Lewy Body DiseaseSCANNCT04817891

Stimulation of Cingulo-opercular Alertness Network

A study testing HD-tDCS in people with Lewy Body Disease and Lewy Body Variant of Alzheimer Disease, run by University of Michigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 50 to 90 years
Conditions the study is for: Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Lewy Body Dementia With Behavioral Disturbance
What is being tested?: HD-tDCS
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: 1 siteUnited States
Study dates: 3 May 2021to 26 Aug 2024
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 50 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

LBD patients (DLB or PDD) who have cognitive fluctuations and who are on stable doses of cholinesterase inhibitors (i.e., at least 4 weeks) will be recruited to participate in this study.
DLB patients will meet the Fourth consensus report of the DLB Consortium inclusion criteria for probable DLB.
Subjects will be identified according to the following recognized DLB features: spontaneous parkinsonian motor signs, fluctuating attention and concentration, recurrent well-formed visual hallucinations, presence of REM behavioral sleep disturbance, anosmia/hyposmia,or autonomic dysfunction.
PDD patients will meet the criteria by Emre et al. (Cognitive deficits in at least two of four of the following cognitive domains: Impaired attention, impaired executive functions, impairment in visuo-spatial functions, impaired free recall memory typically improved with cuing. Must also meet criteria for at least one behavioral symptom: apathy, depressed or anxious mood, hallucinations, delusions, excessive daytime sleepiness). Lack of behavioral symptoms does not exclude the diagnosis. Must also have none of Group III features present: (1) Co-existence of any other abnormality which might cause impairment, but judged not to be the cause of dementia. (2) Time interval between development of motor and cognitive symptoms not known. Must also have none of Group IV symptoms present: (1) Cognitive and behavioral symptoms appear solely in the context of other conditions such as acute confusion caused by systemic diseases or abnormalities, drug intoxication, or major depression according to DSM IV. (2) Features compatible with Probable Vascular Dementia criteria accordingly to NINDS-AIREN.

Who cannot join

Subjects with contra-indications to MR imaging and/or tDCS, including pacemakers or claustrophobia
Evidence of large vessel stroke or mass lesion on MRI
Use of anti-cholinergic or neuroleptic drugs
Evidence of atypical parkinsonism on neurological exam
Major psychiatric illness, such as bipolar disorder
Neurological conditions such as epilepsy, stroke, multiple sclerosis, or moderate to severe brain injury

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Sensory impairments that significantly limit one's ability to see or hear
A significant history of recent alcohol or drug dependence
Previous major radiation exposure
Pregnancy

Trial locations and contacts

1 site in 1 country.

United States1 site

4250 Plymouth Road (University of Michigan)
Ann Arbor, Michigan, 48105

Other trials in United States

About this study

Official title: Cholinergic Functions and Modulation of the Cingulo-opercular Alertness Network in LBD

Fluctuations in alertness are very common in persons with Lewy body dementias and are a major source of disability. Changes in a chemical messenger molecule called acetylcholine within certain brain regions may play a role in these fluctuations. We propose to test this hypothesis and also determine whether a non-invasive way of stimulating affected brain regions may be of relevance for future management of these fluctuations.

Read the detailed description

The central premise of the research study was that cholinergic system changes in specific neural network regions underlie cognitive fluctuations in patients with LBD. The cingulo-opercular task control (COTC) neural network is believed to play a role in maintenance of alertness but this remains uncertain in LDB. This critical knowledge gap formed the basis of the study's first aim. The study proposed to use transcranial direct current stimulation (tDCS) to "excite" critical cholinergic denervation components of the COTC as an adjunct to cholinergic pharmacotherapy in a target engagement study. tDCS is an emerging non-invasive neurostimulation technology that may improve a range of neurological symptoms, including cognition. The study evaluated whether target engagement by tDCS excitation of cholinergic denervated COTC hubs may affect cognitive fluctuations in LBD subjects.

While the cingulo-opercular network was expected to be the primary site of cholinergic denervation based on preliminary evidence, and thus the focus of the stimulation intervention, the typical pattern of cholinergic denervation in our sample occurred at a temporal lobe region that is classified as a node of the ventral attention network in the Gordon atlas. Additional results from examining different networks have been added to reflect the unanticipated relocation of stimulation location.

Conditions: Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Lewy Body Dementia With Behavioral Disturbance
Being tested: HD-tDCS
Keywords: Lewy Body Dementia, Cognitive, Thinking, Cognition, Cognitive Rehabilitation, Brain Stimulation, Imaging, Lewy Body, Dementia
Medical subject headings: Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

HD-tDCSDevice
Participants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models.

Study groups in NCT04817891
Study group	Role	What they receive
Experimental: HD-tDCS	Experimental	Maximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models. Receives: Device: HD-tDCS

What is being measured

The primary outcome is the main question the study is designed to answer.

Dementia Cognitive Fluctuations Scale
Score on a 4-item subscale of the 17-item Dementia Cognitive Fluctuation Scale (DCFS), developed to address limitations in prior scales and has good test-retest and inter-rater reliability; this subscale highly discriminates between dementia with Lewy bodies (DLB) and other dementia groups. The DCFS is a subjective report of cognitive fluctuation, the spontaneous change in cognitive ability which is a core diagnostic feature of DLB. Total subscale scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations. A decrease in score between Baseline and Post-Testing indicates an improvement in cognitive fluctuation.
Measured: Baseline and Post-Testing (3-4 weeks)

Secondary outcomes (3)

Resting State fMRI
Functional connectivity measures whether activity in different brain regions show similar patterns of change over time. Graph theory metrics of resting-state fMRI can characterize functional connectivity among nodes (regions) of a brain network, and well as between nodes of different brain networks. Network segregation is the difference of within-network and between-network connectivity as a proportion of within-network connectivity, such that higher numbers reflect more segregation. Given that network segregation typically decreases with normal and pathological aging, higher network segregation is generally considered cognitively beneficial.
Network segregation was examined for the ventral attention network (the actual focus of stimulation based on observed cholinergic denervation) and the original cingulo-opercular network, which was predicted at the time of grant proposal (but not supported by the observed cholinergic denervation).
Measured: Baseline and Post-Testing (3-4 weeks)
Stroop Color Word Interference Test - Cognitive Control Performance
Outcome Measure Description: Interference score in time to complete the Color Word Interference Test version of the Stroop task from the Delis-Kaplan Executive Function System. Participants 1) identify a series of colors, 2) read color words (e.g. blue) all written in black ink, and 3) name the ink color of color words printed in incongruous colored inks (e.g. for the word "green" written in red ink, the correct response is "red"). Tasks are performed as quickly as possible. Time to complete each task is recorded.
Interference score is calculated as the time to complete the color-word (interference) test (CWT), less the average of the time to complete the color task (CT) and word-reading task (WT): CWT - ((CT + WT)/2). The score has a theoretical valid range of 0 - 300; a lower score suggests better cognitive control. A negative change (decrease) in score between Baseline and Post-Testing indicates improvement in cognitive control performance.
Measured: Baseline, 3-4 weeks
Objective Measures of Working Memory (N-back Test)
The n-back test is a working memory task where a participant identify a stimulus that matches the stimulus experienced "n" steps back. Participants performed a 2-back test, in which they were asked to remember and press a button when presented with a stimulus that appeared two steps before the current one (e.g. square, circle, square).
The number of correct and incorrect identifications are normalized (z-score). Total score is the z-score of correct button presses minus the z-score of incorrect button presses. Possible scores range from -4.85 to 4.85.
A higher score (d') reflects better discrimination between target and non-target stimuli, and therefore better working memory performance. A positive change (increase) in 2-back score (d') between Baseline and Post-Testing indicates an improvement in working memory performance.
Measured: Baseline, 3-4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 May 202126 Aug 2024

First posted26 Mar 2021
Study start3 May 2021
Primary completion26 Aug 2024
Study completion26 Aug 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Lewy Body DiseaseStudies of the same condition, open and under way.
More trials run by University of MichiganThe 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: Not applicable
Intervention model: Single group
Model description: Eligible participants receive individualized intervention/stimulation based on their fMRI and PET imaging.
Masking: None (open label)
Enrolment: 15 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04817891
Sponsor's protocol ID: HUM00184296
Other IDs: R21AG069387
Acronym: SCAN
Status last verified: Oct 2025
First submitted: 23 Mar 2021
Last updated: 22 Oct 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
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 22 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Cholinergic Functions and Modulation of the Cingulo-opercular Alertness Network in LBD
ClinicalTrials.gov ID: NCT04817891
Acronym / sponsor ID: SCAN / HUM00184296
Conditions: Lewy Body Disease, Lewy Body Variant of Alzheimer Disease, Lewy Body Dementia With Behavioral Disturbance
Keywords: Lewy Body Dementia, Cognitive, Thinking, Cognition, Cognitive Rehabilitation, Brain Stimulation, Imaging, Lewy Body
Study type: Interventional
Recruitment status: Completed
Enrolment: 15 participants (actual)
Lead sponsor: University of MichiganUniversity, hospital or other
Collaborators: National Institute on Aging (NIA)
Study start: 3 May 2021 (actual)
Primary completion: 26 Aug 2024 (actual)
Study completion: 26 Aug 2024 (actual)
First posted: 26 Mar 2021 (actual)
Results: Posted 22 Oct 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Eligible participants receive individualized intervention/stimulation based on their fMRI and PET imaging.

Arm	Type	Receives
Experimental: HD-tDCS	Experimental	Device: HD-tDCSMaximum 4 milliAmp (mA) per channel of HD-tDCS treatment for 20 minutes, for 10 sessions. Total mA dose determined by individualized computational models.

Who may qualify

Ages: 50 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

LBD patients (DLB or PDD) who have cognitive fluctuations and who are on stable doses of cholinesterase inhibitors (i.e., at least 4 weeks) will be recruited to participate in this study.
DLB patients will meet the Fourth consensus report of the DLB Consortium inclusion criteria for probable DLB.
Subjects will be identified according to the following recognized DLB features: spontaneous parkinsonian motor signs, fluctuating attention and concentration, recurrent well-formed visual hallucinations, presence of REM behavioral sleep disturbance, anosmia/hyposmia,or autonomic dysfunction.
PDD patients will meet the criteria by Emre et al. (Cognitive deficits in at least two of four of the following cognitive domains: Impaired attention, impaired executive functions, impairment in visuo-spatial functions, impaired free recall memory typically improved with cuing. Must also meet criteria for at least one behavioral symptom: apathy, depressed or anxious mood, hallucinations, delusions, excessive daytime sleepiness). Lack of behavioral symptoms does not exclude the diagnosis. Must also have none of Group III features present: (1) Co-existence of any other abnormality which might cause impairment, but judged not to be the cause of dementia. (2) Time interval between development of motor and cognitive symptoms not known. Must also have none of Group IV symptoms present: (1) Cognitive and behavioral symptoms appear solely in the context of other conditions such as acute confusion caused by systemic diseases or abnormalities, drug intoxication, or major depression according to DSM IV. (2) Features compatible with Probable Vascular Dementia criteria accordingly to NINDS-AIREN.

Key exclusion criteria (10 listed)

Subjects with contra-indications to MR imaging and/or tDCS, including pacemakers or claustrophobia
Evidence of large vessel stroke or mass lesion on MRI
Use of anti-cholinergic or neuroleptic drugs
Evidence of atypical parkinsonism on neurological exam
Major psychiatric illness, such as bipolar disorder

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
HD-tDCSParticipants will receive HD-tDCS at up to 4 mA per channel for 20 minutes for 10 sessions. Dose determined through individualized computational models.	Device	Experimental: HD-tDCS

Primary outcome

Dementia Cognitive Fluctuations Scale
Time frame: Baseline and Post-Testing (3-4 weeks)
Score on a 4-item subscale of the 17-item Dementia Cognitive Fluctuation Scale (DCFS), developed to address limitations in prior scales and has good test-retest and inter-rater reliability; this subscale highly discriminates between dementia with Lewy bodies (DLB) and other dementia groups. The DCFS is a subjective report of cognitive fluctuation, the spontaneous change in cognitive ability which is a core diagnostic feature of DLB. Total subscale scores range from 4 to 20, with higher scores indicating greater cognitive fluctuations. A decrease in score between Baseline and Post-Testing indicates an improvement in cognitive fluctuation.

3 secondary outcomes

Resting State fMRI
Time frame: Baseline and Post-Testing (3-4 weeks)
Stroop Color Word Interference Test - Cognitive Control Performance
Time frame: Baseline, 3-4 weeks
Objective Measures of Working Memory (N-back Test)
Time frame: Baseline, 3-4 weeks

Results and safety

Results posted to the registry on 22 Oct 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Experimental: HD-tDCS	15	12

Primary outcome: Dementia Cognitive Fluctuations Scale

Time frame: Baseline and Post-Testing (3-4 weeks). Mean (Standard Deviation). Unit: score on a scale

Measure	Experimental: HD-tDCS n = 12
Baseline	11.75 (3.31)
Week 3/4	8.33 (1.56)

Experimental: HD-tDCS: p <0.001, t-test, 1 sided

Population analysed: Data is reported for participants who completed both baseline and week 3/4 measures.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: 4 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Experimental: HD-tDCS	0 of 13 (0%)	13 of 13 (100%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.

Benjamin Hampstead, PhD principal investigator

University of Michigan

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing HD-tDCS in people with Lewy Body Disease and Lewy Body Variant of Alzheimer Disease, run by University of Michigan 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 4 inclusion and 10 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 22 Oct 2025. 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. 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?

Yes. Results are posted in the registry (first posted 22 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Dementia Cognitive Fluctuations Scale (time frame: Baseline and Post-Testing (3-4 weeks)). 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 NCT04817891.

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 22 Oct 2025; AzTrials last refreshed its copy on 27 Oct 2026.