Clinical trial NCT03131817: Cortical Stimulation to Treat Mood and Behavioral Symptoms in Parkinson's Disease Patients
Official title: Cortical Stimulation to Treat Mood and Behavioral Symptoms in Parkinson's
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Parkinson's Disease
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2017-04-27
Enrollment: 10
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will investigate cortical stimulation to treat mood and behavioral symptoms in Parkinson's disease patients.

Detailed description: Depression, anxiety and impulse control disorders are among the most prominent neuropsychiatric symptoms in Parkinson's disease (PD) that greatly impact patients' and caregivers' quality of life. However, the neural correlate underlying these symptoms is still largely unknown preventing the development of comprehensive treatment for these symptoms.

The aims of this study are to 1) Determine the neural correlates of non-motor symptoms, 2) Determine how cortical stimulation can reduce these symptoms and normalize the abnormal brain signals, and 3) Teach patients how to voluntarily modulate the abnormal brain signals.

Ten PD patients undergoing deep brain surgery (DBS) implantation and diagnosed with mild to moderate mood disorder and/or impulsive behavior will be enrolled in this study. In addition to the standard therapeutic DBS electrode used to treat motor symptoms, a flexible electrode will be placed over the prefrontal cortex. Both electrodes will be attached to the Medtronic Activa PC+S pulse generator (and Medtronic Summit RC+S pulse generator as replacements), investigational devices that allows therapeutic stimulation and chronic brain recordings. At multiple time points, up to 2 years post-implantation, in our clinic or patient's home, brain signals will be recorded while patients are resting or performing emotion/cognition tasks. Symptoms will be assessed using validated questionnaires and tasks to allow identification of neurophysiological correlates of non-motor symptoms. There is also an optional sleep study included for better understanding of the brain's physiology. The investigators will then investigate the effect of cortical stimulation on both symptoms severity and brain signals that may be related to symptom expression. These signals will then be used to implement closed-loop controlled cortical stimulation and neuro-feedback controlled strategies.

Eligibility criteria: Inclusion Criteria:

* Ability to give informed consent for the study
* Age 30-75
* Diagnosis of Parkinson's disease by a movement disorders specialist
* Movement disorder symptoms that are sufficiently severe, in the setting of best medical therapy, to warrant surgical implantation of deep brain stimulators according to standard clinical criteria
* 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.

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 OR Patients intolerant to medication causing significant functional disability

* Have one or several mild to moderate mood or impulsive behavior as defined by:

  1. depression (BDI\>=13)
  2. anxiety (BAI \>=7)
  3. impulsive behavior as indicated by a positive score on the QUIP-A (Questionnaire for Impulsive-Compulsive disorders in Parkinson's Disease) or as determined by clinical interview or informant report
  4. Mood or behavior symptom fluctuations corresponding to minimum 30% improvement in non-motor symptoms when comparing visual analogue scales (VAS) scores in the on versus off medication state
* Stable doses of anti-Parkinsonian medications for at least 30 days prior to their baseline assessment.

Exclusion Criteria:

* Pregnancy or breast feeding
* MRI showing cortical atrophy out of proportion to age
* MRI showing focal brain lesions that could indicate a disorder other than idiopathic PD
* Major comorbidity increasing the risk of surgery (prior stroke, severe hypertension, severe diabetes, or need for chronic anticoagulation other than aspirin)
* Any prior intracranial surgery except DBS surgery
* Significant cognitive impairment (MoCA\<20).
* History of seizures
* Immunocompromised
* Has an active infection
* Requires diathermy, electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) to treat a chronic condition
* Inability to comply with study follow-up visits
* Any personality or mood symptoms that study personnel believe will interfere with study requirements.

Primary outcomes:
measure: Level of reduction in Anxiety in Parkinson's Disease patients treated with cortical stimulation
timeFrame: 24 months
measure: Level of reduction in Depression in Parkinson's Disease patients treated with cortical stimulation
timeFrame: 24 months
Secondary outcomes:
Other outcomes:
measure: Computational behavioral paradigms of reward processing
timeFrame: 48 months
measure: Neurofeedback testing using cortical and subcortical signals
timeFrame: 48 months
Locations:
city: San Francisco
country: United States
facility: UCSF Surgical Movement Disorders Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Simon Little, PhD
role: PRINCIPAL_INVESTIGATOR
References: