Parkinson DiseaseNCT06509048
Combined Theta-gamma STN Stimulation for Verbal Fluency in Parkinson Disease
A study testing STN-DBS Theta Gamma Stimulation in people with Parkinson Disease, run by University of Turin, Italy at 1 site in Italy.
Trial 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 . Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- STN-DBS Theta Gamma Stimulation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteItaly
- Study dates
- 10 Nov 2023to 30 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- History of dementia (MMSE ≤ 25),
- Major substance abuse,
- Stimulation provided in the more ventral contact
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Combined Theta-gamma Frequency Subthalamic Nucleus Stimulation on Verbal Fluency in Parkinson Disease: a Randomized, Double-blind, Crossover Study
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).
Read more
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:
- Can combined theta-gamma theta frequency STN stimulation improve verbal fluency in PD patients?
- Can combined theta-gamma frequency STN stimulation improve verbal frequency without worsening cardinal motor symptoms?
Read the 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 Parkinson's 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.
- Conditions
- Parkinson Disease
- Being tested
- STN-DBS Theta Gamma Stimulation
- Keywords
- Deep brain stimulation, Verbal fluency, Parkinson's disease
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
STN-DBS Theta Gamma StimulationOther
Standard STN-DBS stimulation with addiction of bilateral theta frequency stimulation of ventral contacts
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: STN-DBS Theta Gamma Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Verbal Fluency - Phonemic Fluency
Number of words per three given letters in one minute for each letter
Measured: 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
Measured: 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
Measured: 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
Measured: 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)
Measured: Baseline; 1st month; 2nd month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2024
- Study start10 Nov 2023
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turin, Italy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maurizio Zibetti, University of Turin, Italy
- Investigators
- Maurizio Zibetti, Principal investigator, A.O.U. Città della Salute e della Scienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06509048
- Sponsor's protocol ID
- Theta-Gamma DBS
- Status last verified
- Dec 2024
- First submitted
- 3 Jul 2024
- Last updated
- 6 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Combined Theta-gamma Frequency Subthalamic Nucleus Stimulation on Verbal Fluency in Parkinson Disease: a Randomized, Double-blind, Crossover Study
- ClinicalTrials.gov ID
- NCT06509048
- Acronym / sponsor ID
- Theta-Gamma DBS
- Conditions
- Parkinson Disease
- Keywords
- Deep brain stimulation, Verbal fluency, Parkinson's disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of Turin, ItalyUniversity, hospital or other
- Study start
- 10 Nov 2023 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 19 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Can combined theta-gamma theta frequency STN stimulation improve verbal fluency in PD patients?
- 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 Parkinson's 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard Stimulation | No intervention | –Standard STN-DBS stimulation |
| Theta-Gamma Stimulation | Experimental | Other: STN-DBS Theta Gamma StimulationStandard STN-DBS stimulation with addiction of bilateral theta frequency stimulation of ventral contacts |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (3 listed)
- History of dementia (MMSE ≤ 25),
- Major substance abuse,
- Stimulation provided in the more ventral contact
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| STN-DBS Theta Gamma StimulationStandard STN-DBS stimulation with addiction of bilateral theta frequency stimulation of ventral contacts | Other | Theta-Gamma Stimulation |
Primary outcome
Verbal Fluency - Phonemic Fluency
Time frame: Baseline; 1st month; 2nd month
Number of words per three given letters in one minute for each letter
Verbal Fluency - Semantic Fluency - Episodic category
Time frame: Baseline; 1st month; 2nd month
Number of words per episodic category (related to personal past experiences, e.g., "memorable events" or "significant places") in one minute
Verbal Fluency - Semantic Fluency - Non-episodic category
Time frame: Baseline; 1st month; 2nd month
Number of words per non episodic category (belonging to a specific category, e.g., animals, fruits) in one minute
Verbal Fluency - Semantic Fluency - Switching
Time frame: Baseline; 1st month; 2nd month
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
Motor symptoms
Time frame: Baseline; 1st month; 2nd month
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maurizio Zibetti principal investigator
A.O.U. Città della Salute e della Scienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing STN-DBS Theta Gamma Stimulation in people with Parkinson Disease, run by University of Turin, Italy at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Verbal Fluency - Phonemic Fluency (time frame: Baseline; 1st month; 2nd month). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.