Clinical trial NCT02384421: Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
Official title: Adaptive Closed Loop Neuromodulation and Neural Signatures of Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Parkinson's Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2015-03-10
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: Continuous deep brain stimulation (cDBS) is an established therapy for the major motor signs in Parkinson's disease. Currently, cDBS is limited to "open-loop" stimulation, without real-time adjustment to the patient's state of activity, fluctuations and types of motor symptoms, medication dosages, or neural markers of the disease. The purpose of this study is to determine if an adaptive DBS system, responding to patient specific, clinically relevant neural or kinematic feedback, is efficacious on the motor Unified Parkinson's Disease Rating Scale (UPDRS III) and specific phenotypic measures in Parkinson's Disease compared to OFF therapy (i.e., OFF DBS and withdrawn from medication) and more efficient than cDBS. Not every recruited participant completed every part of the protocol.


Eligibility criteria: Inclusion Criteria:

1. A diagnosis of idiopathic Parkinson's disease, with bilateral symptoms at Hoehn and Yahr Stage greater than or equal to II.
2. Documented improvement in motor signs on versus off dopaminergic medication, with a change in the Unified Parkinson's Disease Rating Scale motor (UPDRS III) score of \>= 30% off to on medication.
3. The presence of complications of medication such as wearing off signs, fluctuating responses and/or dyskinesias, and/or medication refractory tremor, and/or impairment in the quality of life on or off medication due to these factors.
4. Subjects should be on stable doses of medications, which should remain unchanged until the DBS system is activated. After the DBS system is optimized (during which time the overall medication dose may be reduced to avoid discomfort and complications such as dyskinesias) the medication dose should remain unchanged, if possible, for the duration of the study.
5. Treatment with carbidopa/levodopa, and with a dopamine agonist at the maximal tolerated doses as determined by a movement disorders neurologist.
6. Ability and willingness to return for study visits, at the initial programming and after three, six and twelve months of DBS.
7. Age \> 18

Exclusion Criteria:

1. Subjects with significant cognitive impairment and/or dementia as determined by a standardized neuropsychological battery.
2. Subjects with clinically active depression, defined according to the Diagnostic and Statistical manual of Mental Disorders, Fourth Edition (DSM-IV) criteria and as scored on a validated depression assessment scale.
3. Subjects with very advanced Parkinson's disease, Hoehn and Yahr stage 5 on medication (non-ambulatory).
4. Age \> 80.
5. Subjects with an implanted electronic device such as a neurostimulator, cardiac pacemaker/defibrillator or medication pump.
6. Subjects, who are pregnant, are capable of becoming pregnant, or who are breast feeding.
7. Patients with cortical atrophy out of proportion to age or focal brain lesions that could indicate a non-idiopathic movement disorder as determined by MRI
8. Subjects having a major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin).
9. Subjects having any prior intracranial surgery.
10. Subjects with a history of seizures.
11. Subjects, who are immunocompromised.
12. Subjects with an active infection.
13. Subjects, who require diathermy, electroconvulsive therapy (ECT), or transcranial magnetic stimulation (TMS) to treat a chronic condition.
14. Subjects, who have an inability to comply with study follow-up visits.
15. Subjects, who are unable to understand or sign the informed consent

Primary outcomes:
measure: Normalized Beta Band Power (13-30 Hz) During aDBS
timeFrame: 30 minutes
measure: Change in UPDRS III Score
timeFrame: 30 minutes
Secondary outcomes:
measure: Disease Symptoms (Tremor)
timeFrame: 30 minutes
measure: Disease Symptoms (Freezing of Gait)
timeFrame: 30 minutes
measure: Disease Symptoms (Bradykinesia)
timeFrame: 30 minutes
measure: DBS Voltage
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Movement Disorders Center
state: California
Study officials:
affiliation: Stanford University
name: Helen Bronte-Stewart, MD MSE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimul. 2019 Jul-Aug;12(4):868-876. doi: 10.1016/j.brs.2019.02.020. Epub 2019 Feb 25.
citation: Malekmohammadi M, Herron J, Velisar A, Blumenfeld Z, Trager MH, Chizeck HJ, Bronte-Stewart H. Kinematic Adaptive Deep Brain Stimulation for Resting Tremor in Parkinson's Disease. Mov Disord. 2016 Mar;31(3):426-8. doi: 10.1002/mds.26482. Epub 2016 Jan 27. No abstract available.
citation: Petrucci MN, Neuville RS, Afzal MF, Velisar A, Anidi CM, Anderson RW, Parker JE, O'Day JJ, Wilkins KB, Bronte-Stewart HM. Neural closed-loop deep brain stimulation for freezing of gait. Brain Stimul. 2020 Sep-Oct;13(5):1320-1322. doi: 10.1016/j.brs.2020.06.018. Epub 2020 Jul 4. No abstract available.