Mild DementiaNCT05910619
Transcranial Pulse Stimulation of the Brain
A study testing Neurolith Transcranial Pulse Stimulation Active in people with Mild Dementia and Aging Well, run by University of Florida at 1 site in United States.
Trial summary
This study will investigate transcranial pulse stimulation (TPS) as a method of enhancing cognitive and neural function. The study team will apply this low intensity, magnetically pulse technology to key brain regions in a randomized, sham-controlled trial (RCT). Read more about this study
- Who is it for?
- Ages 65 to 84 years
- Conditions the study is for
- Mild Dementia, Aging Well
- What is being tested?
- Neurolith Transcranial Pulse Stimulation Active
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Feb 2024to 7 May 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 65 to 84 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Men and women
- Age: 65 to 84 years
- English speaking
- Physically mobile with no history of balance difficulties or major falls
- For the typically-aging older adult group, phone screening performance on the TICS must be greater than or equal to 33 points, and cognitive performance of 26 points or greater on the MoCA and a Sum of Boxes score of 0 on the Clinical Dementia Rating scale administered to the participant's informant at the initial visit
- For the Mild dementia group, phone screening performance on the TICS must be between 21 and 32 points, and subsequent cognitive performance of on the MoCA must be <23 with a CDR Sum of Boxes score between 4.5 and 9.0 as administered to the participants known informant at the initial visit.
Who cannot join
- Neurological disorders unrelated to dementia / AD (e.g., Parkinson's disease, stroke, seizures, traumatic brain injury)
- Evidence of greater-than-mild dementia/AD (based on informant CDR Sum of Boxes score greater than 9.0 or MoCA <10)
- Past opportunistic brain infection
- Major psychiatric illness (schizophrenia, intractable affective disorder, current substance dependence diagnosis or severe major depression and/or suicidality) or any history of agitation and/or delirium
- Unstable (e.g., cancer other than basal cell skin) and chronic (e.g., diabetes mellitus) medical conditions
- MRI contraindications (e.g., pregnancy, claustrophobia, metal implants that are contraindicated for MRI and TPS)
Show all 13Show fewer
- Physical impairment precluding motor response or lying still for one hour and inability to walk two blocks without stopping or without balance difficulties
- Drug exclusions include those medications that are known to have cognitively sedating or altering effects as well medications with a strong anticholinergic burden or CNS effects. Participants should be stable on any recently altered medications/dosages for at least four weeks prior to beginning the study. Medications will be reviewed during the interview for the purpose of identification of contraindicated pharmacological agents with common cognitive side-effects
- Other history of medical conditions that may increase risk of cerebrovascular events, including prior heart attack, cardiac arrhythmia such as atrial fibrillation
- Hearing or vision deficits that will not allow for reliable standardized cognitive assessment; i.e. colorblindness, inability to hear through headphones (with or without hearing aids), macular degeneration or other significant diseases that cause severe loss of vision. If vision is corrected with lenses to appropriate levels, then participant will be eligible
- Left-handedness and ambidextrousness, as these individuals have a higher percentage rate of atypical functional lateralization for brain functions, which would significantly interfere with interpretability of brain data
- Hemophilia or other blood clotting disorders or thrombosis
- Corticosteroid treatment within the last six weeks before the first treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Florida
Gainesville, Florida, 32610
Joseph Gullett, Ph.D., 352-294-8631, gullettj@phhp.ufl.edu
Joseph M Gullett, PhD
About this study
Official title: Transcranial Pulse Stimulation of the Brain in Older Adults With and Without Mild Dementia
This study will investigate transcranial pulse stimulation (TPS) as a method of enhancing cognitive and neural function. The study team will apply this low intensity, magnetically pulse technology to key brain regions in a randomized, sham-controlled trial (RCT). The study will determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation among 10 typically-aging older adults and 10 patients with mild dementia.
Read the detailed description
The current study will investigate the use of the NEUROLITH TPS (transcranial pulse stimulation) generator device (Storz Medical AG, Tägerwilen, Switzerland) for enhancing cognitive and neural function in older adults with and without mild Alzheimer's disease (AD). This will be achieved by applying a novel, low intensity, magnetically pulsed technology to key brain regions and networks in a randomized, sham-controlled trial (RCT). The pilot RCT will be conducted to determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation using a 2x2 sham-controlled design in which 10 typically-aging older adults and 10 patients with mild AD will be randomized to receive either sham TPS or active TPS. All participants will undergo pre-intervention multi-modal MRI, blood draw, and neurocognitive evaluation followed by thrice-weekly TPS (sham or active) for two weeks total, followed by a post-intervention MRI, blood draw, and neurocognitive evaluation. The total duration of the study is expected to be around four weeks, where each participant will undergo a screening/eligibility visit, baseline visit with MRI and neurocognitive testing, 6 intervention visits, a post-intervention MRI and neurocognitive testing visit after the final stimulation session for a total of about 9 in-person visits. The final week of the study is a no-contact period in which the participant will be called approximately seven days after their final stimulation session to ensure no adverse events have occurred. The team will also contact participants quarterly for one year after the final session to complete a five minute phone survey.
