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

Mild Cognitive Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04943003
• Other study ID #: tDCS in MCI
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 26, 2021
• Est. completion date: December 25, 2024

Study information

• Verified date: July 2021
• Source: Federal University of Paraíba
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 25, 2024
• Est. primary completion date: December 25, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Dementia
• Genetic Predisposition to Disease
• Mild Cognitive Impairment

Intervention

Device:
• Transcranial Direct Current Stimulation (tDCS)
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.

Locations

Country	Name	City	State
Brazil	Federal University of Paraíba,Department of Psychology	João Pessoa	Paraíba

Sponsors (1)

Lead Sponsor	Collaborator
Suellen Marinho Andrade

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Digit Span Memory Test	This is one of the main tasks used in short-term memory assessment, where the examiner asks the patient to repeat a series of numbers (eg 2-5, 3-6-7). The first sequence starts with two digits, and after each correct answer the examiner adds one digit to the next sequence. The test is composed of two parts, in forward and reverse order, allowing the assessment of short-term memory storage capacity and its executive component.	The evoluations will be carried out in Pre-intervention (T0)
Secondary	Digit Span Memory Test	This is one of the main tasks used in short-term memory assessment, where the examiner asks the patient to repeat a series of numbers (eg 2-5, 3-6-7). The first sequence starts with two digits, and after each correct answer the examiner adds one digit to the next sequence. The test is composed of two parts, in forward and reverse order, allowing the assessment of short-term memory storage capacity and its executive component.	The evoluations will be performed up to one week after the stimulation protocol (T1)
Secondary	Beck Depression Scale II and Beck Anxiety Inventory	The Beck II Depression Scale, a self-report instrument for depression, has 21 items that reveal how the individual has felt during the last two weeks (including the current day), in which there are four answers for each one (with a score ranging from 0 to 3). The total score is the sum of individual items, whose maximum score can reach 63 points, being classified into levels: mild, moderate and severe.; The Beck Anxiety Inventory consists of 21 items that assess how the individual has been feeling during the last two weeks, including the current day, enabling the collection of information about anxiety symptoms. Each item has 4 options, among which one can be chosen by the participant (ranging from 0 to 3 the score of each option). The total score is calculated by adding the individual response for each item, with a maximum score of 63 points. The results will be used as a prediction of response to neurostimulation.	The evoluations will be carried out in Pre-intervention (T0)
Secondary	Beck Depression Scale II and Beck Anxiety Inventory	The Beck II Depression Scale, a self-report instrument for depression, has 21 items that reveal how the individual has felt during the last two weeks (including the current day), in which there are four answers for each one (with a score ranging from 0 to 3). The total score is the sum of individual items, whose maximum score can reach 63 points, being classified into levels: mild, moderate and severe.; The Beck Anxiety Inventory consists of 21 items that assess how the individual has been feeling during the last two weeks, including the current day, enabling the collection of information about anxiety symptoms. Each item has 4 options, among which one can be chosen by the participant (ranging from 0 to 3 the score of each option). The total score is calculated by adding the individual response for each item, with a maximum score of 63 points. The results will be used as a prediction of response to neurostimulation.	The evoluations will be performed up to one week after the stimulation protocol (T1)
Secondary	Genetic susceptibility (ApoE)	For ApoE allele genotyping, the researchers will follow the recommendations proposed by Crook, Hardy & Duff (1994) and Wenham, Newton, & Price (1991), and the genomic DNA will be amplified by a Polymerase Chain Reaction (PCR). The results will be used as a prediction of response to neurostimulation.	The evoluations will be carried out in Pre-intervention (T0)
Secondary	Electroencephalography	Brain electrical activity will be captured using the BrainVision actiCHamp32 equipment (Brain vision, Herrsching, Germany), using 32 Ag/AgCl electrodes, which will be positioned and fixed based on the 10-20 International System. The data will be used to assess brain electrical activity at baseline.	The evoluations will be carried out in Pre-intervention (T0)
Secondary	Electroencephalography (EEG)	Brain electrical activity will be captured using the BrainVision actiCHamp32 equipment (Brain vision, Herrsching, Germany), using 32 Ag/AgCl electrodes, which will be positioned and fixed based on the 10-20 International System. The regions of interest to be monitored are: prefrontal, frontal, parietal, temporal and occipital region, bilaterally (Fz, F3, F7, FT9, FC5, FC1, C3, T7, TP9, CP5, CP1, Pz, P3, P7, O1, Oz, O2, P4, P8, TP10, CP6, CP2, Cz, C4, T8, FT10, FC6, FC2, F4, F8, Fp2, Fp1), in the silent condition in the eyes and eyes closed states , for five minutes each, totaling 10 minutes of collection for each subject. The results will be used as a prediction of response to neurostimulation.	The evoluations will be performed up to one week after the stimulation protocol (T1)
Secondary	Magnetic Resonance Imaging-MRI	High-resolution anatomical images will be acquired using a T1-weighted fast gradient sequence prepared by three-dimensional magnetization with the following parameters: repetition time (TR) = 1900ms, echo time (TE) = 2.2 ms, inversion time (TI) = 900 ms, inversion angle (FA) = 9°, number of slices = 176, slice thickness = 1 mm, voxel size = 1 × 1 × 1 mm 3 and matrix = 256 × 256. The results will be used for computational modeling and to assess brain electrical activity at baseline.	The evoluations will be carried out in Pre-intervention (T0)
Secondary	Magnetic Resonance Imaging-MRI	High-resolution anatomical images will be acquired using a T1-weighted fast gradient sequence prepared by three-dimensional magnetization with the following parameters: repetition time (TR) = 1900ms, echo time (TE) = 2.2 ms, inversion time (TI) = 900 ms, inversion angle (FA) = 9°, number of slices = 176, slice thickness = 1 mm, voxel size = 1 × 1 × 1 mm 3 and matrix = 256 × 256. The results will be used as a prediction of response to neurostimulation.	The evoluations will be performed up to one week after the stimulation protocol (T1)