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

NCT02384421 | Completed Results DMC

• 1 other identifier: 30880
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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Scale (UPDRS III) and specific phenotypic measures in Parkinson's Disease compared to OFF therapy (i.e., OFF DBS and withdrawn from medication) and more efficient than cDBS.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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  30 minutes

Secondary Outcomes (4)

• Disease Symptoms (Tremor)

  30 minutes

• Disease Symptoms (Freezing of Gait)

  30 minutes

• Disease Symptoms (Bradykinesia)

  30 minutes

• DBS Voltage

  30 minutes

Study Arms (1)

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

Device: Adaptive DBS (Activa PC+S Neurostimulator); Device: Continuous DBS (Activa PC+S Neurostimulator)

Interventions

Adaptive DBS (Activa PC+S Neurostimulator) DEVICE

Also known as: Adaptive deep brain stimulation

Activa PC+S Neurostimulator

Continuous DBS (Activa PC+S Neurostimulator) DEVICE

Also known as: continuous deep brain stimulation

Activa PC+S Neurostimulator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford Movement Disorders Center

Stanford, California, 94305-5235, United States

Location

Related Publications (3)

• 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.

  PMID: 30833216 RESULT

• 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.

  PMID: 26813875 RESULT

• 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.

  PMID: 32634599 RESULT

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: Dr. Helen Bronte-Stewart, MD, MSE
• Organization: Stanford University

bronte-stewart-lab@stanford.edu

650-723-6709

Study Officials

• Helen Bronte-Stewart, MD MSE

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD MSE

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: March 10, 2015
• Study Start: January 1, 2015
• Primary Completion: September 23, 2019
• Study Completion: August 16, 2021
• Last Updated: February 1, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-01

Locations

US (1)