The central hypothesis of this proposal is that TPS will increase cortical thickness, cerebral blood flow, neurite orientation and dispersion, and functional connectivity in targeted regions and their associated networks. Further, we hypothesize that these changes will translate to improvements in neurocognitive function more than that seen in the sham intervention, which is likely to occur due to practice effects alone.
The objectives of this study are to:
Aim 1. Determine whether application of TPS is associated with neurocognitive improvement H1.1. For both typically-aging older adults and patients with mild AD, active TPS will result in greater neurocognitive gains than sham TPS on a primary outcome measure of global cognition obtained from the ADAS-Cog-plus battery.
H1.2. Neurocognitive gains on the recall memory measures in active TPS will be greater for patients with mild AD compared to typically-aging older adults.
Aim 2. Determine whether TPS leads to improvements in functional (rsfMRI, ASL) and structural brain changes (NODDI).
H2.1. Active TPS targeting the AD-relevant regions and networks will potentiate increased connectivity in attention and working memory related (dorsolateral prefrontal cortex) brain systems, reflecting increased neural efficiency, while sham TPS will not.
H2.2. Active TPS will result in increased cerebral blood flow in targeted regions compared to sham TPS as measured by change in arterial spin labeling (ASL) metrics.
H2.3. White matter integrity will remain stable in the active TPS condition, with stable neurite density and neurite orientation dispersion occurring in targeted regions.
Aim 3. Evaluate which baseline neuroimaging characteristics best predict treatment response H3.1. In both typically aging older adults and mild AD, baseline within-network connectivity of the default mode network will be positively associated with change in a secondary outcome measure of executive function (NIH Examiner) for those randomized to active TPS, but not in sham TPS.
H3.2. In mild AD, average baseline neurite density within the white matter of the targeted regions will be positively associated with change in ADAS-Cog-plus total score after active TPS.
Exploratory Aim. Determine whether the intervention results in a clinically meaningful change in blood (plasma) based AD-related biomarkers.
- Conditions
- Mild Dementia, Aging Well
- Being tested
- Neurolith Transcranial Pulse Stimulation Active, Neurolith Transcranial Pulse Stimulation Sham
- Keywords
- Mild Dementia, Typical Aging, Transcranial Pulse Stimulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neurolith Transcranial Pulse Stimulation ActiveDevice
5hz (200-300 milliseconds) stimulation pulses transcranial pulse stimulation (TPS) will be applied to each of the following five regions twice per session in sequential order with the specified stimulation parameters: left dorsolateral prefrontal cortex and inferior frontal cortex extending to Broca's area (2x800 pulses), right dorsolateral prefrontal cortex and inferior frontal cortex extending to Broca's area (2x800 pulses; ROI volume ~136/164 cms), the left lateral parietal cortex extending to Wernicke's area (2x400 pulses; ROI volume ~122/147 cms), the right lateral parietal cortex extending to Wernicke's area (2x400 pulses; ROI volume ~122/147 cms), and the extended precuneus cortex (2x600 pulses; ROI volume 66/92 cms). With a repetition time of 5hz (0.00333 seconds) per pulse at a total of 6,000 pulses per participant, the duration of stimulation is about 20 minutes, not including transition time between ROI localization.
Neurolith Transcranial Pulse Stimulation ShamDevice
The intervention procedure described in the Active condition above will also be repeated in participants randomized to the Sham procedure, with the exception of the insertion of a lens over the device by the interventionist to prevent stimulation from reaching the brain.
| Study group | Role | What they receive |
|---|---|---|
| Active brain stimulation | Active comparator | These participants will receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description. Receives: Device: Neurolith Transcranial Pulse Stimulation Active |
| Sham brain stimulation | Sham comparator | These participants will also receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description, though the device will be set to "Sham" in a blinded fashion by the biostatistician by placing an air pouch in the device hand piece. Receives: Device: Neurolith Transcranial Pulse Stimulation Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
ADAS-Cog-Plus-EF&FA Battery Total Score
The ADAS-Cog-Plus total score is touted as the gold standard measure for outcomes measurement following anti-dementia interventions18, allows for reliable longitudinal data collection, and provides coverage of cognitive domains including orientation, memory, language, and praxis.
