Parkinson's DiseaseaDBSNCT02384421

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

A study testing Adaptive DBS (Activa PC+S Neurostimulator) and Continuous DBS (Activa PC+S Neurostimulator) in people with Parkinson's Disease, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Parkinson's Disease
What is being tested?: Adaptive DBS (Activa PC+S Neurostimulator) and Continuous DBS (Activa PC+S Neurostimulator)
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 22 participants
Where: 1 siteUnited States
Study dates: Jan 2015to 16 Aug 2021
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
Documented improvement in motor signs on versus off dopaminergic medication, with a change in the Unified Parkinson's Disease Rating Scale motor (UPDRS III) score of >= 30% off to on medication.
The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
Subjects should be on stable doses of medications, which should remain unchanged until the DBS system is activated. After the DBS system is optimized (during which time the overall medication dose may be reduced to avoid discomfort and complications such as dyskinesias) the medication dose should remain unchanged, if possible, for the duration of the study.
Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.
Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
Age > 18

Who cannot join

Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
Subjects with clinically active depression, defined according to the Diagnostic and Statistical manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and as scored on a validated depression assessment scale.
Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
Age > 80.
Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.
Subjects, who are pregnant, are capable of becoming pregnant, or who are breast feeding.

Show all 15Show fewer

Patients with cortical atrophy out of proportion to age or focal brain lesions that could indicate a non-idiopathic movement disorder as determined by MRI
Subjects having a major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin).
Subjects having any prior intracranial surgery.
Subjects with a history of seizures.
Subjects, who are immunocompromised.
Subjects with an active infection.
Subjects, who require diathermy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) to treat a chronic condition.
Subjects, who have an inability to comply with study follow-up visits.
Subjects, who are unable to understand or sign the informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

Stanford Movement Disorders Center
Stanford, California, 94305-5235

Other trials in United States

About this study

Continuous deep brain stimulation (cDBS) is an established therapy for the major motor signs in Parkinson's disease. Currently, cDBS is limited to "open-loop" stimulation, without real-time adjustment to the patient's state of activity, fluctuations and types of motor symptoms, medication dosages, or neural markers of the disease. The purpose of this study is to determine if an adaptive DBS system, responding to patient specific, clinically relevant neural or kinematic feedback, is efficacious on the motor Unified Parkinson's Disease Rating Scale (UPDRS III) and specific phenotypic measures in Parkinson's Disease compared to OFF therapy (i.e., OFF DBS and withdrawn from medication) and more efficient than cDBS. Not every recruited participant completed every part of the protocol.

Conditions: Parkinson's Disease
Being tested: Adaptive DBS (Activa PC+S Neurostimulator), Continuous DBS (Activa PC+S Neurostimulator)
Medical subject headings: Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Adaptive DBS (Activa PC+S Neurostimulator)Device
Also called Adaptive deep brain stimulation
Continuous DBS (Activa PC+S Neurostimulator)Device
Also called continuous deep brain stimulation

Study groups in NCT02384421
Study group	Role	What they receive
Activa PC+S Neurostimulator	Experimental	Participants will be own controls and undergo both adaptive and continuous deep brain stimulation testing paradigms using Nexus D research tool PC+S: Primary Cell+Sensing Receives: Device: Adaptive DBS (Activa PC+S Neurostimulator); Device: Continuous DBS (Activa PC+S Neurostimulator)

What is being measured

The primary outcome is the main question the study is designed to answer.

Normalized Beta Band Power (13-30 Hz) During aDBS
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.
Measured: 30 minutes
Change in UPDRS III Score
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.
Measured: 30 minutes

Secondary outcomes (4)

Disease Symptoms (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.
Measured: 30 minutes
Disease Symptoms (Freezing of Gait)
Percent time freezing during a stepping-in-place task. Higher percent time freezing represents a worse outcome.
Measured: 30 minutes
Disease Symptoms (Bradykinesia)
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.
Measured: 30 minutes
DBS Voltage
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.
Measured: 30 minutes

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 201516 Aug 2021

First posted10 Mar 2015 (estimated)
Study startJan 2015
Primary completion23 Sep 2019
Study completion16 Aug 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02384421
Sponsor's protocol ID: 30880
Acronym: aDBS
Status last verified: Jan 2022
First submitted: 18 Feb 2015
Last updated: 1 Feb 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimul. 2019 Jul-Aug;12(4):868-876. doi: 10.1016/j.brs.2019.02.020. Epub 2019 Feb 25.
PubMed 30833216
Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Bronte-Stewart H. Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Mov Disord. 2016 Mar;31(3):426-8. doi: 10.1002/mds.26482. Epub 2016 Jan 27. No abstract available.
PubMed 26813875
Petrucci MN, Neuville RS, Afzal MF, Velisar A, Anidi CM, Anderson RW, Parker JE, O'Day JJ, Wilkins KB, Bronte-Stewart HM. Neural closed-loop deep brain stimulation for freezing of gait. Brain Stimul. 2020 Sep-Oct;13(5):1320-1322. doi: 10.1016/j.brs.2020.06.018. Epub 2020 Jul 4. No abstract available.
PubMed 32634599

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
ClinicalTrials.gov ID: NCT02384421
Acronym / sponsor ID: aDBS / 30880
Conditions: Parkinson's Disease
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Study start: Jan 2015
Primary completion: 23 Sep 2019 (actual)
Study completion: 16 Aug 2021 (actual)
First posted: 10 Mar 2015 (estimated)
Results: Posted 1 Feb 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Activa PC+S Neurostimulator	Experimental	Device: Adaptive DBS (Activa PC+S Neurostimulator), Device: Continuous DBS (Activa PC+S Neurostimulator)Participants will be own controls and undergo both adaptive and continuous deep brain stimulation testing paradigms using Nexus D research tool PC+S: Primary Cell+Sensing

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
Documented improvement in motor signs on versus off dopaminergic medication, with a change in the Unified Parkinson's Disease Rating Scale motor (UPDRS III) score of >= 30% off to on medication.
The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
Subjects should be on stable doses of medications, which should remain unchanged until the DBS system is activated. After the DBS system is optimized (during which time the overall medication dose may be reduced to avoid discomfort and complications such as dyskinesias) the medication dose should remain unchanged, if possible, for the duration of the study.
Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.

Key exclusion criteria (15 listed)

Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
Subjects with clinically active depression, defined according to the Diagnostic and Statistical manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and as scored on a validated depression assessment scale.
Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
Age > 80.
Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Adaptive DBS (Activa PC+S Neurostimulator)Also: Adaptive deep brain stimulation	Device	Activa PC+S Neurostimulator
Continuous DBS (Activa PC+S Neurostimulator)Also: continuous deep brain stimulation	Device	Activa PC+S Neurostimulator

Primary outcome

Normalized Beta Band Power (13-30 Hz) During aDBS
Time frame: 30 minutes
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.
Change in UPDRS III Score
Time frame: 30 minutes
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.

4 secondary outcomes

Disease Symptoms (Tremor)
Time frame: 30 minutes
Disease Symptoms (Freezing of Gait)
Time frame: 30 minutes
Disease Symptoms (Bradykinesia)
Time frame: 30 minutes
DBS Voltage
Time frame: 30 minutes

Results and safety

Results posted to the registry on 1 Feb 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Activa PC+S Neurostimulator	22	22

Primary outcome: Normalized Beta Band Power (13-30 Hz) During aDBS

Time frame: 30 minutes. Mean (Standard Deviation). Unit: Normalized median beta power

Measure	Activa PC+S Neurostimulator n = 13
Value	0.26 (0.14)

Activa PC+S Neurostimulator: p <0.001, t-test, 2 sided

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

Primary outcome: Change in UPDRS III Score

Time frame: 30 minutes. Mean (Standard Deviation). Unit: score on a scale

Measure	Activa PC+S Neurostimulator n = 8
OFF	28.1 (17.1)
aDBS	12.5 (10.5)

Activa PC+S Neurostimulator: p = 0.0064, t-test, 2 sided

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

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to six years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Activa PC+S Neurostimulator	4 of 22 (18.2%)	20 of 22 (90.9%)	1 of 22

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 30833216Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimul. 2019 Jul-Aug;12(4):868-876. doi: 10.1016/j.brs.2019.02.020. Epub 2019 Feb 25.
Results publication: PubMed 26813875Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Bronte-Stewart H. Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Mov Disord. 2016 Mar;31(3):426-8. doi: 10.1002/mds.26482. Epub 2016 Jan 27. No abstract available.
Results publication: PubMed 32634599Petrucci MN, Neuville RS, Afzal MF, Velisar A, Anidi CM, Anderson RW, Parker JE, O'Day JJ, Wilkins KB, Bronte-Stewart HM. Neural closed-loop deep brain stimulation for freezing of gait. Brain Stimul. 2020 Sep-Oct;13(5):1320-1322. doi: 10.1016/j.brs.2020.06.018. Epub 2020 Jul 4. No abstract available.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Helen Bronte-Stewart, MD MSE principal investigator

Stanford University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Adaptive DBS (Activa PC+S Neurostimulator) and Continuous DBS (Activa PC+S Neurostimulator) in people with Parkinson's Disease, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Normalized Beta Band Power (13-30 Hz) During aDBS (time frame: 30 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02384421, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2022.