Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

• ClinicalTrials.gov Identifier: NCT02155946
• Recruitment Status: Completed
• First Posted: June 4, 2014
• Results First Posted: September 1, 2022
• Last Update Posted: September 1, 2022
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

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	Not Applicable

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 (Clinical Trial)
• 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: December 1, 2014
• Actual Primary Completion Date: February 28, 2021
• Actual Study Completion Date: March 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: active tDCS + mnemonic strategy training; Group receives active brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation
Active Comparator: sham tDCS + mnemonic strategy training; Group receives sham brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Sham (placebo)
Active Comparator: active tDCS + autobiographical memory recall; Group receives active brain stimulation plus reminiscence training	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation
Active Comparator: sham tDCS + autobiographical memory recall; 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 :

1. Face-name Memory Test Performance [ Time Frame: change from baseline to post session 5 (day 5 after baseline) ]
   Raw number of face-name pairs correctly recalled with a maximum of 15 points; higher values are better at each time point. Change at post-session 5 (day 5 after baseline)) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline).
2. Object Location Association Memory Test Performance - Cued Recall Condition [ Time Frame: change from baseline to post session 5 (day 5 after baseline) ]
   Performance measured using deviation from target position (in centimeters). Higher values indicate worse performance. Change at post-session 5 (day 5 after baseline) calculated relative to baseline performance (positive differences indicate decline; negative values indicate improvement).
3. fMRI Betaweight Change [ Time Frame: change from baseline to post session 5 (day 5 after baseline) ]
   Changes in task related blood oxygen dependent signal (BOLD) activation for the face-name (novel post > novel pre) contrast in the left inferior frontal gyrus (pars triangularis, pars orbitalis, pars opercularis). Data are preliminary betaweights for the above noted contrast. Positive values reflect increased BOLD signal while negative values represent reduced BOLD signal. Not all participants were able to complete fMRI, which explains sample size discrepancies with other outcome measures.

Secondary Outcome Measures :

1. Prose Memory [ Time Frame: change from baseline to post Session 5 (day 5 after baseline) ]
   Performance on the Ecological Memory Simulations- Medical Instructions subtest. Raw points where higher values reflect better performance at each time point (0-15 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline.
2. MMQ - Strategy Subscale [ Time Frame: change from baseline to post session 5 (day 5 after baseline) ]
   Changes on the Multifactorial Memory Questionnaire - strategy subscale. Raw points where higher values reflect better performance at each time point (0-76 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline.
3. Spatial Navigation [ Time Frame: change from baseline to post session 5 (day 5 after baseline) ]
   Performance on Ecological Memory Simulations routes subtest (serial order). Higher values indicate better performance at each time point (0-9 possible points at each time point). Change from baseline is reported (post-session day 5 vs. baseline) so higher values indicate better recall while negative values indicate decline.

Other Outcome Measures:

1. Planned (Tertiary) Analyses of Patient-specific Characteristics That Affect Treatment Outcome [ Time Frame: change from baseline post treatment (within ~ 96 hours of session 5) ]
   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.
2. Electric Field Effects [ Time Frame: Electrical field is estimated using baseline MRI T1 scan. ]
   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)
3. Brain Morphology [ Time Frame: Measured at baseline ]
   Magnetic Resonance Imaging based measure of brain volume (in percent of intracranial volume; higher values reflect larger brain size)

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 88 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Exclusion Criteria:

• History of neurological disease or injury
• History of severe mental illness
• Current untreated alcohol or substance abuse
• Other conditions may exclude; please discuss with contact

Contacts and Locations

Locations

United States, Michigan

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States, 48105

Sponsors and Collaborators

VA Office of Research and Development

Investigators

• Principal Investigator: Benjamin M. Hampstead, PhD; VA Ann Arbor Healthcare System, Ann Arbor, MI

  Study Documents (Full-Text)

Documents provided by VA Office of Research and Development:

Study Protocol  [PDF] July 1, 2022

Statistical Analysis Plan  [PDF] July 1, 2022

Informed Consent Form  [PDF] November 14, 2019

More Information

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT02155946
• Other Study ID Numbers: N1534-R
• First Posted: June 4, 2014
• Results First Posted: September 1, 2022
• Last Update Posted: September 1, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by VA Office of Research and Development:

Aging; Alzheimer's Disease/Dementia; Cognitive Disorders; Imaging; Magnetic Resonance Imaging (MRI); Neurology; Physical Medicine & Rehabilitation; transcranial direct current stimulation

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders