Alzheimer DiseaseNCT06680154
Induction and Stabilization of Gamma Oscillations With 40 Hz External Brain Stimulation
A study testing Transcranial alternating current stimulation and Theta burst stimulation in people with Alzheimer Disease and Working Memory, run by The National Brain Mapping Laboratory (NBML) at 1 site in Germany.
Trial summary
The goal of the present studies is to develop and validate novel stimulation protocols for the entrainment of gamma oscillations, which are associated with many cognitive functions and critically involved in cognitive impairment such as Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Working Memory, EEG Brain Oscillations
- What is being tested?
- Transcranial alternating current stimulation and Theta burst stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 13 Jul 2021to 30 Nov 2023
- 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 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- normal or corrected to normal eye vision
- right-handed
- non-smokers
- being 18-60 years old
- providing written informed consent
Who cannot join
- history of neurological or psychiatric disorders including seizures or epilepsy,
- Taking CNS medication
- having metal implants
- current pregnancy
Trial locations and contacts
1 site in 1 country.
Germany1 site
Leibniz-Institut für Arbeitsforschung
Dortmund, North Rhine-Westphalia, 44139
About this study
Official title: Gamma Oscillations and Working Memory Following Combined 40Hz tACS and iTBS
The goal of the present studies is to develop and validate novel stimulation protocols for the entrainment of gamma oscillations, which are associated with many cognitive functions and critically involved in cognitive impairment such as Alzheimer's disease. In this proposal, combination of repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS), which has been shown effective for the induction, and stabilisation of alpha and theta frequencies in our forgoing studies, will be adopted to the gamma frequency range and applied on prefrontal regions as well as model-based cortical areas to enhance and stabilize gamma oscillations, thereby facilitating cognition
Read the detailed description
Neuropsychiatric disorders are a leading cause of global disability-adjusted life years, and treatment solutions are lacking. Recent findings suggest that non-invasive brain stimulation may be a valuable option in conditions such as epilepsy or Alzheimer's disease (AD). Still, a better understanding of mechanisms and patient-specific factors is needed. Personalized hybrid brain models uniting the physics of electromagnetism with physiology - NeuroTwins (NeTs) - are poised to play a fundamental role in understanding and optimizing the effects of stimulation at the individual level. The purpose of this project is to deliver solutions through model-driven, individualized therapy. A computational framework - weaved and validated across scales and levels of detail - will be proposed to represent the mechanisms of interaction of electric fields with brain networks and assimilate neuroimaging data. This will allow us to characterize the dynamical landscape of the individual brain and define strategies to restore healthy dynamics. The work package, which will take place at IfADo, is part of the consortium collaborating with labs across Europe and USA, aiming to validate and optimize the realistic hybrid brain models developed by NeTs. The targeted subject groups of the IfADo project will be healthy young and old participants. Non-invasive brain stimulation including repetitive transcranial magnetic stimulation and transcranial alternating current stimulation will be applied with electroencephalography, and magnetic resonance spectroscopy as outcome measures. The results are to be translated into a technology pipeline for the design of new personalized neuromodulation protocols which will further be tested in a cohort of AD patients by another clinical consortium member, delivering model-driven breakthroughs in basic and clinical neuroscience, with patients ultimately benefiting from safe, individualized therapy solutions.
- Conditions
- Alzheimer Disease, Working Memory, EEG Brain Oscillations
- Being tested
- Transcranial alternating current stimulation, Theta burst stimulation, Sham (No Treatment)
- Keywords
- Alzheimer's disease, Gamma oscillations, EEG, Transcranial alternating current stimulation, tACS, Intermittent theta burst stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial alternating current stimulationDevice
Transcranial alternating current was delivered utilizing a Starstim 8-channel constant current, battery-powered electric stimulator (Neuroelectrics, Barcelona, Spain). Circular carbon rubber electrodes (2cm radius, 12,57 cm2) were used throughout the stimulation. Before placing the electrodes on the head, the subject's hair was moved to the side
Theta burst stimulationDevice
the intermittent theta burst stimulation (iTBS) which is regarded as safe for high-frequency neuromodulation. Compared to classical rTMS, where pulses are applied repeatedly at a fixed frequency, iTBS consists of bursts of pulse triplets. In the classical protocol, the bursts are applied for two seconds in 5Hz intervals followed by an eight-second break, before the next bursts are applied. This pattern is repeated for 190 seconds resulting in 600 pulses per protocol.
