- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03582891
The Motor Network in Parkinson's Disease and Dystonia: Mechanisms of Therapy
Closed Loop Deep Brain Stimulation in Parkinson's Disease and Dystonia (Activa RC+S)
This is an exploratory pilot study to identify neural correlates of specific motor signs in Parkinson's disease (PD) and dystonia, using a novel totally implanted neural interface that senses brain activity as well as delivering therapeutic stimulation. Parkinson's disease and isolated dystonia patients will be implanted unilaterally or bilaterally with a totally internalized bidirectional neural interface, Medtronic Summit RC+S.
This study includes three populations: ten PD patients undergoing deep brain stimulation in the subthalamic nucleus (STN), ten PD patients with a globus pallidus (GPi) target and five dystonia patients. All groups will test a variety of strategies for feedback-controlled deep brain stimulation, and all patients will undergo a blinded, small pilot clinical trial of closed-loop stimulation for thirty days.
Study Overview
Status
Conditions
Detailed Description
In this project investigators will develop adaptive DBS algorithms based on cortical and subcortical signals using the RC+S. This bidirectional neural interface is rechargeable (for up to 9 years of use), and is capable of delivering therapeutic open-loop stimulation or closed-loop stimulation. Its sensing capability includes four simultaneous time series channels at up to 1000 Hz sampling rate. In addition the device can stream time series data, and calculate and stream spectral power within a preset bandwidth. Twenty patients with idiopathic PD and motor fluctuations, or medically intractable tremor, will be implanted with unilateral or bilateral RC+S devices, each connected to a standard quadripolar DBS lead implanted in STN or globus pallidus, and to a 4-contact paddle type electrode placed subdurally over sensorimotor cortex. The basal ganglia lead will be used for both stimulation and LFP recordings, while the cortical lead will be used only for recording ECoG potentials, not for stimulation.
Patients with motor fluctuations cycle between a hypokinetic state (too little movement) and a hyperkinetic state (excessive movement). During open-loop DBS, brain state continues to fluctuate between these states and stimulation may induce dyskinesia or inadequately relieve akinesia.
With the goal of maintaining motor function within a normal range away from these two extremes, investigators will develop and test stimulation algorithms that utilize putative markers of both kinetic states. Investigators will also study neural signals of sleep and test stimulation to support specific sleep stages. The basic strategy is to automatically adjust stimulation parameters until the physiological signature of abnormal function is minimized. First, investigators will prototype adaptive stimulation paradigms and briefly (2 hours) test them in clinic, using a "distributed" configuration (streaming to a computer). Then, investigators will embed these algorithms in RC+S to test chronic and fully closed-loop DBS in a small double-blinded clinical trial. Investigators will pay careful attention to the possibility of progressive reduction in stimulation currents over the course of the study, which could support the hypothesis that "adaptive stimulation" might make the brain progressively less dependent on the device. In quantifying DBS amplitude and comparing open loop with adaptive stimulation, an important parameter is the total electrical energy delivered (TEED). TEED is calculated by the following equation as suggested by Koss and colleagues (TEED1sec = ((voltage2 x frequency x pulsewidth)/impedance) x 1sec). This can be used as measure of the energy saved when stimulation is delivered in closed-loop mode relative to empiric open-loop stimulation.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Sarah Wang, PhD
- Phone Number: 415-353-7885
- Email: Sarah.Wang@ucsf.edu
Study Contact Backup
- Name: Robert Wilt
- Email: Robert.Wilt@ucsf.edu
Study Locations
-
-
California
-
San Francisco, California, United States, 94115
- University of California at San Francisco
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
Parkinson's Disease:
- Ability to give informed consent for the study
- Movement disorder symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
- Patient has requested surgical intervention with deep brain stimulation for their disorder
- No MR abnormalities that suggest an alternative diagnosis or contraindicate surgery
- Absence of significant cognitive impairment (score of 20 or greater on the Montreal Cognitive Assessment (MoCA),
- Signed informed consent
- Ability to comply with study follow-up visits for brain recording, testing of adaptive stimulation, and clinical assessment.
- Age 21-75 (for STN patients, minimum age is 25)
- Diagnosis of idiopathic PD with duration of motor symptoms for 4 years or greater
- Patient has undergone appropriate therapy with oral medications with inadequate relief as determined by a movement disorders neurologist, and has had stable doses of antiparkinsonian medications for 30 days prior to baseline assessment.
- UPDRS-III score off medication between 20 and 80 and an improvement of at least 30% in the baseline UPDRS-III on medication score, compared to the baseline off-medication score, and motor fluctuations with at least 2 hours per day of on time without dyskinesia or with non-bothersome dyskinesia.
OR Patients with tremor-dominant PD (a tremor score of at least 2 on a UPDRS-III sub-score for tremor), treatment resistant, with significant functional disability despite maximal medical management
Dystonia:
- Ability to give informed consent for the study
- Movement disorder symptoms that are sufficiently severe, in spite of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
- Patient has requested surgical intervention with deep brain stimulation for their disorder
- No MR abnormalities that suggest an alternative diagnosis or contraindicate surgery
- Absence of significant cognitive impairment (score of 20 or greater on the Montreal Cognitive Assessment (MoCA)
- Signed informed consent
- Ability to comply with study follow-up visits for brain recording, testing of adaptive stimulation, and clinical assessment.
- Age 21-75
- Diagnosis of Isolated dystonia, which may be focal cervical, segmental craniocervical, or generalized forms.
- Stable doses of anti-dystonia medications (such as trihexyphenydil, Baclofen, or clonazepam) for at least 30 days prior to baseline assessment
- For dystonia patients with craniofacial and cervical involvement, prior treatment with botulinum toxin with failure to adequately control dystonia symptoms.
Exclusion Criteria
Parkinson's Disease:
- Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of seizures, heart disease, or other medical conditions considered to place the patient at elevated risk for surgical complications
- Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion or "while unobserved", symptoms that are inconsistent over time or incongruent with clinical condition, plus other manifestation such as "false" signs, multiple somatizations, or obvious psychiatric disturbance.
- Pregnancy: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure.
- Significant untreated depression (BDI-II score >20) History of suicidal attempt or active suicidal ideation (Yes to #2-5 on C-SSRS)
- Any personality or mood symptoms that study personnel believe will interfere with study requirements.
- Subjects who require ECT, rTMS or diathermy
- Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator, neurostimulator or metallic implant
- Previous cranial surgery
- Drug or alcohol abuse
- Meets criteria for Parkinson's disease with mild cognitive impairment (PD-MCI). These criteria are: performance of more than two standard deviations below appropriate norms, for tests from two or more of these five cognitive domains: attention, executive function, language, memory, and visuospatial tests.
Dystonia:
- Coagulopathy, anticoagulant medications, uncontrolled hypertension, history of seizures, heart disease, or other medical conditions considered to place the patient at elevated risk for surgical complications
- Evidence of a psychogenic movement disorder: Motor symptoms that remit with suggestion or "while unobserved", symptoms that are inconsistent over time or incongruent with clinical condition, plus other manifestation such as "false" signs, multiple somatizations, or obvious psychiatric disturbance.
- Pregnancy: all women of child bearing potential will have a negative urine pregnancy test prior to undergoing their surgical procedure.
- Significant untreated depression (BDI-II score >20) History of suicidal attempt or active suicidal ideation (Yes to #2-5 on C-SSRS)
- Any personality or mood symptoms that study personnel believe will interfere with study requirements.
- Subjects who require ECT, rTMS or diathermy
- Implanted stimulation systems such as; cochlear implant, pacemaker, defibrillator, neurostimulator or metallic implant
- Previous cranial surgery
- Drug or alcohol abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: Parkinson's Disease STN Target
Parkinson's disease patients implanted in STN
|
Using the RC+S pulse generator, investigators will measure cortical biomarkers of hyper and hypokinesia in Parkinson's and dystonia patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
These patients will participate in an 8 week clinical trial of open loop versus adaptive mode (4 weeks for each mode (interleaved), with the order counterbalanced across subjects ).
Using the RC+S pulse generator, investigators will measure cortical biomarkers of sleep stages in Parkinson's patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
Other Names:
|
Other: Parkinson's disease patients GP Target
Parkinson's disease patients implanted in Globus Pallidus
|
Using the RC+S pulse generator, investigators will measure cortical biomarkers of hyper and hypokinesia in Parkinson's and dystonia patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
These patients will participate in an 8 week clinical trial of open loop versus adaptive mode (4 weeks for each mode (interleaved), with the order counterbalanced across subjects ).
