Analysis of Inflammatory Predictors and Gene Expression in Patients With Mild Cognitive Impairment
June 14, 2021 updated by: Suellen Marinho Andrade, Federal University of Paraíba
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
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.
Study Overview
Status
Unknown
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Anticipated)
40
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
65 years to 85 years (Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: active tDCS
tDCS active, for 30 minutes for 5 consecutive days, with an anode positioned in the left dorsolateral prefrontal cortex and cathode electrode placed over the right supraorbital area.
The EEG International 10-20 system will be taken as a reference.
The current intensity will be defined from computational modeling, using Nuclear Magnetic Resonance (MRI) to estimate and individualize a dose to be administered.
|
Active intervention
|
|
Sham Comparator: Sham tDCS
The electrodes will be positioned in the same way as in the intervention group.
However, individuals in this group will receive a stimulation that will last only 20-30 seconds.
Subsequently, the device is switched off, no longer emitting current.
|
Direct Current Transcranial Stimulation - Sham intervention
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Cognitive Function
Time Frame: Evaluations will be carried out in the pre-intervention (T0)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Inflammatory biomarkers
Time Frame: The assessment will be carried out at time T1 (baseline).
|
We will analyze three inflammatory cytokines Il-6, Il-10 and tumor necrosis factor (TNFα) 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).
|
|
Genetic Biomarkers
Time Frame: The assessment will be carried out at time T1 (baseline)
|
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)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
June 1, 2021
Primary Completion (Anticipated)
August 1, 2021
Study Completion (Anticipated)
April 1, 2022
Study Registration Dates
First Submitted
February 9, 2021
First Submitted That Met QC Criteria
June 14, 2021
First Posted (Actual)
June 22, 2021
Study Record Updates
Last Update Posted (Actual)
June 22, 2021
Last Update Submitted That Met QC Criteria
June 14, 2021
Last Verified
February 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CCL/Genes
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
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