 • Up to six years
General disorders
Weakness
4.5%
1/22 • Number of events 1 • Up to six years
General disorders
Fatigue
22.7%
5/22 • Number of events 15 • Up to six years
Gastrointestinal disorders
Hernia
4.5%
1/22 • Number of events 1 • Up to six years
Gastrointestinal disorders
Difficult Swallowing/Salivation
27.3%
6/22 • Number of events 7 • Up to six years
Nervous system disorders
Stroke
4.5%
1/22 • Number of events 1 • Up to six years
Psychiatric disorders
Mood
13.6%
3/22 • Number of events 3 • Up to six years
Nervous system disorders
Dreaming
4.5%
1/22 • Number of events 1 • Up to six years
Infections and infestations
Cough/Throat
18.2%
4/22 • Number of events 4 • Up to six years
Gastrointestinal disorders
Nausea
4.5%
1/22 • Number of events 2 • Up to six years
General disorders
Dizziness
9.1%
2/22 • Number of events 2 • Up to six years
Nervous system disorders
Restless Leg
9.1%
2/22 • Number of events 2 • Up to six years
General disorders
Headache/Migraine
9.1%
2/22 • Number of events 2 • Up to six years
Psychiatric disorders
Delerium
4.5%
1/22 • Number of events 1 • Up to six years
Eye disorders
Vision problems
18.2%
4/22 • Number of events 4 • Up to six years
Renal and urinary disorders
Kidney Issues
4.5%
1/22 • Number of events 1 • Up to six years
Cardiac disorders
Blood Pressure
4.5%
1/22 • Number of events 1 • Up to six years
General disorders
Body Temperature
13.6%
3/22 • Number of events 4 • Up to six years
Skin and subcutaneous tissue disorders
Hair Loss
4.5%
1/22 • Number of events 1 • Up to six years

Additional Information

Dr. Helen Bronte-Stewart, MD, MSE

Stanford University

Phone: 650-723-6709

Results disclosure agreements

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