Sham (No Treatment)Device
In the case of sham TMS, two different sham coils (double 70mm pCool-SHAM coil, Mag\&More GmbH, Munich, Germany) will produce audible clicks at the decibel intensity corresponding to an active coil without the induction of an electromagnetic pulse. Sham tACS will be applied by only ramping the current for 15 seconds up and 15 seconds down at the beginning and end of the stimulation respectively.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial alternating current stimulation | Active comparator | During tACS, an alternating electrical current with a 1 milliamp peak-to-peak amplitude will be delivered, featuring a 15-second ramp-up at the start and a 15-second ramp-down at the end. The stimulation duration is 20 minutes and four channels are used for delivering sinusoidal alternating currents to the head. The alternating current was delivered to the prefrontal cortex bilaterally with the electrodes at F3 and F4 and the return electrodes were placed at the ipsilateral mastoids at TP9 and TP10 (international 10-20 EEG electrode placement system). Receives: Device: Transcranial alternating current stimulation |
| intermittent theta burst stimulation | Active comparator | The intermittent theta burst stimulation (iTBS) is regarded as safe for high-frequency neuromodulation. The pulse bursts are applied for two seconds in 5Hz intervals followed by an eight-second break before the next bursts are applied. This pattern is repeated for 190 seconds resulting in 600 pulses per protocol. 80% of the individual subjects' active motor threshold (AMT) are used for stimulation intensity and will be applied four times within a 20-minute time frame starting at 0 minutes, 5 minutes, 10 minutes, and 15 minutes from the beginning of the intervention resulting in 2400 delivered pulses for the whole intervention Receives: Device: Theta burst stimulation |
| combited iTBS- tACS peak | Active comparator | To combine tACS and the iTBS protocol, a customized circuit is developed in-house to phase-lock the TMS pulses to the waveform generated by tACS. TMS pulses were delivered using two figure-of-eight shaped coils (double 70 mm, PMD coil type; Mag and More GmbH, Munich, Germany). For the stimulation, the center of the TMS coils are placed over the two prefrontal tACS electrodes (F3 and F4 electrode positions) with an orientation of 45 degrees to the midline and the handles pointing backward. Using the customized circuit, TMS pulses will be delivered at the peak of the tACS wave. Receives: Device: Transcranial alternating current stimulation; Device: Theta burst stimulation |
| Combined iTBS-tACS trough | Active comparator | To combine tACS and the iTBS protocol, a customized circuit is developed in-house to phase-lock the TMS pulses to the waveform generated by tACS. TMS pulses were delivered using two figure-of-eight shaped coils (double 70 mm, PMD coil type; Mag and More GmbH, Munich, Germany). For the stimulation, the center of the TMS coils are placed over the two prefrontal tACS electrodes (F3 and F4 electrode positions) with an orientation of 45 degrees to the midline and the handles pointing backward. Using the customized circuit, TMS pulses will be delivered at the trough of the tACS wave. Receives: Device: Transcranial alternating current stimulation; Device: Theta burst stimulation |
| sham | Sham comparator | 80% of the individual subjects' active motor threshold (AMT) four times within a 20-minute time frame starting at 0 minutes, 5 minutes, 10 minutes, and 15 minutes from the beginning of the intervention resulting in 2400 delivered pulses for the whole intervention Receives: Device: Sham (No Treatment) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Working Memory behavioral performance
Participants view a continuous sequence of alphabet letters, presented as stimuli in Arial font, size 120pt, on a tube screen positioned at 60cm eye distance. The stimuli are shown with a time interval of two seconds between them. The task consisted of six blocks with 70 stimuli, including 12 possible hit trials. Participants were instructed to press the left key on a response box if the presented stimulus matched either the one presented one trial prior (1-Back) or three trials prior (3-Back). In all other cases, participants press the right key. The left button is pressed with the index finger, while the right button is pressed with the middle finger of the right hand, with buttons aligned horizontally. The response condition varied by block, with three blocks for 3-Back and three for 1-Back, and the order was counterbalanced across participants and sessions.
Measured: During procedure (20 minutes)
electroencephalogram (EEG) oscillatory power
Change in the EEG power in alpha, delta, theta and beta bands
Measured: up to 2 hours after the intervention
electroencephalogram (EEG) functional connectivity
Change in EEG functional connectivity, specifically global efficiency, coherence, and phase-locking value.
Measured: up to 2 hours after the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2024
- Study start13 Jul 2021
- Primary completion30 Nov 2023
- Study completion30 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- The National Brain Mapping Laboratory (NBML)
- Sponsor type
- University, hospital or other
- Collaborators
- Leibniz Research Centre for Working Environment and Human Factors
- Responsible party
- Principal investigator, Mohammad Ali Salehinejad, Technical University of Dortmund
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06680154
- Sponsor's protocol ID
- IfADo_196
- Status last verified
- Mar 2026
- First submitted
- 5 Nov 2024
- Last updated
- 18 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Glinski B, Salehinejad MA, Takahashi K, Jamil A, Yavari F, Kuo MF, Nitsche MA. Phase-synchronized 40 Hz tACS and iTBS effects on gamma oscillations. Imaging Neurosci (Camb). 2025 Sep 10;3:IMAG.a.140. doi: 10.1162/IMAG.a.140. eCollection 2025.
PubMed 40948603
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gamma Oscillations and Working Memory Following Combined 40Hz tACS and iTBS
- ClinicalTrials.gov ID
- NCT06680154
- Acronym / sponsor ID
- IfADo_196
- Conditions
- Alzheimer Disease, Working Memory, EEG Brain Oscillations
- Keywords
- Alzheimer's disease, Gamma oscillations, EEG, Transcranial alternating current stimulation, tACS, Intermittent theta burst stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- The National Brain Mapping Laboratory (NBML)University, hospital or other
- Collaborators
- Leibniz Research Centre for Working Environment and Human Factors
- Study start
- 13 Jul 2021 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 8 Nov 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.
The goal of the present studies is to develop and validate novel stimulation protocols for the entrainment of gamma oscillations, which are associated with many cognitive functions and critically involved in cognitive impairment such as Alzheimer's disease. In this proposal, combination of repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS), which has been shown effective for the induction, and stabilisation of alpha and theta frequencies in our forgoing studies, will be adopted to the gamma frequency range and applied on prefrontal regions as well as model-based cortical areas to enhance and stabilize gamma oscillations, thereby facilitating cognition
Detailed description
Neuropsychiatric disorders are a leading cause of global disability-adjusted life years, and treatment solutions are lacking. Recent findings suggest that non-invasive brain stimulation may be a valuable option in conditions such as epilepsy or Alzheimer's disease (AD). Still, a better understanding of mechanisms and patient-specific factors is needed. Personalized hybrid brain models uniting the physics of electromagnetism with physiology - NeuroTwins (NeTs) - are poised to play a fundamental role in understanding and optimizing the effects of stimulation at the individual level. The purpose of this project is to deliver solutions through model-driven, individualized therapy. A computational framework - weaved and validated across scales and levels of detail - will be proposed to represent the mechanisms of interaction of electric fields with brain networks and assimilate neuroimaging data. This will allow us to characterize the dynamical landscape of the individual brain and define strategies to restore healthy dynamics. The work package, which will take place at IfADo, is part of the consortium collaborating with labs across Europe and USA, aiming to validate and optimize the realistic hybrid brain models developed by NeTs. The targeted subject groups of the IfADo project will be healthy young and old participants. Non-invasive brain stimulation including repetitive transcranial magnetic stimulation and transcranial alternating current stimulation will be applied with electroencephalography, and magnetic resonance spectroscopy as outcome measures. The results are to be translated into a technology pipeline for the design of new personalized neuromodulation protocols which will further be tested in a cohort of AD patients by another clinical consortium member, delivering model-driven breakthroughs in basic and clinical neuroscience, with patients ultimately benefiting from safe, individualized therapy solutions.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Transcranial alternating current stimulation | Active comparator | Device: Transcranial alternating current stimulationDuring tACS, an alternating electrical current with a 1 milliamp peak-to-peak amplitude will be delivered, featuring a 15-second ramp-up at the start and a 15-second ramp-down at the end. The stimulation duration is 20 minutes and four channels are used for delivering sinusoidal alternating currents to the head. The alternating current was delivered to the prefrontal cortex bilaterally with the electrodes at F3 and F4 and the return electrodes were placed at the ipsilateral mastoids at TP9 and TP10 (international 10-20 EEG electrode placement system). |
| intermittent theta burst stimulation | Active comparator | Device: Theta burst stimulationThe intermittent theta burst stimulation (iTBS) is regarded as safe for high-frequency neuromodulation. The pulse bursts are applied for two seconds in 5Hz intervals followed by an eight-second break before the next bursts are applied. This pattern is repeated for 190 seconds resulting in 600 pulses per protocol. 80% of the individual subjects' active motor threshold (AMT) are used for stimulation intensity and will be applied four times within a 20-minute time frame starting at 0 minutes, 5 minutes, 10 minutes, and 15 minutes from the beginning of the intervention resulting in 2400 delivered pulses for the whole intervention |
| combited iTBS- tACS peak | Active comparator | Device: Transcranial alternating current stimulation, Device: Theta burst stimulationTo combine tACS and the iTBS protocol, a customized circuit is developed in-house to phase-lock the TMS pulses to the waveform generated by tACS. TMS pulses were delivered using two figure-of-eight shaped coils (double 70 mm, PMD coil type; Mag and More GmbH, Munich, Germany). For the stimulation, the center of the TMS coils are placed over the two prefrontal tACS electrodes (F3 and F4 electrode positions) with an orientation of 45 degrees to the midline and the handles pointing backward. Using the customized circuit, TMS pulses will be delivered at the peak of the tACS wave. |
| Combined iTBS-tACS trough | Active comparator | Device: Transcranial alternating current stimulation, Device: Theta burst stimulationTo combine tACS and the iTBS protocol, a customized circuit is developed in-house to phase-lock the TMS pulses to the waveform generated by tACS. TMS pulses were delivered using two figure-of-eight shaped coils (double 70 mm, PMD coil type; Mag and More GmbH, Munich, Germany). For the stimulation, the center of the TMS coils are placed over the two prefrontal tACS electrodes (F3 and F4 electrode positions) with an orientation of 45 degrees to the midline and the handles pointing backward. Using the customized circuit, TMS pulses will be delivered at the trough of the tACS wave. |
| sham | Sham comparator | Device: Sham (No Treatment)80% of the individual subjects' active motor threshold (AMT) four times within a 20-minute time frame starting at 0 minutes, 5 minutes, 10 minutes, and 15 minutes from the beginning of the intervention resulting in 2400 delivered pulses for the whole intervention |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- normal or corrected to normal eye vision
- right-handed
- non-smokers
- being 18-60 years old
- providing written informed consent
Key exclusion criteria (4 listed)
- history of neurological or psychiatric disorders including seizures or epilepsy,
- Taking CNS medication
- having metal implants
- current pregnancy
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 |
|---|---|---|
| Transcranial alternating current stimulationTranscranial alternating current was delivered utilizing a Starstim 8-channel constant current, battery-powered electric stimulator (Neuroelectrics, Barcelona, Spain). Circular carbon rubber electrodes (2cm radius, 12,57 cm2) were used throughout the stimulation. Before placing the electrodes on the head, the subject's hair was moved to the side | Device | Combined iTBS-tACS trough, Transcranial alternating current stimulation, combited iTBS- tACS peak |
| Theta burst stimulationthe intermittent theta burst stimulation (iTBS) which is regarded as safe for high-frequency neuromodulation. Compared to classical rTMS, where pulses are applied repeatedly at a fixed frequency, iTBS consists of bursts of pulse triplets. In the classical protocol, the bursts are applied for two seconds in 5Hz intervals followed by an eight-second break, before the next bursts are applied. This pattern is repeated for 190 seconds resulting in 600 pulses per protocol. | Device | Combined iTBS-tACS trough, combited iTBS- tACS peak, intermittent theta burst stimulation |
| Sham (No Treatment)In the case of sham TMS, two different sham coils (double 70mm pCool-SHAM coil, Mag\&More GmbH, Munich, Germany) will produce audible clicks at the decibel intensity corresponding to an active coil without the induction of an electromagnetic pulse. Sham tACS will be applied by only ramping the current for 15 seconds up and 15 seconds down at the beginning and end of the stimulation respectively. | Device | sham |
Primary outcome
Working Memory behavioral performance
Time frame: During procedure (20 minutes)
Participants view a continuous sequence of alphabet letters, presented as stimuli in Arial font, size 120pt, on a tube screen positioned at 60cm eye distance. The stimuli are shown with a time interval of two seconds between them. The task consisted of six blocks with 70 stimuli, including 12 possible hit trials. Participants were instructed to press the left key on a response box if the presented stimulus matched either the one presented one trial prior (1-Back) or three trials prior (3-Back). In all other cases, participants press the right key. The left button is pressed with the index finger, while the right button is pressed with the middle finger of the right hand, with buttons aligned horizontally. The response condition varied by block, with three blocks for 3-Back and three for 1-Back, and the order was counterbalanced across participants and sessions.
electroencephalogram (EEG) oscillatory power
Time frame: up to 2 hours after the intervention
Change in the EEG power in alpha, delta, theta and beta bands
electroencephalogram (EEG) functional connectivity
Time frame: up to 2 hours after the intervention
Change in EEG functional connectivity, specifically global efficiency, coherence, and phase-locking value.
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 18 Mar 2026.
- Results publication: PubMed 40948603Glinski B, Salehinejad MA, Takahashi K, Jamil A, Yavari F, Kuo MF, Nitsche MA. Phase-synchronized 40 Hz tACS and iTBS effects on gamma oscillations. Imaging Neurosci (Camb). 2025 Sep 10;3:IMAG.a.140. doi: 10.1162/IMAG.a.140. eCollection 2025.
- Individual participant dataSharing planned: Undecided
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial alternating current stimulation and Theta burst stimulation in people with Alzheimer Disease and Working Memory, run by The National Brain Mapping Laboratory (NBML) at 1 site in Germany.
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 5 inclusion and 4 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 18 Mar 2026. 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 Germany. 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. Some participants in this study may receive a placebo. 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?
Working Memory behavioral performance (time frame: During procedure (20 minutes)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06680154, which also lists 1 linked publication.
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 18 Mar 2026.