Cognitive DeclineNCT04934423
Analysis of Inflammatory Predictors and Gene Expression in Patients With Mild Cognitive Impairment
A study testing Direct Current Transcranial Stimulation - tDCS in people with Cognitive Decline, run by Federal University of Paraíba.
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. Read more about this study
- Who is it for?
- Ages 65 to 85 years
- Conditions the study is for
- Cognitive Decline
- What is being tested?
- Direct Current Transcranial Stimulation - tDCS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Jun 2021to Apr 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 85 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Individuals diagnosed with CCL will be included
- Individuals of both sexes, aged 65 and over
- Individuals who do not have diagnosis of dementia
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
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
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.
Read the 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.
- Conditions
- Cognitive Decline
- Being tested
- Direct Current Transcranial Stimulation - tDCS, Sham Intervention
- Keywords
- Mild cognitive impairment, Direct Current Transcranial Stimulation, Inflammatory biomarkers, Gene expression
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Direct Current Transcranial Stimulation - tDCSDevice
Active intervention
Sham InterventionDevice
Direct Current Transcranial Stimulation - Sham intervention
| Study group | Role | What they receive |
|---|---|---|
| active tDCS | Experimental | 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. Receives: Device: Direct Current Transcranial Stimulation - tDCS |
| Sham tDCS | Sham comparator | 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. Receives: Device: Sham Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Evaluations will be carried out in the pre-intervention (T0)
Secondary outcomes (2)
Inflammatory biomarkers
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.
Measured: The assessment will be carried out at time T1 (baseline).
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.
Measured: The assessment will be carried out at time T1 (baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2021
- Study startJun 2021 (estimated)
- Primary completionAug 2021 (estimated)
- Study completionApr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DeclineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, double-blind, placebo-controlled clinical trial will be conducted with patients diagnosed with Mild Cognitive Impairment, submitted to Direct Current Transcranial Stimulation sessions in a primary clinical trial. Both studies are in accordance with the guidelines of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) (Moher \& Chan, 2014), which is considered a tool composed of minimal contents of a clinical trial protocol.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal University of Paraíba
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suellen Marinho Andrade, Federal University of Paraíba
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04934423
- Sponsor's protocol ID
- CCL/Genes
- Status last verified
- Feb 2021
- First submitted
- 9 Feb 2021
- Last updated
- 22 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04934423
- Acronym / sponsor ID
- CCL/Genes
- Conditions
- Cognitive Decline
- Keywords
- Mild cognitive impairment, Direct Current Transcranial Stimulation, Inflammatory biomarkers, Gene expression
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Federal University of ParaíbaUniversity, hospital or other
- Study start
- Jun 2021 (estimated)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Apr 2022 (estimated)
- First posted
- 22 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, double-blind, placebo-controlled clinical trial will be conducted with patients diagnosed with Mild Cognitive Impairment, submitted to Direct Current Transcranial Stimulation sessions in a primary clinical trial. Both studies are in accordance with the guidelines of the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) (Moher \& Chan, 2014), which is considered a tool composed of minimal contents of a clinical trial protocol.
| Arm | Type | Receives |
|---|---|---|
| active tDCS | Experimental | Device: Direct Current Transcranial Stimulation - tDCStDCS 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. |
| Sham tDCS | Sham comparator | Device: Sham InterventionThe 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. |
Who may qualify
- Ages
- 65 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Individuals diagnosed with CCL will be included
- Individuals of both sexes, aged 65 and over
- Individuals who do not have diagnosis of dementia
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Direct Current Transcranial Stimulation - tDCSActive intervention | Device | active tDCS |
| Sham InterventionDirect Current Transcranial Stimulation - Sham intervention | Device | Sham tDCS |
Primary outcome
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).
2 secondary outcomes
Inflammatory biomarkers
Time frame: The assessment will be carried out at time T1 (baseline).
Genetic Biomarkers
Time frame: The assessment will be carried out at time T1 (baseline)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing Direct Current Transcranial Stimulation - tDCS in people with Cognitive Decline, run by Federal University of Paraíba.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Suellen Andrade (83 99937-1471, suellenandrade@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function (time frame: Evaluations will be carried out in the pre-intervention (T0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2021.