Dual Frequency Stimulation in Parkinson's Disease

Parkinson Disease Clinical Trial

Official title:

Dual Frequency, Dual Region Deep Brain Stimulation of the Subthalamic Nucleus in Parkinson's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04650932
• Other study ID #: 1633883
• Status: Recruiting
• Phase: N/A
• Start date: October 22, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: University of California, Davis
• Contact: Kiarash Shahlaie, MD, PhD
• Phone: 916-703-5505
• Email: krshahlaie[@]ucdavis.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Deep brain stimulation (DBS) in the dorsal region of the subthalamic nucleus (STN) is very effective for reducing motor symptoms of Parkinson's disease (PD). Modeling studies suggest that this therapy may result in current spread into the ventral STN, causing altered cognitive processes. As a result, current stimulation parameters often lead to worsening in verbal fluency, executive function, and, particularly, cognitive control. There is evidence suggesting that low frequency oscillatory activity occurs across brain circuits important in integrating information for cognition. Preclinical studies and human recording studies indicate these low frequency theta oscillations drive cognitive control during cognitive tasks. Thus, the purpose of this study is to determine the safety, tolerability, and efficacy of low frequency stimulation (LFS) of the ventral STN alongside standard high frequency stimulation (HFS) of the dorsal STN in patients with PD.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Individuals who are 18 years and older

• Individuals with idiopathic Parkinson's Disease who previously underwent implantation with the Boston Scientific VerciseTM DBS system

• Individuals who have been implanted with the Boston Scientific VerciseTM DBS system for at least 3 months

• Individuals diagnosed with advanced PD who had bilateral dorsal subthalamic nucleus DBS surgery, as standard of care for motor improvement, with distal contacts of the electrodes implanted into the ventral STN

Exclusion Criteria:

• Individuals unable to provide consent and/or lack capacity to consent

• Individuals diagnosed with any cognitive or physical impairments that would limit their ability to participate in the cognitive testing

• Individuals who score below 15 on the Montreal Cognitive Assessment Test-Blind

• Individuals who score above 20 on the Center for Epidemiologic Studies Depression Scale

• Pregnant women (note: pregnant women are not candidates for DBS surgery), and prisoners

• Non-English speaking individuals. Cognitive tasks will only be conducted in English.

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Device:
• Deep brain stimulation
Patients with idiopathic Parkinson's disease who have previously been implanted with the Boston Scientific VerciseTM DBS system for at least 3 months. These patients will already be receiving high-frequency dorsal STN stimulation as part of the standard of care for PD. Once patients have provided consent and are enrolled in this study, they will receive simultaneous low-frequency stimulation of the ventral STN to examine if there are any effects on cognitive performance.

Locations

Country	Name	City	State
United States	UC Davis Health	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

References & Publications (26)

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Izadi A, Pevzner A, Lee DJ, Ekstrom AD, Shahlaie K, Gurkoff GG. Medial septal stimulation increases seizure threshold and improves cognition in epileptic rats. Brain Stimul. 2019 May-Jun;12(3):735-742. doi: 10.1016/j.brs.2019.01.005. Epub 2019 Jan 17. — View Citation

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Lee DJ, Gurkoff GG, Izadi A, Seidl SE, Echeverri A, Melnik M, Berman RF, Ekstrom AD, Muizelaar JP, Lyeth BG, Shahlaie K. Septohippocampal Neuromodulation Improves Cognition after Traumatic Brain Injury. J Neurotrauma. 2015 Nov 15;32(22):1822-32. doi: 10.1 — View Citation

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* Note: There are 26 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change from Baseline in Depression Scores on the Center for Epidemiologic Studies Depression Scale (CES-D)	The score of the CES-D will be compared across sessions and a score that rises above 20 (out of 60) will be considered positive for the development of depression.	Baseline, Week 2, Week 6, Month 3, and Month 6
Primary	Mean Change from Baseline in Impulsiveness Scores on the Barratt Impulsiveness Scale (BIS-11)	The score of the BIS-11 will be evaluated across sessions and elevated scores indicate greater impulsivity and risk-taking behavior. The scale involves 30 questions with values from 1-4. Overall scores range from 30-120.	Baseline, Week 2, Week 6, Month 3, and Month 6
Primary	Mean Change from Baseline in Neuropsychiatric Inventory (NPI)	The NPI assesses frequency, change in severity, and distress over 12 neuropsychiatric domains as evaluated by the caregiver. We will look for a significant score reduction in any domain of the NPI.	Baseline, Week 2, Week 6, Month 3, and Month 6
Primary	Mean Change from Baseline in Movement Scores on Part III of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Part III of the MDS-UPDRS consists of 18 areas of motor assessments to assess severity of symptoms. Each score is rated in terms of severity from 0-4, with higher scores indicating higher severity of symptoms. A composite score will be evaluated for changes from baseline.	Baseline, Week 2, Week 6, Month 3, and Month 6
Primary	Mean Change from Baseline in Cognitive Performance Scores on the Montreal Cognitive Assessment - Blind (MoCA)	This will be collected via telephone calls. The MoCA-Blind has been validated for telephone administration. We will re-evaluate MoCA-Blind scores during telephone monitoring to assess any changes to cognitive ability. A total score of less than 15 out of a possible 22 indicates greater than mild cognitive impairment.	Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5
Primary	Mean Change from Baseline in Depression Scores on the CES-D Short Version (CES-D-R10)	This will be collected via telephone calls. Patients will be given an unmarked form with questions and will be able to follow along the telephone conversation and answer each question (0-4 severity rating scale) for 10 questions focused on patient affect. A total score greater than 10 (out of 30) indicates the development of depression symptoms.	Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5
Primary	Mean Change from Baseline in Motor and Non-Motor Aspects of Daily Living Scores on Parts I and II of the MDS-UPDRS	This will be collected via telephone calls. Patients will be asked questions relating to motor and non-motor aspects of daily living and to rate the severity of their symptoms on a scale from 0-4, with higher scores indicating higher severity of symptoms. We will assess for changes in the composite score from baseline.	Baseline, Hour 24, Week 1, Month 1, Month 2, Month 4, and Month 5
Secondary	Mean Change from Baseline in Decision-Making Scores on Probabilistic Gambling Task	A patient-specific measure of risk attitude during a gambling task. We will estimate indifference points (win probability at which risky choice is chosen 50% of the time) at each time point and compare to those points during baseline performance on the task.	Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6
Secondary	Mean Change from Baseline in Inter-Temporal Choice Scores on a Temporal Discounting Task	A patient-specific measure of risk attitude during a temporal preferences task. We will examine the area under the curve of the empirical discount functions of 'larger later' rewards and 'smaller sooner' rewards. Smaller values indicate increased preference for smaller sooner over larger later rewards. Scores will be compared to baseline performance on the task.	Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6
Secondary	Mean Change from Baseline in Verbal Fluency Scores on Word Generation Task	The average number of words generated in a 1-minute time frame.	Baseline, Minute 30, Week 2, Week 6, Month 3, and Month 6