Using the RC+S pulse generator, investigators will measure cortical biomarkers of sleep stages in Parkinson's patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
Other Names:
|
Other: Dystonia patients
Isolated dystonia patients
|
Using the RC+S pulse generator, investigators will measure cortical biomarkers of hyper and hypokinesia in Parkinson's and dystonia patients to develop an adaptive algorithm which adjusts the level of deep brain stimulation needed based upon the patient's physiology.
These patients will participate in an 8 week clinical trial of open loop versus adaptive mode (4 weeks for each mode (interleaved), with the order counterbalanced across subjects ).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of 'on' stimulation time without dyskinesia from motor diaries in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Duration of 'on' stimulation time without dyskinesia in adaptive compared to standard open loop stimulation determined from the patients' motor diaries.
The self-report motor diary is a validated method to capture this information.
Every half-hour, patients indicate in this diary which of 4 categories (on, on with troubling dyskinesia, off, or asleep) best reflected their predominant symptoms for the prior 30 minutes.
Patients will complete this diary for 3 consecutive days.
The total time spent in the 'on' state without troubling dyskinesia will then be summed and averaged over 3 days for all three conditions (baseline, open-loop stimulation and closed-loop stimulation).
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The Burke-Fahn-Marsden Dystonia Rating Scale-Movement aDBS testing compared to pre-operative baseline(Dystonia Patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
This scales evaluates dystonia in nine body areas, including eyes, mouth, speech and swallowing, neck, trunk, and right and left arm and leg.
The maximal total score is 120 - a higher score means worsening symptoms.
Investigators will compare the dystonia symptoms and functional disability during adaptive stimulation compared to preoperative baseline.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Toronto Western Spasmodic Torticollis Rating Scale during aDBS testing compared to pre-operative baseline (Dystonia Patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
This is a standardized scale to measure the severity, disability, and pain associated with cervical dystonia.
The motor severity subscale consists of 10 items, with variable scaling and weighting.
It also includes a disability scale with six items,and a pain scale with three items.
The total score is the sum of each of the subscales.
A higher score indicates greater disability.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Karolinska Sleepiness Scale
Time Frame: Through study completion, up to 4 years
|
This is a standardized scale for measuring sleepiness
|
Through study completion, up to 4 years
|
Psychomotor vigilance task (PVT)
Time Frame: Through study completion, up to 4 years
|
This is a standardized behavioral task for measure alertness and attention
|
Through study completion, up to 4 years
|
Positive and Negative Affect Schedule (PANAS-SF)
Time Frame: Through study completion, up to 4 years
|
This is a standardized mood questionnaire
|
Through study completion, up to 4 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The Unified Parkinsons Disease Rating Scale (UPDRS) III scores off of medication in adaptive compared to standard open-loop stimulation. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The UPDRS III is a motor rating scale.
Investigators will compare the severity motor symptoms while the patient is off of Parkinsoniae (UPDRS) III scores off of medication in adaptive compared to standard open-loop stimulation.
(Parkinson's disease patients)n medications in conventional (open-loop) versus adaptive (closed-loop) DBS.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Schwab England scale in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
This scale estimates the abilities of individuals living with Parkinson's Disease relative to a completely independent situation.
Investigators will use it to compare the abilities of daily living in subjects during the open-loop and adaptive stimulation trial.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Hoehn and Yahr Staging in the medication 'on' state in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The Hoehn and Yahr scale are used to describe the progression of Parkinson's disease based upon the level of motor impairment.
This scale only includes one score ranging from 1 to 5 where a higher score indicates a higher level of motor impairment.
Investigators will compare the level of disease progression between the open-loop and adaptive stimulation conditions.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The patient' quality of life report (PDQ-39) in adaptive compared to standard open loop stimulation. The PDQ39 yields a score between 0 to 100, where a higher score indicates more health problems. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The PDQ 39 questionnaire has 39 questions to assess the patient's life quality including mobility, emotional state, and bodily comfort.
Investigators will make a comparison of patients' life quality of life between open-loop and adaptive stimulation.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Patient's Global Impression of Change (PGIC) in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Patient Global Impression of Changes measures the self-reported level of overall improvement (motor and non-motor symptoms) in a patient on a 1-7 scale.
