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CogT BEEM Study (a tDCS Study)

Primary Purpose

Mild Cognitive Impairment, Neuropsychiatric Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
tDCS
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Mild Cognitive Impairment

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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):

  1. In the past month, presence of > 2 symptoms; and
  2. 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).

Sites / Locations

  • Cabin, Ur

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

active tDCS

sham tDCS

Arm Description

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 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.

Outcomes

Primary Outcome Measures

Change of NPS-shared neural circuit
Change of activation in LPG in response to visual attention task (measured using task related fMRI) and resting FC strength between LPG and other regions within the NPS-shared neural circuit (resting fMRI)

Secondary Outcome Measures

Change of informant-rated NPS
Change of informant-rated NPI, the full version of 12 domains, including both frequency and severity (based on present symptom) scores in the past month. Of note, NPI-Q used in our preliminary study is a brief version of NPI.

Full Information

First Posted
September 19, 2019
Last Updated
June 8, 2022
Sponsor
University of Rochester
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1. Study Identification

Unique Protocol Identification Number
NCT04099524
Brief Title
CogT BEEM Study (a tDCS Study)
Official Title
Effectiveness of a Non-Invasive, Low-Intensity Brain Stimulation Approach in Addressing Emotional Regulation
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
December 6, 2019 (Actual)
Primary Completion Date
January 19, 2022 (Actual)
Study Completion Date
January 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Neuropsychiatric Syndrome

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
active tDCS
Arm Type
Experimental
Arm Description
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.
Arm Title
sham tDCS
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Device
Intervention Name(s)
tDCS
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change of NPS-shared neural circuit
Description
Change of activation in LPG in response to visual attention task (measured using task related fMRI) and resting FC strength between LPG and other regions within the NPS-shared neural circuit (resting fMRI)
Time Frame
from baseline to 8-week after delivering 14-session intervention
Secondary Outcome Measure Information:
Title
Change of informant-rated NPS
Description
Change of informant-rated NPI, the full version of 12 domains, including both frequency and severity (based on present symptom) scores in the past month. Of note, NPI-Q used in our preliminary study is a brief version of NPI.
Time Frame
from baseline to 8-week after delivering 14-session intervention

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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. 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).
Facility Information:
Facility Name
Cabin, Ur
City
Rochester
State/Province
New York
ZIP/Postal Code
14642-0001
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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CogT BEEM Study (a tDCS Study)

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