Clinical trial NCT06618157: Connectomic Guided DBS for Parkinson's Disease
Official title: Connectomic Guided Deep Brain Stimulation (DBS) for Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Parkinson Disease
Tremor
Dyskinesias
Keywords: DBS
Parkinson's disease
Connectomic
Tremor
Dyskinesia
Wearable
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Two alternative deep brain stimulation (DBS) stimulation plans will be created by maximizing the stimulation to the cerebellothalamic tract (1) and to the pallidothalamic tract (2) based on the patient-specific connectomic DBS model previously created with recruitment curves. Participants will be asked to attend one single research encounter for DBS programming, MDS-UPDRS scoring and wearable data collection. During their research visit, MDS-UPDRS III (clinical scale) and wearable data will be collected in different scenarios (each setting will be recorded for 20 minutes):

* "OFF" oral dopaminergic medication: during no DBS stimulation, usual care stimulation, cerebellothalamic optimized, and pallidothalamic optimized. This will be collected during the morning.
* "ON" oral dopaminergic medication: during no DBS stimulation, usual care stimulation, cerebellothalamic optimized, and pallidothalamic optimized
Primary purpose: TREATMENT

Brief summary: The objective of this research is to use advanced connectomic imaging models to identify disease-relevant axonal pathway targets for better tremor control in Parkinson's disease patients while avoiding undesirable side effects, with the goal of increasing precision and facilitating the choice of optimal DBS parameters for certain disease phenotypes. The investigators hypothesize that patient centered subthalamic nucleus deep brain stimulation of cerebellothalamic axonal pathways and pallidothalamic tract activation can provide better tremor control while avoiding worsening dyskinesias in patients with Parkinson's disease with significant tremor.

Detailed description: Patients with Parkinson's disease (PD) can suffer from significant disability due to tremors, rigidity, bradykinesia, or motor fluctuations, in addition to non-motor symptoms of the disease. Deep brain stimulation (DBS) is the main surgical approach approved by the US Food and Drug Administration (FDA) for the treatment of medication-refractory PD. Despite recent advances, the selection of DBS parameters is based on trial-and-error experimentation by specialists over the course of months. Better understanding of the optimal network targets for symptomatic control would allow for therapy improvement and simplify the DBS programming process, increase efficiency, and possibly increase access to care.

Most studies of structural connectivity in PD have focused on the analysis of the subthalamic nucleus (STN). Previous studies analyzing structural connectivity of STN DBS have shown that specific motor symptoms benefit from the activation of different networks. Several tracts such as the cerebellothalamic tract (CBT), pallidothalamic (PT) and corticospinal tract (CST) course through the STN and might be relevant for DBS targeting. For patients with essential tremor, stimulation of the CBT might provide better tremor control, but studies in PD are lacking.

The investigators will use connectomic models to better understand the mechanistic qualities of axonal pathways in the STN in Parkinson's disease and address the need for phenotype driven stimulation in PD. Estimating targeted axonal pathways by using connectomic models may guide personalized decision-making and targeting of DBS. It has the potential to improve clinical outcomes and reduce the number of visits needed for DBS optimization.

The study involves the extraction of data collected during routine clinical care, and data collected during the intervention study.

Data collected during routine clinical care includes:

* Demographic characteristics: age, gender, ethnicity, race.
* Clinical characteristics: disease duration, Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) prior to DBS implementation, levodopa equivalent daily dose of medications.
* Imaging data: DBS lead location, stimulation model activation pathway, recruitment curves, percent of each pathway activated with clinical DBS settings

Eligibility criteria: Inclusion Criteria:

* Age 18 or older
* Diagnosed with Parkinson's disease and has previously been implanted with bilateral subthalamic nucleus deep brain stimulation (DBS)
* Received DBS at least three months prior to the time of the study to allow for optimization of usual clinical care
* With at least mild tremor on a pre-operatory MDS-UPDRS clinical scale as defined by at least 2 out of 4 resting tremor grading on MDS-UPDRS on at least one extremity

Exclusion Criteria:

* Not having a post-operative head CT with 1mm or smaller axial slices at least 1 week after initial lead implantation.
* Patients who received DBS less than three months prior to the start of the study

Primary outcomes:
measure: Tremor duration as measured by wearables
timeFrame: Approximately eight hours
measure: Tremor severity as measured by wearables
timeFrame: Approximately eight hours
measure: Dyskinesia duration as measured by wearables
timeFrame: Approximately eight hours
measure: Dyskinesia severity as measured by wearables
timeFrame: Approximately eight hours
Secondary outcomes:
measure: Tremor severity as measured by the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS III)
timeFrame: Approximately eight hours
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Health Center at Morreene Road
state: North Carolina
Study officials:
affiliation: Duke University
name: Kyle Mitchell, MD
role: PRINCIPAL_INVESTIGATOR
References: