Study of Neurobiological Predictors of Response to Non-invasive Neurostimulation and Genetic Susceptibility to Dementia in Patients With Amnestic Mild Cognitive Impairment

NCT04943003 | Unknown

• 1 other identifier: tDCS in MCI
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Transcranial Direct Current Stimulation is a non-invasive neuromodulatory technique that results in the clinical improvement of patients with Mild Cognitive Impairment, a prodromal condition for the onset of dementia. The responses to treatment depend on the characteristics of the patients and the parameters adjusted in the equipment, which makes the modeling of electric fields imperative to maximize the safety profile and therapeutic potential of the technique. The study of neurobiological predictors of response to non-invasive neurostimulation and genetic susceptibility can elucidate current effects according to the individual's profile. The objectives of this study are to observe the effects of Transcranial Direct Current Stimulation with optimized/customized parameters in patients with amnestic CCL, considering the subjects' genetic susceptibility to Alzheimer's Disease and neurobiological markers. This is a randomized, triple-blind, sham-controlled clinical trial. Neuropsychological tests and a sociodemographic and clinical questionnaire will be used to assess and characterize the subjects. Participants captured by the Laboratory of Studies in Aging and Neuroscience at the Federal University of Paraíba will be divided into 02 groups, each with 25 patients, totaling 50 volunteers: Active - participants who will receive real current; Sham - participants who will receive simulated stimulation. Participants entered through the eligibility criteria will be randomly allocated in a simple way, at a rate of 1:1. Payment parameters will be customized by Computational Modeling with the aid of the SimNIBS Program and Nuclear Magnetic Resonance. The electroencephalogram and evaluation of polymorphisms of the gene encoding Apolipoprotein E examined as predictors of response. Data will be processed from the Statistical Package for Social Sciences® (20.0) Software, applying the Student test for continuous variables or chi-square for categorical variables. Predictive analysis will be conducted from Machine Learning. It is expected to find improvements in the scores of memory and general cognition tests after the intervention protocol with tDCS with individualized dose in the group that will receive an intervention, compared to the simulated neurostimulation group. These obtained results optimize the practice, elucidating issues still present due to the different applications of the technique produced in the literature on the subject.

Conditions

Mild Cognitive Impairment

Keywords

Mild Cognitive Impairment; tDCS; Computational modeling

Outcome Measures

Primary Outcomes (2)

• Mini Mental State Examination (MMSE) (T0)

  To assess the primary outcome, the Mini Mental State Examination (MMSE) o will be used, developed in the United States and published in 1975, whose maximum score is 30 points and includes questions about memory, attention , orientation, language, and visuospatial skills. We will adopt the 24-point score for the standard cut, following recommendations expressed in the literature. In order to avoid false positives and false negatives, we will perform the stratification by levels or years of schooling, as educational level is the main predictor of MMSE performance. Authors recorded good internal consistency (0.62 to 0.79) and a high test-retest reliability of the MMSE, ranging from 0.76 to 0.90, being a reliable instrument to detect CCL and AD .

  The evoluations will be carried out in Pre-intervention (T0)

• Mini Mental State Examination (MMSE) (T1)

  To assess the primary outcome, the Mini Mental State Examination (MMSE) o will be used, developed in the United States and published in 1975, whose maximum score is 30 points and includes questions about memory, attention , orientation, language, and visuospatial skills. We will adopt the 24-point score for the standard cut, following recommendations expressed in the literature. In order to avoid false positives and false negatives, we will perform the stratification by levels or years of schooling, as educational level is the main predictor of MMSE performance. Authors recorded good internal consistency (0.62 to 0.79) and a high test-retest reliability of the MMSE, ranging from 0.76 to 0.90, being a reliable instrument to detect CCL and AD .

