Mild Cognitive ImpairmentNCT04099524
CogT BEEM Study (a tDCS Study)
A study testing tDCS in people with Mild Cognitive Impairment and Neuropsychiatric Syndrome, run by University of Rochester at 1 site in United States.
Trial summary
Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 60 to 90 years
- Conditions the study is for
- Mild Cognitive Impairment, Neuropsychiatric Syndrome
- What is being tested?
- tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2019to 19 Jan 2022
- 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 60 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Forty subjects with MCI and comorbid NPS, which have worsened in the past 2 years (as rated by their study-partner's responses to the NPI-Q):
- In the past month, presence of > 2 symptoms; and
- Compared to two years ago, having > 1 pre-exist symptom whose severity rating has worsened, or having > 1 new symptom; 2. Consensus diagnosis of "mild cognitive impairment due to Alzheimer's disease" based on 2011 NIA-AA diagnostic criteria by the investigators based on screening information: i. Memory deficits at screening: 1 standard deviation (SD) below age- and/or education- corrected population norms for the Rey Auditory Verbal Learning Test (RAVLT, Lists C\&D); ii. Global memory deficits at screening: Montreal Cognitive Assessment (MoCA, Version 2) total score within the range 18 ≤ x ≤ 26, after educational adjustment; iii. Preserved activity of daily living: ADL-PI-self total score ≤ 30; iv. Absence of dementia. 3. Stable (same dosage, frequency, type) on memory medications for ≥ 3 months before screening; 4. Stable (same dosage, frequency, type) on any anti-depressants, antipsychotics, and/or anxiolytics for ≥ 7 days; 5. Community-dwelling: Subjects live in homes or independent- and assisted- living facilities (i.e. - not nursing home residents, due to the large cognitive variability in nursing home residents); 6. Aged 60-89 years at screening; 7. English-speaking; 8. Adequate visual and hearing acuity for testing; 9. Verified tDCS and MRI safety: Subject should not have any contraindications to either and pass safety screening questions for both (see exclusion section for more information); 10. Capacity to consent, based on responses and ratings to the UCSD Brief Assessment of Capacity to Consent (UBACC) form modified for this study 11. Availability of a study partner who spends at least several hours per week with the subject, supervises his/her care, and who is willing to accompany the subject to some study visits and participate in the study; 12. Informed consent for study participation obtained by both the subject and his/her study partner; 13. Agree to donate 20mL of blood at baseline, after fasting for at least 8 hours (only water and prescribed medicines)
Who cannot join
- Participants may be excluded from enrollment, or have their enrollment deferred until they are eligible, for the reasons listed below. Final decisions regarding enrollment will be determined by the PI on a case-by-case basis.
- Presence of any neurological or vascular disorders (e.g. - Multiple Sclerosis [MS], Traumatic Brain Injury [TBI], chronic heart failure [CHF], Parkinson's disease [PD]);
- Clinical diagnosis of dementia as defined by the most recent version of the DSM;
- Current enrollment in another study aimed at improving cognitive abilities and/or emotional well-being;
- MRI contraindications (e.g. - pacemaker, implantable cardioverter defibrillator [ICD], aneurysm clips, severe claustrophobia);
- tDCS contraindications (e.g. - scalp or skin condition, history of migraines, seizures or epilepsy, and/or strokes, TBI), metallic implants, history of adverse effects to previous tDCS or other brain stimulation techniques).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effectiveness of a Non-Invasive, Low-Intensity Brain Stimulation Approach in Addressing Emotional Regulation
Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared neural circuit the investigators previously discovered and various NPS. The investigators will modify a key region within the NPS-shared neural circuit [i.e. left precentral gyrus (LPG), critical for regulating visual attention] with anodal transcranial direct current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial design the investigators will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which is considered the most detrimental type of NPS in MCI. The investigators will assign participants to 4-week active anodal vs. sham LPG online tDCS group. The investigators will assess resting-state and visual attention task-related functional MRI and informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS. Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.
- Being tested
- tDCS
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tDCSDevice
tDCS (LPG/C3-anode, orbitofrontal cortex/Fp2-cathode) will be administered for 4 weeks (1 session per weekday for 2 weeks, and then 2 sessions per week for 2 weeks, for a total of 14 sessions). All subjects will receive anodal tDCS stimulation for 20 minutes per session, on C3 and the cathode electrode on Fp2 using 10/20 EEG system. tDCS will be applied with a pair of 35 cm2 single-use sponges soaked in approximately 4mL of saline solution on each side (~8mL per sponge) connected to the stimulator. During the 20-minute tDCS session, we will use online tDCS design (i.e., a subject will simultaneously work on the visual attention-oriented task.
| Study group | Role | What they receive |
|---|---|---|
| active tDCS | Experimental | We will apply the stimulation for 20 minutes using current at 1.5mA with a ramp up and ramp down period of 30 seconds at the start and end of the session. Receives: Device: tDCS |
| sham tDCS | Sham comparator | tDCS will ramp up for 30 seconds with 1 mA current and then ramp off within 10 seconds. As 30 seconds is too short for tDCS to have any effects, this will be the control condition. tDCS is on for 30 seconds because that is usually the only time individuals would experience tingling and itching - a factor we aim to equate between experimental and control conditions. Receives: Device: tDCS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of C3 Activation (NPS-shared Neural Circuit Measure
Change of arbitrary unit LPG activation in response to visual attention task (measured using task related fMRI). No theoretical minimum or maximum exists for this scale.
Measured: from baseline to post-intervention (4 weeks)
Change of C3 Connectivity (NPS-shared Neural Circuit Measure 21)
Change of arbitrary unit of correlation between LPG and amygdala at rest (resting fMRI). No theoretical minimum or maximum exists for this scale.
Measured: from baseline to post-intervention (4 weeks)
Secondary outcomes (2)
Change of Patient-report NPS
Patient-reported NPS was measured using three mood-related questionnaires that probed mood within the past week: depression (Geriatric Depressive Scale ;GDS-30); anxiety (State-Trait-Anxiety-Inventory; STAI-state); and apathy (Apathy Evaluation Scale; AES). Total scores from individual measures were z-transformed (higher score indicating severer symptoms) across timepoints and averaged to create a composite mood score. A Z-score of 0 represents the population mean. Change of Z-score from baseline to post-intervention was used.
Measured: from baseline to post-intervention (4 weeks)
Change of Informant-rated NPS
Informant-reported NPS was measured using the 12-domain Neuropsychiatric Inventory (NPI-Full), including both frequency and severity (based on present symptoms) during the past week. We first calculated the frequency x severity for each domain, then averaged across domains, and finally adjusted for caregiving burden. Higher is worse. We calculated the change of the arbitrary score from baseline to post-intervention. No theoretical minimum and maximum scores exist
Measured: from baseline to post-intervention (4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2019
- Study start6 Dec 2019
- Primary completion19 Jan 2022
- Study completion19 Jan 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive ImpairmentStudies 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
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Vankee Lin, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04099524
- Sponsor's protocol ID
- STUDY00003664
- Other IDs
- R21MH120734
- Status last verified
- Nov 2023
- First submitted
- 19 Sep 2019
- Last updated
- 7 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Turnbull A, Anthony M, Tadin D, Porsteinsson AP, Heffner K, Lin FV. Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia. Cortex. 2023 Feb;159:131-141. doi: 10.1016/j.cortex.2022.10.015. Epub 2022 Dec 17.
PubMed 36623419
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of a Non-Invasive, Low-Intensity Brain Stimulation Approach in Addressing Emotional Regulation
- ClinicalTrials.gov ID
- NCT04099524
- Acronym / sponsor ID
- STUDY00003664
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 6 Dec 2019 (actual)
- Primary completion
- 19 Jan 2022 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 23 Sep 2019 (actual)
- Results
- Posted 7 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared neural circuit the investigators previously discovered and various NPS. The investigators will modify a key region within the NPS-shared neural circuit [i.e. left precentral gyrus (LPG), critical for regulating visual attention] with anodal transcranial direct current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial design the investigators will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which is considered the most detrimental type of NPS in MCI. The investigators will assign participants to 4-week active anodal vs. sham LPG online tDCS group. The investigators will assess resting-state and visual attention task-related functional MRI and informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS. Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active tDCS | Experimental | Device: tDCSWe will apply the stimulation for 20 minutes using current at 1.5mA with a ramp up and ramp down period of 30 seconds at the start and end of the session. |
