Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06509048
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-07-03
Brief Title:
Combined Theta-gamma STN Stimulation for Verbal Fluency in Parkinson Disease
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Effect of Combined Theta-gamma Frequency Subthalamic Nucleus Stimulation on Verbal Fluency in Parkinson Disease a Randomized Double-blind Crossover Study
Status:
RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Deep Brain Stimulation DBS of the subthalamic nucleus STN is an established effective and relatively safe therapeutic option for Parkinsons 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 andor 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
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 andor 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
Detailed Description:
Each patient will receive two treatment periods each lasting one month in a randomized cross-over double-blind study design
Patients will be randomly assigned to one of two sequences Group 1 will receive standard DBS first followed by theta-gamma DBS while Group 2 will receive theta-gamma DBS first followed by standard DBS This design ensures that each patient serves as their own control thereby reducing variability and enhancing the accuracy of the findings A computer program will generate the randomization list
One investigator in charge of changing DBS parameter settings will be unblinded to stimulation parameters and aware of the randomization sequence The theta-gamma stimulation will be set maintaining the classical stimulation of the patient gamma frequency 100-180 Hz with bilateral addiction of a ventral contact for stimulation with theta frequency 4-10 Hz
Two investigators blinded to stimulation parameters and randomization sequence will conduct clinical and neuropsychological assessments
The unblinded investigator will decide on a possible switch to the next sequence if the symptoms will not be well tolerated by the patient In case of persistent worsening even after the second modification the patient will be dropped out from the study Dopaminergic therapy will be stable during the study course
The clinical and neuropsychological test battery will include motor state evaluated with the Movement Disorder Society - Unified Parkinson Disease Rating Scale MDS-UPDRS Cognitive screening test as per Mini Mental State Examination MMSE Beck Depression Inventory - Short Form BDI-SF Questionnaire for Impulsive-Compulsive Disorders in Parkinsons Disease-Rating Scale QUIP-RS Phonemic and semantic verbal fluency test letter episodic category non-episodic category and category switching
The neuropsychological test battery will be conducted at baseline and at the end of first and second month of evaluation The verbal fluency evaluation will be conducted also one hour after the change of stimulation parameters to also evaluate its impact at a short time distance
The evaluation will be conducted in the morning during the ON phase in order to avoid possible effects of wearing-off on cognitive performance
Patients will be randomly assigned to one of two sequences Group 1 will receive standard DBS first followed by theta-gamma DBS while Group 2 will receive theta-gamma DBS first followed by standard DBS This design ensures that each patient serves as their own control thereby reducing variability and enhancing the accuracy of the findings A computer program will generate the randomization list
One investigator in charge of changing DBS parameter settings will be unblinded to stimulation parameters and aware of the randomization sequence The theta-gamma stimulation will be set maintaining the classical stimulation of the patient gamma frequency 100-180 Hz with bilateral addiction of a ventral contact for stimulation with theta frequency 4-10 Hz
Two investigators blinded to stimulation parameters and randomization sequence will conduct clinical and neuropsychological assessments
The unblinded investigator will decide on a possible switch to the next sequence if the symptoms will not be well tolerated by the patient In case of persistent worsening even after the second modification the patient will be dropped out from the study Dopaminergic therapy will be stable during the study course
The clinical and neuropsychological test battery will include motor state evaluated with the Movement Disorder Society - Unified Parkinson Disease Rating Scale MDS-UPDRS Cognitive screening test as per Mini Mental State Examination MMSE Beck Depression Inventory - Short Form BDI-SF Questionnaire for Impulsive-Compulsive Disorders in Parkinsons Disease-Rating Scale QUIP-RS Phonemic and semantic verbal fluency test letter episodic category non-episodic category and category switching
The neuropsychological test battery will be conducted at baseline and at the end of first and second month of evaluation The verbal fluency evaluation will be conducted also one hour after the change of stimulation parameters to also evaluate its impact at a short time distance
The evaluation will be conducted in the morning during the ON phase in order to avoid possible effects of wearing-off on cognitive performance
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None