Analysis of Inflammatory Predictors and Gene Expression in Patients With Mild Cognitive Impairment

Cognitive Decline Clinical Trial

Official title:

Analysis of Inflammatory Predictors and Differences in Gene Expression in Patients With Cognitive Impairment Responders and Non-responders to Neurostimulation: Clinical Trial, Double-Blind, Randomized

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04934423
• Other study ID #: CCL/Genes
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2021
• Est. completion date: April 2022

Study information

• Verified date: February 2021
• Source: Federal University of Paraíba
• Contact: Suellen Andrade
• Phone: 83 99937-1471
• Email: suellenandrade[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A randomized, double-blind, placebo-controlled clinical trial will be conducted, using data from participants who met the diagnostic criteria for mild cognitive impairment and who participated in a primary clinical trial that investigated the effectiveness of treatment with tDCS for patients with this pathology. The study in question seeks to investigate differences in inflammatory profile and gene expression in peripheral blood of patients with MCI responders and non-responders to treatment with tDCS, where it is intended to establish a profile of biomarkers that can predict disease progression. Primary study participants will be assessed previously for eligibility, then randomized to receive sham or active tDCS. Then, they will be invited to participate in the prediction analysis study to identify the inflammatory profile and gene expression. The participants' venous blood will be collected during the clinical examination on the first day of treatment, before the first session of tDCS, with a new collection after the last session, that is, at the baseline and the end point of our study.

Description:

Healthy aging is associated with several changes in cortical function and these physiological differences are often interpreted as successful adaptation when cognitive performance is maintained; however, cognitive ability is not always preserved in aging. Mild cognitive impairment (MCI) is a cognitive decline syndrome commonly referred to as an intermediate phase between the expected cognitive decline of aging and pathological cognitive decline linked to dementia and generally does not interfere with daily activities. Pharmacological interventions have shown little positive impact and fail to demonstrate realizable benefits in mitigating cognitive decline in individuals with MCI and in preventing progression to Alzheimer's disease (AD). With this, there is a growing interest in exploring the benefits of non-pharmacological interventions such as Transcranial Direct Current Stimulation (tDCS), which can be a treatment modality to address the electrophysiological onset, deficits of metabolic and functional neural activation observed in MCI. Although tDCS has been studied in different dementias, there are still few studies investigating its use for MCI, with a significant lack of research in this area. Another issue to be explored is changes in the levels of biomarkers in body fluids and in specific brain regions of these patients, as they may allow the detection of cognitive changes even before the appearance of MCI. Different proteomic and genetic markers can result in a more accurate prediction of who will develop AD dementia in the future. The study in question seeks to investigate differences in the inflammatory profile and gene expression in the peripheral blood of patients with MCI responders and non-responders to treatment with tDCS, where it is intended to establish a profile of biomarkers that can predict the progression of the disease. Data from participants who met the diagnostic criteria for MCI and who participated in a clinical trial that investigated the effectiveness of treatment with tDCS for patients with this pathology will be used. Thus, it is necessary to mention the importance of early identification of the incipient forms of cognitive deficits, for the development of effective treatments. Several randomized controlled trials are underway to try to provide clinical evidence for the development of biomarkers that should provide the clinician with new tools to identify and treat MCI.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: April 2022
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

• Individuals diagnosed with CCL will be included

• Individuals of both sexes, aged 65 and over

• Individuals who do not have diagnosis of dementia

Exclusion Criteria:

• Subjects with unstable medical conditions

• Patients with metallic implants and pacemakers

• Epileptic patients

• Individuals using drugs / alcohol

• Those who are under regular use of hypnotics and benzodiazepines up to two weeks before the start of the study

• Those who are using medication with cholinergic inhibitors for more than two months before this clinical trial

Related Conditions & MeSH terms

• Cognitive Decline
• Cognitive Dysfunction

Intervention

Device:
• Direct Current Transcranial Stimulation - tDCS
Active intervention
• Sham Intervention
Direct Current Transcranial Stimulation - Sham intervention

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Federal University of Paraíba

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cognitive Function	To assess the primary outcome, the Mini Mental State Examination (MMSE) or Mini-Mental State Examination (MMSE), developed in the United States and published in 1975, will be used, whose maximum score is 30 points and includes questions about memory, attention , orientation, language and visuospatial skills (Folstein, Folstein, & McHugh, 1975).; We will adopt the 24-point score for the standard cut, following recommendations expressed in the literature (Anthony, Le Resche, Niaz, Von Korff, & Folstein, 1982; Folstein, Folstein, & McHugh, 1975). 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 (Bertolucci, Brucki, Campacci, & Juliano, 1994).	Evaluations will be carried out in the pre-intervention (T0)
Secondary	Inflammatory biomarkers	We will analyze three inflammatory cytokines Il-6, Il-10 and tumor necrosis factor (TNFa) from a blood sample to compare their levels between the group treated with active current, responders and non-responders to neurostimulation.	The assessment will be carried out at time T1 (baseline).
Secondary	Genetic Biomarkers	For the genotyping of Neuregulin and alpha-synuclein markers, researchers will follow the method developed by Chomczynski and Sacchi (1987). Total RNA from peripheral blood sample will be extracted using Trizol reagent (Invitrogen). The results will be used as a prediction of the response to neurostimulation.	The assessment will be carried out at time T1 (baseline)