Combined Theta-gamma STN Stimulation for Verbal Fluency in Parkinson Disease

NCT06509048 | Completed

• 1 other identifier: Theta-Gamma DBS
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Conditions

Parkinson Disease

Keywords

Deep brain stimulation; Verbal fluency; Parkinson's disease

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (2)

Standard Stimulation

NO INTERVENTION

Standard STN-DBS stimulation

Theta-Gamma Stimulation

EXPERIMENTAL

Standard STN-DBS stimulation with addiction of bilateral theta frequency stimulation of ventral contacts

Other: STN-DBS Theta Gamma Stimulation

Interventions

STN-DBS Theta Gamma Stimulation OTHER

Standard STN-DBS stimulation with addiction of bilateral theta frequency stimulation of ventral contacts

Theta-Gamma Stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>18 years old,
• Optimized DBS therapy in the last month,
• Stable medication regimen in the last month
• Able to provide informed consent
• Fluent in Italian
• Able to complete cognitive testing
• Patients implanted with bilateral Vercise Cartesia™ Directional Leads in the STN connected to a Vercise™ or Vercise Gevia™ or Vercise Genus™ DBS system

You may not qualify if:

• History of dementia (MMSE ≤ 25),
• Major substance abuse,
• Stimulation provided in the more ventral contact

Sponsors & Collaborators

• University of Turin, Italy: lead

Study Sites (1)

AOU Città della Salute e della Scienza Torino

Torino, Italy

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Maurizio Zibetti

  AOU Città della Salute e della Scienza Torino

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 19, 2024
• Study Start: November 10, 2023
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)