  The evoluations will be performed up to one week after the stimulation protocol (T1)

Secondary Outcomes (9)

• Digit Span Memory Test

  The evoluations will be carried out in Pre-intervention (T0)

• Digit Span Memory Test

  The evoluations will be performed up to one week after the stimulation protocol (T1)

• Beck Depression Scale II and Beck Anxiety Inventory

  The evoluations will be carried out in Pre-intervention (T0)

• Beck Depression Scale II and Beck Anxiety Inventory

  The evoluations will be performed up to one week after the stimulation protocol (T1)

• Genetic susceptibility (ApoE)

  The evoluations will be carried out in Pre-intervention (T0)

Study Arms (2)

Active tDCS

EXPERIMENTAL

SimNIBS will be used for modeling. It is a free and open source software package for the simulation of electric field induced by tDCS in the individual brain. Modeling will be done using T1-weighted anatomical images of each subject to reconstruct a high-resolution head model of each individual. For electrode placement, we will simulate areas F5 and F6, according to the EEG 10-20 system, for the anode and cathode, respectively, targeting the left and right Dorsolateral Prefrontal Cortex (DLPFC). This group will receive active tDCS, for 30 minutes and for 5 consecutive days, in two weeks, with an anode positioned on the left DLPFC and a cathode electrode placed on the right supraorbital area.

Device: Transcranial Direct Current Stimulation (tDCS)

Sham tDCS

SHAM COMPARATOR

The electrodes will be placed in the same way as in the Active tDCS group. However, individuals in this group will receive a stimulation that will last only 20-30 seconds. Afterwards, the device will be turned off, no longer emitting current.

Device: Transcranial Direct Current Stimulation (tDCS)

Interventions

Transcranial Direct Current Stimulation (tDCS) DEVICE

Initially, a measuring tape will be used to make the markings and measurements necessary for placing the electrodes. Regarding neurostimulation, the tDCS device is simple and portable, consisting of four main components: two electrodes (anode and cathode), an ammeter (electric current intensity meter), a potentiometer (voltage controller between electrodes) and a set of batteries. We will use the TCT-Research Neurostimulator, developed by Trans Cranial Technologies (Hong Kong, China), Regarding the protocols, the Active tDCS group will receive active tDCS for 30 minutes and for 5 consecutive days, in two weeks, with an anode positioned on the left DLPFC and a cathode electrode placed on the right supraorbital area. The 10-20 International EEG system will be taken as a reference. The current intensity will be defined from computational modeling, using Nuclear Magnetic Resonance (NMR) to estimate and individualize the dose to be administered.

Active tDCS; Sham tDCS

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Individuals diagnosed with Mild Cognitive Impairment (MCI);
• Both sexes;
• Aged 65 years or older, without a diagnosis of dementia will be included.

You may not qualify if:

• Unstable medical conditions;
• Patients with metallic implants and pacemakers;
• Epileptics;
• Using drugs/alcohol, regular use of hypnotics and benzodiazepines up to two weeks before the start of the study;
• People who have been using medication with cholinergic inhibitors for more than two months before this clinical trial

Sponsors & Collaborators

• Suellen Marinho Andrade: lead

Study Sites (1)

Federal University of Paraíba,Department of Psychology

João Pessoa, Paraíba, 58051-900, Brazil

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: All examiners will be blinded to the type of treatment the patient received (active stimulation or sham) and other assessments. Thus, all guidelines established by CONSORT 2010 (Consolidated Standards of Reporting Trials) will be complied with, as pointed out by Moher et al. (2010), with variable control following systematized and countersigned procedures: random sequence generation, allocation concealment, blinding of participants and professionals, blinding of outcome evaluators and attrition bias (loss analysis using the last observation carried forward method) (Higgins \& Green, 2011).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants will be divided into 02 groups, each with 25 patients, totaling 50 volunteers: Active - participants who will receive real current; Sham - participants who will receive simulated stimulation. Participants entered into the study through the eligibility criteria will be randomly allocated in a simple way, at a rate of 1:1.

Study Record Dates

• First Submitted: June 6, 2021
• First Posted: June 29, 2021
• Study Start: August 26, 2021
• Primary Completion: December 25, 2022
• Study Completion: December 25, 2024
• Last Updated: July 27, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)