Clinical trial NCT04218526: Deep Brain Stimulation of the Cuneiform Nucleus for Levodopa-resistant Freezing of Gait in Parkinson's Disease
Official title: Deep Brain Stimulation of the Cuneiform Nucleus for Levodopa-resistant Freezing of Gait in Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson Disease
Lead sponsor: University of Miami
Sponsor class: OTHER
Collaborators: name: Boston Scientific Corporation
First posted: 2020-01-06
Enrollment: 5
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine if DBS is a safe and effective therapy for severe freezing of gait in patients with Parkinson's Disease. Freezing of gait (FOG) is a particularly debilitating motor deficit seen in a subset of patients with Parkinson's Disease (PD).


Eligibility criteria: Inclusion:

1. Confirmed Parkinson's Disease according to movement disorder neurologist with documented exclusion of other disorders such as fronto-temporal dementia (FTD)/ frontal gait disorder/normal pressure hydrocephalus (NPH)/progressive supranuclear palsy (PSP)
2. PD stage3 ON medication, with severe gait dysfunction and predominant axial symptoms: Movement Disorder Society-Unified Parkinson's Disease Rating Scale Tremor Dominant (MDS-UPDRS TD), Postural Instability Gait Difficulty (PIGD) ratio ≤ 0.90 and Freezing Of Gait Questionnaire (FOGQ) score \> 12.
3. Age 40-75 with good response to Levodopa (defined as greater than 20% improvement in UPDRS score)
4. FOG refractory to LEVODOPA\>600 mg
5. 6. Minimal tremor, bradykinesia, and rigidity symptoms, or well controlled with Levodopa and/or with already implanted STN/GPi DBS.
6. a) Poor candidate for STN or GPi DBS due to good control of tremor, bradykinesia, and rigidity symptoms with Levodopa b) or Post-operative STN/GPi DBS PD patients with significant residual non-levodopa responsive postural and gait instability
7. Must agree to full 6-month participation in study.

Exclusion:

1. Individuals with major executive dysfunction
2. Individuals with dementia, as defined by the Mattis Dementia Rating Scale-2 (DRS-2) score ≤ 130
3. Individuals with other neurocognitive impairments
4. Individuals who have depression, as defined for example by the Beck Depression Inventory II (BDI-II) \> 25
5. Presence of major medical co-morbidities and other surgical contra-indications such as coagulopathy
6. Individuals who require diathermy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT)
7. Individuals with a history of prior intracranial surgery
8. Individuals with a metallic implant in their head that is not MRI compatible (e.g., aneurysm clip, cochlear implant)
9. Individuals with active implantable devices anywhere in the body (e.g. cardiac pacemaker, defibrillator, spinal cord stimulator, implanted medication pump)
10. Individuals who are pregnancy or desire to become pregnant during the study
11. Individuals who are breastfeeding12.
12. Individuals who are on investigational drugs and any other intervention (not part of the guidelines for management of Parkinson's Disease) known to have a potential impact on outcome
13. Subjects utilizing recreational drugs at the time of screening will be excluded from the study with the exception of medicinal marijuana

Primary outcomes:
measure: Percent Change in Gait Velocity
timeFrame: Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op
measure: Percent change in UPDRS Part III on/off stimulation
timeFrame: Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op
Secondary outcomes:
measure: Percent Change in FOG Questionnaire
timeFrame: Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op
measure: Percent Change in PDQ 39
timeFrame: Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op
measure: Percent Change in PDQ-L
timeFrame: Baseline, 2 week, 6 weeks, 12 weeks, 24 weeks and 25-28 week post-op
measure: Percent Change in Muscle Amplitude
timeFrame: Baseline, 24 weeks
measure: Percent Change in number of Falls
timeFrame: Baseline, 24 weeks
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
Study officials:
affiliation: University of Miami
name: Jonathan R Jagid, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chang SJ, Cajigas I, Guest JD, Noga BR, Widerstrom-Noga E, Haq I, Fisher L, Luca CC, Jagid JR. MR Tractography-Based Targeting and Physiological Identification of the Cuneiform Nucleus for Directional DBS in a Parkinson's Disease Patient With Levodopa-Resistant Freezing of Gait. Front Hum Neurosci. 2021 Jun 8;15:676755. doi: 10.3389/fnhum.2021.676755. eCollection 2021.
citation: Chang SJ, Cajigas I, Guest JD, Noga BR, Widerstrom-Noga E, Haq I, Fisher L, Luca CC, Jagid JR. Deep brain stimulation of the Cuneiform nucleus for levodopa-resistant freezing of gait in Parkinson's disease: study protocol for a prospective, pilot trial. Pilot Feasibility Stud. 2021 Jun 2;7(1):117. doi: 10.1186/s40814-021-00855-7.