Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

Sponsor

VA Office of Research and Development (U.S. Fed)

Overall Status

Completed

CT.gov ID

NCT02155946

Collaborator

(none)

107

Enrollment

Location

Arms

Actual Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aging US population threatens to overwhelm our healthcare infrastructure, especially since the rate of Alzheimer's disease (AD) alone is expected to triple in the coming decades. Memory cause functional impairment, reduced quality of life, increased caregiver burnout, and eventual institutionalization. The diagnosis of mild cognitive impairment (MCI) identifies those with memory deficits but who remain relatively independent in everyday life. MCI provides a window for interventions that target memory functioning. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from different types of memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more "basic" science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment Alzheimer's Disease	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit	N/A

Detailed Description

Enrollment and interactions/interventions are temporarily paused due to COVID-19 and are expected to resume in the future. This is not a suspension of IRB approval.

The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more "basic" science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

The general purpose of this study is to examine the effects of two types of treatments for memory impairment in those with mild cognitive impairment (MCI). One form of treatment is cognitive rehabilitation, which involves teaching new ways to learn and remember information. The second form of treatment uses a type of electrical brain stimulation called transcranial direct current stimulation (tDCS) to increase activity in certain brain areas that may be involved with memory. We will use brain imaging to see whether these treatments changed how individuals learn and remember information. We will also use cognitive tests and questionnaires to examine whether memory (and related abilities) changed because of treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

107 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

Actual Study Start Date :

Dec 1, 2014

Actual Primary Completion Date :

Feb 28, 2021

Actual Study Completion Date :

Mar 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Group receives active brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Active brain stimulation
Sham Comparator: Arm 2 Group receives sham brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Sham (placebo)
Active Comparator: Arm 3 Group receives active brain stimulation plus reminiscence training	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Active brain stimulation
Active Comparator: Arm 4 Group receives sham brain stimulation plus reminiscence training	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit Sham (placebo)

Outcome Measures

Primary Outcome Measures

Face-name memory test performance [change from baseline to post, baseline to 3 month follow-up, and post to 3 month follow-up]
Performance measured using percent correct
Object Location Association memory test performance [change from baseline to post, baseline to 3 month follow-up, and post to 3 month follow-up]
Performance measured using deviation from target position
fMRI [change from baseline to post, baseline to 3 month follow-up, and post to 3 month follow-up]
Changes in task related and resting state BOLD activation/connectivity.

Secondary Outcome Measures

Objective memory test performance [change from baseline to post, baseline to 3 month follow-up, and post to 3 month follow-up]
Performance on prose (medical instructions) and spatial (navigation) memory tasks
Subjective memory test performance on the MMQ [change from baseline to post, baseline to 3 month follow-up, and post to 3 month follow-up]
Changes on the Multifactorial Memory Questionnaire

Other Outcome Measures

Planned (tertiary) analyses of patient-specific characteristics that affect treatment outcome [change from baseline post treatment (within ~ 96 hours) & 3 months]
Planned analyses to examine patient specific characteristics that affect treatment efficacy and would be vital for clinical translation at the individual patient level. Effect of level of cognitive functioning, measured via neuropsychological test performance at baseline, will be evaluated on magnitude of change at post-treatment and 3 month follow-up. Scores range from -3 to +3 standard deviations.
Electric field effects [change from baseline post treament (within ~96 hours)]
Finite element model based measurement of electric field in the targeted brain regions (Values range from 0 to no theoretical upper limit with higher values reflecting more electrical current; most values will be under 0.5 V/m)
Brain morphology [Measured at baseline]
Magnetic Resonance Imaging based measure of brain volume (in percent of intracranial volume; higher values reflect larger brain size)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 88 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

General inclusion criteria (all patients):

All medications stable for approximately 2-3 months;
No history of severe mental illness;
No current untreated alcohol or substance abuse/dependence;
English as native and preferred language;
MRI-compatible if taking part in fMRI studies
Able to give informed consent.

MCI Inclusion Criteria:

Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician