Combined Theta-gamma STN Stimulation for Verbal Fluency in Parkinson Disease
NCT Number: NCT06509048
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Parkinson Disease
Interventions: OTHER: STN-DBS Theta Gamma Stimulation
Sponsor: University of Turin, Italy
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 15
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2023-11-10
Completion Date: 2024-12-30
Locations: AOU Città della Salute e della Scienza Torino, Torino, Italy

Summary:
Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) is an established, effective, and relatively safe therapeutic option for Parkinson's disease (PD) patients presenting levodopa-related motor complications despite the best medical therapy . Chronic high-frequency (130-180 Hz) stimulation is known to reduce motor fluctuations and dyskinesia, and to improve quality of life and several non-motor symptoms . However, current evidence suggests a long term decline of cognitive performance in PD patients with STN-DBS compared to those without DBS, especially executive function processes including verbal fluency.

Preliminary evidence from pilot studies suggested that low frequency theta oscillations (4-10 Hz) within the STN and correlated cortical networks are important in cognition, including verbal fluency, color-word interference, and spatial and episodic memory; cortical structures involved in category verbal fluency encompass not only the prefrontal cortex, but also the hippocampus and related medial temporal structures. There is also evidence that theta STN stimulations lead to a worsening of motor symptoms, compared with no stimulation and therapeutic stimulation (gamma frequency).

To date, new DBS systems allow the use of multiple current sources and/or frequency settings at different depths and directions in a single electrode, and then to combine different stimulation frequencies.

Considering this, the aim is to evaluate the use of combined high (gamma) and very low (theta) frequency stimulation in a randomized, cross-over, double-blind trial with this principal research questions:

1. Can combined theta-gamma theta frequency STN stimulation improve verbal fluency in PD patients?
2. Can combined theta-gamma frequency STN stimulation improve verbal frequency without worsening cardinal motor symptoms?

Primary Outcome Measures: Verbal Fluency - Phonemic Fluency, Number of words per three given letters in one minute for each letter, Baseline; 1st month; 2nd month|Verbal Fluency - Semantic Fluency - Episodic category, Number of words per episodic category (related to personal past experiences, e.g., "memorable events" or "significant places") in one minute, Baseline; 1st month; 2nd month|Verbal Fluency - Semantic Fluency - Non-episodic category, Number of words per non episodic category (belonging to a specific category, e.g., animals, fruits) in one minute, Baseline; 1st month; 2nd month|Verbal Fluency - Semantic Fluency - Switching, Number of words with switch of categories: participants are required to alternately generate words from two different non episodic categories (e.g., animals and fruits) in one minute, Baseline; 1st month; 2nd month|Motor symptoms, Movement Disorder Society - Unified Parkinson Disease Rating Scale part III (MDS-UPDRS III). Change in total MDS UPDRS part III score between standard and Theta-Gamma stimulation. Score range: 0-132 (higher score indicates worse motor performance), Baseline; 1st month; 2nd month