Measured: Four weeks
Secondary outcomes (1)
NIH Examiner Total Score
The Total Score from the NIH Examiner will provide coverage of frontal executive functions in a manner that could be completed in a short time frame to limit participant burden. The NIH Examiner was chosen as it 1) Can be completed in ~30 minutes; 2) Is computerized and well standardized with norms from a large national cohort of older adults; 3) Provides both accuracy and response time measures; 4) Emphasizes working memory and executive function domains of relevance to the study which are not fully assessed by the ADAS-cog-plus battery; and 5) Has been the subject of considerable focus and investment by NIA.
Measured: Four weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2023
- Study start16 Feb 2024
- Primary completion16 Mar 2027 (estimated)
- Study completion7 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mild DementiaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- 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
- Parallel groups
- Model description
- 2x2 sham-controlled design in which 10 typically-aging older adults and 10 patients with mild AD will be randomized to receive either sham TPS or active TPS
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Gullett, Ph.D., Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05910619
- Sponsor's protocol ID
- IRB202300156
- Status last verified
- Oct 2026
- First submitted
- 6 Jun 2023
- Last updated
- 6 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Pulse Stimulation of the Brain in Older Adults With and Without Mild Dementia
- ClinicalTrials.gov ID
- NCT05910619
- Acronym / sponsor ID
- IRB202300156
- Conditions
- Mild Dementia, Aging Well
- Keywords
- Mild Dementia, Typical Aging, Transcranial Pulse Stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- 16 Feb 2024 (actual)
- Primary completion
- 16 Mar 2027 (estimated)
- Study completion
- 7 May 2027 (estimated)
- First posted
- 20 Jun 2023 (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.
This study will investigate transcranial pulse stimulation (TPS) as a method of enhancing cognitive and neural function. The study team will apply this low intensity, magnetically pulse technology to key brain regions in a randomized, sham-controlled trial (RCT). The study will determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation among 10 typically-aging older adults and 10 patients with mild dementia.
Detailed description
The current study will investigate the use of the NEUROLITH TPS (transcranial pulse stimulation) generator device (Storz Medical AG, Tägerwilen, Switzerland) for enhancing cognitive and neural function in older adults with and without mild Alzheimer's disease (AD). This will be achieved by applying a novel, low intensity, magnetically pulsed technology to key brain regions and networks in a randomized, sham-controlled trial (RCT). The pilot RCT will be conducted to determine the magnitude of changes in cognitive function and brain function and structure between a pre- and post-stimulation using a 2x2 sham-controlled design in which 10 typically-aging older adults and 10 patients with mild AD will be randomized to receive either sham TPS or active TPS. All participants will undergo pre-intervention multi-modal MRI, blood draw, and neurocognitive evaluation followed by thrice-weekly TPS (sham or active) for two weeks total, followed by a post-intervention MRI, blood draw, and neurocognitive evaluation. The total duration of the study is expected to be around four weeks, where each participant will undergo a screening/eligibility visit, baseline visit with MRI and neurocognitive testing, 6 intervention visits, a post-intervention MRI and neurocognitive testing visit after the final stimulation session for a total of about 9 in-person visits. The final week of the study is a no-contact period in which the participant will be called approximately seven days after their final stimulation session to ensure no adverse events have occurred. The team will also contact participants quarterly for one year after the final session to complete a five minute phone survey.
The central hypothesis of this proposal is that TPS will increase cortical thickness, cerebral blood flow, neurite orientation and dispersion, and functional connectivity in targeted regions and their associated networks. Further, we hypothesize that these changes will translate to improvements in neurocognitive function more than that seen in the sham intervention, which is likely to occur due to practice effects alone.
The objectives of this study are to:
Aim 1. Determine whether application of TPS is associated with neurocognitive improvement H1.1. For both typically-aging older adults and patients with mild AD, active TPS will result in greater neurocognitive gains than sham TPS on a primary outcome measure of global cognition obtained from the ADAS-Cog-plus battery.
H1.2. Neurocognitive gains on the recall memory measures in active TPS will be greater for patients with mild AD compared to typically-aging older adults.
Aim 2. Determine whether TPS leads to improvements in functional (rsfMRI, ASL) and structural brain changes (NODDI).
H2.1. Active TPS targeting the AD-relevant regions and networks will potentiate increased connectivity in attention and working memory related (dorsolateral prefrontal cortex) brain systems, reflecting increased neural efficiency, while sham TPS will not.
H2.2. Active TPS will result in increased cerebral blood flow in targeted regions compared to sham TPS as measured by change in arterial spin labeling (ASL) metrics.
