The Motor Network in Parkinson's Disease and Dystonia: Mechanisms of Therapy

NCT03582891 | Active Not Recruiting DMC FDA Device

• 1 other identifier: UCSF Summit RC+S
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson Disease; Dystonia

Outcome Measures

Primary Outcomes (6)

• Duration of 'on' stimulation time without dyskinesia from motor diaries in adaptive compared to standard open loop stimulation. (Parkinson's disease patients)

  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)

  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)

  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

  This is a standardized scale for measuring sleepiness

  Through study completion, up to 4 years

• Psychomotor vigilance task (PVT)

  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)

  This is a standardized mood questionnaire

  Through study completion, up to 4 years

Secondary Outcomes (9)

• The Unified Parkinsons Disease Rating Scale (UPDRS) III scores off of medication in adaptive compared to standard open-loop stimulation. (Parkinson's disease patients)

  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)

  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)

  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)

  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)

  Comparison will use data from the testing of open and closed-loop stimulation during chronic adaptive DBS testing at home.

Study Arms (3)

Parkinson's Disease STN Target

OTHER

Parkinson's disease patients implanted in STN

Device: Summit RC+S for Motor; Diagnostic Test: 8-week pilot trial of Closed-loop vs. Open-loop Stimulation; Device: Summit RC+S for Sleep

Parkinson's disease patients GP Target

OTHER

Parkinson's disease patients implanted in Globus Pallidus

Device: Summit RC+S for Motor; Diagnostic Test: 8-week pilot trial of Closed-loop vs. Open-loop Stimulation; Device: Summit RC+S for Sleep

Dystonia patients

OTHER

Isolated dystonia patients

Device: Summit RC+S for Motor; Diagnostic Test: 8-week pilot trial of Closed-loop vs. Open-loop Stimulation

Interventions

Summit RC+S for Motor DEVICE

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.

Dystonia patients; Parkinson's Disease STN Target; Parkinson's disease patients GP Target

8-week pilot trial of Closed-loop vs. Open-loop Stimulation DIAGNOSTIC_TEST

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 ).

Dystonia patients; Parkinson's Disease STN Target; Parkinson's disease patients GP Target

Summit RC+S for Sleep DEVICE

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.

Also known as: Sleep

Parkinson's Disease STN Target; Parkinson's disease patients GP Target

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

University of California at San Francisco

San Francisco, California, 94115, United States

Location

Related Publications (3)

• Oehrn CR, Cernera S, Hammer LH, Shcherbakova M, Yao J, Hahn A, Wang S, Ostrem JL, Little S, Starr PA. Chronic adaptive deep brain stimulation versus conventional stimulation in Parkinson's disease: a blinded randomized feasibility trial. Nat Med. 2024 Nov;30(11):3345-3356. doi: 10.1038/s41591-024-03196-z. Epub 2024 Aug 19.

  PMID: 39160351 DERIVED

• Louie KH, Gilron R, Yaroshinsky MS, Morrison MA, Choi J, de Hemptinne C, Little S, Starr PA, Wang DD. Cortico-Subthalamic Field Potentials Support Classification of the Natural Gait Cycle in Parkinson's Disease and Reveal Individualized Spectral Signatures. eNeuro. 2022 Nov 11;9(6):ENEURO.0325-22.2022. doi: 10.1523/ENEURO.0325-22.2022. Print 2022 Nov-Dec.

  PMID: 36270803 DERIVED

• Powell MP, Anso J, Gilron R, Provenza NR, Allawala AB, Sliva DD, Bijanki KR, Oswalt D, Adkinson J, Pouratian N, Sheth SA, Goodman WK, Jones SR, Starr PA, Borton DA. NeuroDAC: an open-source arbitrary biosignal waveform generator. J Neural Eng. 2021 Feb 5;18(1):10.1088/1741-2552/abc7f0. doi: 10.1088/1741-2552/abc7f0.

  PMID: 33152715 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Dystonia

Interventions

Polysomnography

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Monitoring, Physiologic; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Philip A Starr, MD/PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Subjects with Parkinson's disease who are being implanted in the STN will be blinded to the type of stimulation received (open-loop or closed-loop phases) during the chronic adaptive DBS testing phase (period 4) at home. Each of these subjects will have blinded open-loop or closed-loop stimulation for a total of one month. The use of objective measures of motor function such as wearable devices, in addition physician administered rating scales, is a strategy to reduce observer bias. For physician administered scales, all exams will be videotaped so that these can be reviewed by a blinded neurologist evaluator.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Endowed Professor of Neurological Surgery

Model Details: Investigators will run a pilot clinical trial in which individualized classifier/control strategies for each hemisphere in each subject will be embedded within the RC+S for a total of one month (x4 one week blocks) of feedback-controlled stimulation will be compared with a total of one month of empirically optimized open-loop stimulation, (x4 one week blocks), administered in randomized order with adaptive stimulation. During these 1-month trials, patients and neurologists will be blinded to the state of the stimulator.

Study Record Dates

• First Submitted: June 14, 2018
• First Posted: July 11, 2018
• Study Start: October 1, 2018
• Primary Completion: December 31, 2025
• Study Completion (Estimated): March 1, 2028
• Last Updated: April 13, 2025

Record last verified: 2025-04

Locations

US (1)