| sham tDCS | Sham comparator | Device: tDCStDCS will ramp up for 30 seconds with 1 mA current and then ramp off within 10 seconds. As 30 seconds is too short for tDCS to have any effects, this will be the control condition. tDCS is on for 30 seconds because that is usually the only time individuals would experience tingling and itching - a factor we aim to equate between experimental and control conditions. |
Who may qualify
- Ages
- 60 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 1. Forty subjects with MCI and comorbid NPS, which have worsened in the past 2 years (as rated by their study-partner's responses to the NPI-Q):
- In the past month, presence of > 2 symptoms; and
- Compared to two years ago, having > 1 pre-exist symptom whose severity rating has worsened, or having > 1 new symptom; 2. Consensus diagnosis of "mild cognitive impairment due to Alzheimer's disease" based on 2011 NIA-AA diagnostic criteria by the investigators based on screening information: i. Memory deficits at screening: 1 standard deviation (SD) below age- and/or education- corrected population norms for the Rey Auditory Verbal Learning Test (RAVLT, Lists C\&D); ii. Global memory deficits at screening: Montreal Cognitive Assessment (MoCA, Version 2) total score within the range 18 ≤ x ≤ 26, after educational adjustment; iii. Preserved activity of daily living: ADL-PI-self total score ≤ 30; iv. Absence of dementia. 3. Stable (same dosage, frequency, type) on memory medications for ≥ 3 months before screening; 4. Stable (same dosage, frequency, type) on any anti-depressants, antipsychotics, and/or anxiolytics for ≥ 7 days; 5. Community-dwelling: Subjects live in homes or independent- and assisted- living facilities (i.e. - not nursing home residents, due to the large cognitive variability in nursing home residents); 6. Aged 60-89 years at screening; 7. English-speaking; 8. Adequate visual and hearing acuity for testing; 9. Verified tDCS and MRI safety: Subject should not have any contraindications to either and pass safety screening questions for both (see exclusion section for more information); 10. Capacity to consent, based on responses and ratings to the UCSD Brief Assessment of Capacity to Consent (UBACC) form modified for this study 11. Availability of a study partner who spends at least several hours per week with the subject, supervises his/her care, and who is willing to accompany the subject to some study visits and participate in the study; 12. Informed consent for study participation obtained by both the subject and his/her study partner; 13. Agree to donate 20mL of blood at baseline, after fasting for at least 8 hours (only water and prescribed medicines)
Key exclusion criteria (6 listed)
- Participants may be excluded from enrollment, or have their enrollment deferred until they are eligible, for the reasons listed below. Final decisions regarding enrollment will be determined by the PI on a case-by-case basis.
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 |
|---|---|---|
| tDCStDCS (LPG/C3-anode, orbitofrontal cortex/Fp2-cathode) will be administered for 4 weeks (1 session per weekday for 2 weeks, and then 2 sessions per week for 2 weeks, for a total of 14 sessions). All subjects will receive anodal tDCS stimulation for 20 minutes per session, on C3 and the cathode electrode on Fp2 using 10/20 EEG system. tDCS will be applied with a pair of 35 cm2 single-use sponges soaked in approximately 4mL of saline solution on each side (~8mL per sponge) connected to the stimulator. During the 20-minute tDCS session, we will use online tDCS design (i.e., a subject will simultaneously work on the visual attention-oriented task. | Device | active tDCS, sham tDCS |
Primary outcome
Change of C3 Activation (NPS-shared Neural Circuit Measure
Time frame: from baseline to post-intervention (4 weeks)
Change of arbitrary unit LPG activation in response to visual attention task (measured using task related fMRI). No theoretical minimum or maximum exists for this scale.
Change of C3 Connectivity (NPS-shared Neural Circuit Measure 21)
Time frame: from baseline to post-intervention (4 weeks)
Change of arbitrary unit of correlation between LPG and amygdala at rest (resting fMRI). No theoretical minimum or maximum exists for this scale.
2 secondary outcomes
Change of Patient-report NPS
Time frame: from baseline to post-intervention (4 weeks)
Change of Informant-rated NPS
Time frame: from baseline to post-intervention (4 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36623419Turnbull A, Anthony M, Tadin D, Porsteinsson AP, Heffner K, Lin FV. Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia. Cortex. 2023 Feb;159:131-141. doi: 10.1016/j.cortex.2022.10.015. Epub 2022 Dec 17.
- 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.
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 tDCS in people with Mild Cognitive Impairment and Neuropsychiatric Syndrome, run by University of Rochester 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 3 inclusion and 6 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 7 Nov 2023. 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?
Yes. Results are posted in the registry (first posted 7 Nov 2023). 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?
Change of C3 Activation (NPS-shared Neural Circuit Measure (time frame: from baseline to post-intervention (4 weeks)). The study lists 2 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 NCT04099524, 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 7 Nov 2023.