H2.3. White matter integrity will remain stable in the active TPS condition, with stable neurite density and neurite orientation dispersion occurring in targeted regions.
Aim 3. Evaluate which baseline neuroimaging characteristics best predict treatment response H3.1. In both typically aging older adults and mild AD, baseline within-network connectivity of the default mode network will be positively associated with change in a secondary outcome measure of executive function (NIH Examiner) for those randomized to active TPS, but not in sham TPS.
H3.2. In mild AD, average baseline neurite density within the white matter of the targeted regions will be positively associated with change in ADAS-Cog-plus total score after active TPS.
Exploratory Aim. Determine whether the intervention results in a clinically meaningful change in blood (plasma) based AD-related biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2x2 sham-controlled design in which 10 typically-aging older adults and 10 patients with mild AD will be randomized to receive either sham TPS or active TPS
| Arm | Type | Receives |
|---|---|---|
| Active brain stimulation | Active comparator | Device: Neurolith Transcranial Pulse Stimulation ActiveThese participants will receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description. |
| Sham brain stimulation | Sham comparator | Device: Neurolith Transcranial Pulse Stimulation ShamThese participants will also receive focused TPS (pulsed stimulation) of the specified default mode network regions as specified in the detailed study description, though the device will be set to "Sham" in a blinded fashion by the biostatistician by placing an air pouch in the device hand piece. |
Who may qualify
- Ages
- 65 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- Men and women
- Age: 65 to 84 years
- English speaking
- Physically mobile with no history of balance difficulties or major falls
- For the typically-aging older adult group, phone screening performance on the TICS must be greater than or equal to 33 points, and cognitive performance of 26 points or greater on the MoCA and a Sum of Boxes score of 0 on the Clinical Dementia Rating scale administered to the participant's informant at the initial visit
Key exclusion criteria (13 listed)
- Neurological disorders unrelated to dementia / AD (e.g., Parkinson's disease, stroke, seizures, traumatic brain injury)
- Evidence of greater-than-mild dementia/AD (based on informant CDR Sum of Boxes score greater than 9.0 or MoCA <10)
- Past opportunistic brain infection
- Major psychiatric illness (schizophrenia, intractable affective disorder, current substance dependence diagnosis or severe major depression and/or suicidality) or any history of agitation and/or delirium
- Unstable (e.g., cancer other than basal cell skin) and chronic (e.g., diabetes mellitus) medical conditions
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 |
|---|---|---|
| Neurolith Transcranial Pulse Stimulation Active5hz (200-300 milliseconds) stimulation pulses transcranial pulse stimulation (TPS) will be applied to each of the following five regions twice per session in sequential order with the specified stimulation parameters: left dorsolateral prefrontal cortex and inferior frontal cortex extending to Broca's area (2x800 pulses), right dorsolateral prefrontal cortex and inferior frontal cortex extending to Broca's area (2x800 pulses; ROI volume ~136/164 cms), the left lateral parietal cortex extending to Wernicke's area (2x400 pulses; ROI volume ~122/147 cms), the right lateral parietal cortex extending to Wernicke's area (2x400 pulses; ROI volume ~122/147 cms), and the extended precuneus cortex (2x600 pulses; ROI volume 66/92 cms). With a repetition time of 5hz (0.00333 seconds) per pulse at a total of 6,000 pulses per participant, the duration of stimulation is about 20 minutes, not including transition time between ROI localization. | Device | Active brain stimulation |
| Neurolith Transcranial Pulse Stimulation ShamThe intervention procedure described in the Active condition above will also be repeated in participants randomized to the Sham procedure, with the exception of the insertion of a lens over the device by the interventionist to prevent stimulation from reaching the brain. | Device | Sham brain stimulation |
Primary outcome
ADAS-Cog-Plus-EF&FA Battery Total Score
Time frame: Four weeks
The ADAS-Cog-Plus total score is touted as the gold standard measure for outcomes measurement following anti-dementia interventions18, allows for reliable longitudinal data collection, and provides coverage of cognitive domains including orientation, memory, language, and praxis.
1 secondary outcome
NIH Examiner Total Score
Time frame: Four weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- 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.
Joseph Gullett, Ph.D. principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Neurolith Transcranial Pulse Stimulation Active in people with Mild Dementia and Aging Well, run by University of Florida at 1 site in United States.
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 6 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 6 Oct 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joseph M Gullett, Ph.D. (352-294-8631, gullettj@phhp.ufl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ADAS-Cog-Plus-EF&FA Battery Total Score (time frame: Four weeks). 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 Oct 2026.