A one indicates no change and a 7 is the greatest level of improvement.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Total Electric Energy Delivered (TEED) by the pulse generator in adaptive compared to standard open loop stimulation. (all patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Investigators will compare the total charge delivered by the pulse generator between open-loop and adaptive stimulation to determine if there is a potential energy savings.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Short form 36 Quality of Life measure (Dystonia Patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
The SF-36 is a measure of self-reported health status which is scored on a 0-100 scale.
The lower the score the more disability a patient experiences.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Patient Global Impression of Change (Dystonia Patients)
Time Frame: Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Patient Global Impression of Changes measures the self-reported level of overall improvement (motor and non-motor symptoms) in a patient on a 1-7 scale.
A one indicates no change and a 7 is the greatest level of improvement.
|
Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.
|
Resting state EEG Recording
Time Frame: Through study completion, up to 4 years
|
Resting state cortical power will be analyzed as a surrogate marker of alertness
|
Through study completion, up to 4 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Philip A Starr, MD/PhD, University of California, San Francisco
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UCSF Summit RC+S
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Parkinson Disease
-
National Heart, Lung, and Blood Institute (NHLBI)CompletedParkinson Disease 6, Early-Onset | Parkinson Disease (Autosomal Recessive, Early Onset) 7, Human | Parkinson Disease Autosomal Recessive, Early Onset | Parkinson Disease, Autosomal Recessive Early-Onset, Digenic, Pink1/Dj1United States
-
ProgenaBiomeRecruitingParkinson Disease | Parkinsons Disease With Dementia | Parkinson-Dementia Syndrome | Parkinson Disease 2 | Parkinson Disease 3 | Parkinson Disease 4United States
-
King's College LondonGlaxoSmithKlineCompletedParkinson Disease | Idiopathic Parkinson Disease | Parkinson Disease, PARK8United Kingdom
-
Ohio State UniversityCompletedParkinson's Disease | Parkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease | Parkinson Disease, Idiopathic | Parkinson's Disease, IdiopathicUnited States
-
National Yang Ming UniversityUnknownEarly Onset Parkinson Disease | Early Stage Parkinson Disease
-
Michele Tagliati, MDRecruitingREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Cedars-Sinai Medical CenterEnrolling by invitationREM Sleep Behavior Disorder | Symptomatic Parkinson Disease | Pre-motor Parkinson DiseaseUnited States
-
Mahatma Gandhi Institute of Medical SciencesCompletedStroke, Parkinson' s Disease, Neurological Impairments, Tele-rehabilitationIndia
-
Merck Sharp & Dohme LLCCompletedParkinson Disease | Idiopathic Parkinson Disease | Idiopathic Parkinson's Disease
-
University of DeustoCompletedPARKINSON DISEASE (Disorder)Spain
Clinical Trials on Summit RC+S for Motor
-
University of California, San FranciscoNational Institute of Neurological Disorders and Stroke (NINDS)Active, not recruitingPain, Postoperative | Complex Regional Pain Syndromes | Spinal Cord Injuries | Nerve Injury | Post Herpetic Neuralgia | Post-Stroke Pain | Post Radiation Brain Injury | Post Radiation Plexopathy | Nerve Root AvulsionUnited States
-
Helen Mayberg, MDNational Institute of Neurological Disorders and Stroke (NINDS); Emory University and other collaboratorsActive, not recruitingMajor Depressive Disorder | Treatment Resistant DepressionUnited States
-
Baylor College of MedicineNational Institute of Neurological Disorders and Stroke (NINDS); University... and other collaboratorsActive, not recruitingObsessive-Compulsive DisorderUnited States
-
Doris Wang, MD, PhDMichael J. Fox Foundation for Parkinson's Research; Burroughs WellcomeActive, not recruitingParkinson DiseaseUnited States
-
Baylor College of MedicineNational Institute of Neurological Disorders and Stroke (NINDS); University... and other collaboratorsActive, not recruitingObsessive-Compulsive DisorderUnited States
-
University of FloridaNational Institute of Neurological Disorders and Stroke (NINDS); MedtronicRecruitingEssential TremorUnited States
-
University of FloridaNational Institute of Neurological Disorders and Stroke (NINDS); MedtronicActive, not recruiting
-
Dennis Turner, M.D.National Institute of Neurological Disorders and Stroke (NINDS); National Institutes...Completed
-
University of MinnesotaWithdrawnParkinson Disease | ParkinsonUnited States
-
El Instituto Nacional de Neurologia y Neurocirugia...CompletedPost Traumatic Stress Disorder | Trauma, PsychologicalMexico