Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04563143 |
| Other study ID # |
19-1637 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 17, 2020 |
| Est. completion date |
September 7, 2023 |
Study information
| Verified date |
October 2023 |
| Source |
The Cleveland Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Investigators will enroll patients who are already selected to undergo deep brain stimulation
surgery based on standard of care. The surgical implantation of the leads will be based on
standard of care and will be completed with FDA-approved leads that are routinely used at
Cleveland Clinic. The pulse generators (i.e. the battery) will also be standard. The research
will characterize spontaneous and task-related changes in brain activity recorded from these
regions alone and in relation to novel paradigms / settings of stimulation to learn how such
paradigms impact both the symptoms of patients with Parkinson's disease and the underlying
neural activity of the target brain region. Of particular interest is to learn if the novel
paradigms of stimulation will have a lower impact on cognitive function than current settings
of stimulation.To date, current DBS settings are continuous. That is, stimulation runs at
approximately 200 pulses per second, all day long, day and night.
The novel settings that investigators will study are part of a translational pipeline at
Cleveland Clinic. Dr. Ken Baker and Dr. Machado are partners in the lab and in clinical
research. Dr. Baker has completed preclinical research that has shown that it is possible to
achieve excellent relief of parkinsonian symptoms with intermittent types of stimulation
known as coordinated reset. In other words, Dr Baker found that using a lower dose of
stimulation in an intermittent fashion can maintain the same level of symptom control.
Furthermore, a lower dose of stimulation could have less effects on cognitive symptoms.
In order to test these novel paradigms of stimulation, investigators will study patients
immediately after DBS and over time. The immediate research will be done starting on the
third day after implantation of the DBS lead(s), having the systems externalized for nine
days. The long-term research will be conducted with patients already fully implanted and
healed from surgery. In addition to evaluating for motor and cognitive tasks using computer
based assessments, investigators will utilize non-invasive electrophysiological measures
including EEG, EMG, MEG, and wearable accelerometer/gyroscopes to better characterize the
effects of stimulation settings.
Description:
The experimental design will include procedures to address each specific aim, with most
involving a within-subjects approach that examines the effect of different levels of
treatment (e.g., no therapy, traditional DBS, novel DBS) on neurological function, including
dependent variables derived from tests of motor and cognitive function. This approach will
extend to the electrophysiological data as well; where the relative effect of each level of
treatment on spontaneous- (e.g., resting beta and gamma band power) and task-related (i.e.,
evoked or event-related potential latency and amplitude characteristics) cerebral rhythms
will be quantified for each subject and further aggregated to characterize group-level
effects (see data analysis below).
Prior to surgery, participants will undergo additional brain imaging procedures in order to
characterize the anatomical and functional connectivity of the brain region to be targeted
during surgical lead placement and the cerebral cortex. The additional imaging sets will
include DTI and resting state functional MRI scans that will add an additional 30-45 minutes
to the standard of care pre-operative clinical MR procedure.
Following standard of care placement of the DBS lead(s) within the targeted brain region,
access to the lead for study-related activities will be achieved by attaching a disposable
extension to the end of the lead that is lodged subcutaneously, extracranially. The
disposable extension will then be tunneled to a site remote to that of the surgery in order
to minimize risk of contamination of the permanently implanted hardware. The recording
equipment will then be connected to the externalized extension, thus enabling study-related
DBS delivery and the recording of local field potentials (LFP) from the targeted brain
region.
Study-related activities will start the third morning after DBS surgery to allow the patient
time to recover from the implant procedure (start may be delayed if additional recovery is
deemed warranted through consultation with clinical care team). It is expected that the study
testing will continue through post-implant day 9, with the second standard of care DBS
implant surgery performed on post-implant day 10. During the externalization period, subjects
will participate in daily data collection tasks for up to 8 hours per day, with study-related
activities performed in short segments, broken up across morning and afternoon sessions. Once
testing is completed in the operationally-defined medication OFF state, patients will be
permitted to take their usual dose of medication and testing will continue. Frequent rest
periods will be included within each testing block to minimize fatigue effects and improve
data quality. Electrophysiological recordings may also be performed when the patient is not
in the laboratory, including overnight during sleep, using portable recording equipment and
activity monitors that resemble a holster device. Recordings will be made using either a
commercially-available cap electrode system that is placed temporarily during each
experimental session or using standard cup electrodes affixed to the scalp using either
standard methods (i.e., collodion or electrode paste). If collodion electrodes are used,
collodion electrodes will remain on the patient for several days in a row up to the duration
of the externalization period. Daily checks will be performed to ensure the integrity of the
electrode interface and electrodes will be re-gelled or re-applied as needed.
Daily study-related activities within the laboratory will include 1) spontaneous recordings
made with the patient at rest, 2) motor and cognitive task-synchronized recordings, and 3)
somatosensory evoked potentials, and 4) evoked potentials elicited by direct stimulation of
the deep brain target region. On the first day of testing, a monopolar threshold review,
similar to what is performed as part of standard of care clinical DBS programming may be
performed. This involves careful titration of the settings of electrical stimulation
delivered via the DBS lead in order to determine thresholds for sensorimotor and other
side-effects and will help to set the upper limits of stimulation delivered as part of the
experimental procedures. Moreover, this process will be used to characterize the therapeutic
benefits derived from DBS. In all cases, stimulation will be limited to less than the
approved charge density safety limit of 30 microcoulombs/cm2 per phase. On certain days,
patients may be asked to arrive to the test location after an overnight fast from their
anti-PD medications in order to characterize the effect of dopaminergic medications on
experimental responses. Finally, daily schedules may be altered based upon patient fatigue as
well as potential scheduling conflicts (e.g., MRI or MEG availability) and the total number
of days the patient is externalized may be shortened at the discretion of the surgical team,
including the need to accommodate operating room scheduling.
A minimum of six months after surgery, participants will be asked to return for a follow-up,
approximately 4-hour research visit to evaluate therapeutic outcomes. Specifically, patients
will be asked to return to the main campus laboratory after an overnight fast from their
anti-parkinsonian medications. During that visit, the efficacy of the patient's
standard-of-care DBS programming settings (i.e., the settings set by their treating physician
as part of their routine, post-op clinical care) will be evaluated through blinded scoring
using subscales of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).
