CogT BEEM Study (a tDCS Study) | NCT04099524

NCT04099524

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
R21MH120734	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
National Institute of Mental Health (NIMH)	NIH

Description Module

Brief 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). 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.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	Device: tDCS

Interventions

Name	Type	Description	Arm Group Labels	Other Names
tDCS	Device	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	from baseline to post-intervention (4 weeks)

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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)

Exclusion Criteria:

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.
1. Presence of any neurological or vascular disorders (e.g. - Multiple Sclerosis [MS], Traumatic Brain Injury [TBI], chronic heart failure [CHF], Parkinson's disease [PD]);
2. Clinical diagnosis of dementia as defined by the most recent version of the DSM;
3. Current enrollment in another study aimed at improving cognitive abilities and/or emotional well-being;
4. MRI contraindications (e.g. - pacemaker, implantable cardioverter defibrillator [ICD], aneurysm clips, severe claustrophobia);
5. 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).

Facility	Status	City	State	ZIP	Country	Contacts
Cabin, Ur		Rochester	New York	14642-0001	United States

PubMed Identifier	Type	Citation	Retractions
36623419	Derived	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.

Arm/Group Information

ID	Title	Description
FG000	Active tDCS	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. tDCS: 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.
FG001	Sham tDCS	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. tDCS: 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.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Active tDCS	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. tDCS: 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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

AR(1) covariance matrix with Generalized Estimating Equation (GEE) model. Data from 35 subjects (18 from intervention and 17 from control) were included in the data analysis on LSMC: in addition to the one participant that withdrew, one participant's data was excluded for excessive motion during MRI scanning, two for issues with co-registration and normalization, and one did not complete MRI scanning at timepoint 2 due to claustrophobia.

Posted

Mean

Standard Deviation

change of arbitrary unit LPG activation

from baseline to post-intervention (4 weeks)

ID	Title	Description
OG000	Active tDCS	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. tDCS: 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.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Active tDCS	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. tDCS: 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.

ID	Term
D003072	Cognition Disorders
D019965	Neurocognitive Disorders
D001523	Mental Disorders

ID	Term
D004599	Electric Stimulation Therapy
D013812	Therapeutics
D003295	Convulsive Therapy
D013000	Psychiatric Somatic Therapies