Ignite Creation Date:
2024-07-17 @ 10:47 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06467253
Status:
RECRUITING
Last Update Posted:
2024-06-20
First Post:
2024-03-21
Brief Title:
Comparison of Two Non-invasive Neuromodulation Techniques as Synergistic Therapy to Cognitive Stimulation in Amnestic Mild Cognitive Impairment aMCI
Sponsor:
Instituto Nacional de Psiquiatría Dr Ramón de la Fuente
Organization:
Instituto Nacional de Psiquiatría Dr Ramón de la Fuente
Study Overview
Official Title:
Comparison of Two Non-invasive Neuromodulation Techniques as Synergistic Therapy to Cognitive Stimulation in Amnestic Mild Cognitive Impairment aMCI Genetic Characterization Proteins Associated With Neurogenesis Clinical Neuroimaging and Electrophysiological Markers
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a comparative double-blind randomized controlled clinical trial for people with Amnestic Mild Cognitive Impairment The investigators will compare the effects of two non-invasive neuromodulation techniques Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation combined with cognitive stimulation These non-invasive neuromodulating techniques will be applied as a treatment alternative to be able to compare non-invasive techniques with cognitive stimulation CS alone taking into account clinical and neuropsychological evaluations in addition to 1 the known clinical risk factors physical activity comorbidities treatment etc that allow the investigators to characterize the participants 2 characterize the participants with genetic biomarkers using the APOE4 CR1 COMT TREM2 and ABCA7 genotype 3 document the biological effects related to neurogenesis from olfactory epithelial neural progenitor cells and solubles factors of serum 4 use hippocampal volume cortical thickness of the medial temporal cortex and parietal cortex by means of structural magnetic resonance imaging and the default mode network by means of functional magnetic resonance imaging at rest as a biomarker of response to treatment and 5 associate the response to treatment with changes in Motor Evoked Potential MEP amplitude and latency in order to generate a response-to-treatment biomarker with neuromodulators in Mild Cognitive Impairment MCI and changes in electroencephalogram
Detailed Description:
Mild Cognitive Impairment can be described as an intermediate stage between intact cognition and dementia this study has become a global priority due to alarming changes in the population pyramid that place the world population at a higher risk of developing dementia The global prevalence of MCI is between 15-20 in people over 60 years old In 2012 a prevalence of MCI of 32 was found in Mexico City which encourages the researchers to study this phenomenon to achieve early detection and create interventions that could delay the onset of dementia and even prevent it Symptomatology is distinguished by deficits in one or more cognitive domains through formal tests applied repeatedly the individual can manifest symptoms directly by identifying as different from a previous state andor being corroborated by an informant The amnestic cognitive impairment aMCI occurs when the cognitive failure is limited only to the domain of episodic memory Generally there is a slight functional impairment for complex tasks but the basic and instrumental activities of daily life must be preserved Behavioral and psychological symptoms BPSD can occur Apathy anxiety and depression present in patients with mild cognitive impairment may represent an increased risk of dementia and in many cases can be the first symptoms to appear The evaluation is essential because BPSD are often controllable with treatment and appears in up to 77 of patients with MCI
Despite the need to stop the progression to dementia a MCI treatment is currently nonspecific focused on associated events with pharmacological and non-pharmacological measures aimed to reduce cognitive and neuropsychiatric symptoms Therapeutic methods that promote neuroplasticity for instance cognitive stimulation CS and non-invasive neuromodulatory techniques such as Repetitive Transcranial Magnetic Stimulation rTMS and Transcranial Direct Current Stimulation tDCS optimize performance by stimulating the neural network distributed around a dysfunctional circuit interacting with brain plasticity and inducing or increasing compensatory mechanisms This phenomenon could add to the cognitive reserve and interfere with the temporal evolution of the symptoms Thereby the rTMS and tDCS have been suggested as a possible treatment in aMCI These non-invasive alternatives rTMS and tDCS have shown efficacy as a treatment in other disorders but evidence is required on the efficacy tolerability and viability of the application in patients with amnesic MCI as well as the time that the effect of its application remains which creates the need of further studies with maintenance phases
In this project the researchers propose a clinical trial for participants with risk of developing dementia using rTMS and tDCS added to CS in an effectiveness comparison using strict placebo control methods which will only be used with rTMS and tDCS not with CS The non-invasive neuromodulating techniques will be applied as a treatment alternative to be able to compare the techniques with CS alone taking into account clinical and neuropsychological evaluations in addition to 1 the known clinical risk factors physical activity comorbidities treatment etc that allow to characterize patients 2 characterize the participants with genetic biomarkers using the APOE4 CR1 COMT TREM2 and ABCA7 genotype 3 document the biological effects related to neurogenesis from olfactory epithelial neural progenitor cells isolated before and after treatment In addition to the documentation of soluble factors secreted by olfactory epithelial neural progenitor cells what is relevant to the knowledge of the influence of peripheral serum on microglia This is crucial role in inflammation The evaluations will be performed at different time points such as Baseline T0 after first phase of treatment T115 sessionsweek of tDCSCS after maintenance T212 sessionsweek of tDCSCS and follow-up phase T31 year after treatment 4 use hippocampal volume cortical thickness of the medial temporal cortex and parietal cortex using structural magnetic resonance imaging and the default mode network using functional magnetic resonance imaging at rest as a biomarker of response to treatment and 5 associate the response to treatment with changes in Motor Evoked Potential MEP amplitude to generate a response-to-treatment biomarker with neuromodulators in MCI and changes in electroencephalogram EEG
Among the current limitations on knowledge of this disease many studies use biomarkers to predict MCI or progression to dementia and although most biomarkers are reported to be valuable in this setting few are compared with each other so this is currently difficult to understand the relative importance of the different biomarkers when used together For this reason the present project could be a contribution in the short and long term to detect changes that may or may not be related to each other and generate multiple lines of research
Population aging will continue to increase and therefore there will be a greater number of people with aMCI Currently there is no treatment that prevents the progression of aMCI to AD so the trend is to make earlier interventions aMCI is a condition of opportunity because the cognitive reserve of the patients has not been exhausted so developing studies with innovative treatments and few side effects that can change the evolution over time is important To that end understanding the etiology of this progression and designig treatments that delay or definitively stop aMCI are of importance to preserve the functionality of individuals with this condition
Clinical trials with rTMS and tDCS carried out in aMCI have already shown favorable results regarding episodic memory semantic memory and speed of information processing This trial will be able to contribute to the already reported findings that allow to identify better therapeutic approaches that support the standardization of the application of neuromodulatory techniques Besides the possible additive effect of neuromodulatory techniques and CS is well known but no studies are comparing between diferent interventions with each other The genetic characterization will be obtained an experimental biomarker of secretion proteins from olfactory epithelial neural progenitor cells together with the analysis of the neurogenic process occurring in the olfactory epithelium will be generated an experimental biomarker of serum and the effects soluble factors contained in serum on microglia will be generated neuroimaging and produce neurophysiological measures considered as possible neuroplasticity biomarkers MEPs and EEG associated with the response to non-pharmacological treatment will be recorded and evaluated if the parameters are related to clinical and cognitive characteristics With this therapeutic approach where non-invasive neuromodulatory techniques are combined with CS the aim is to improve the quality of care for patients with aMCI considering that neuromodulation alternatives can delay the process of deterioration in each patient admitted
The hypotheses in this study are 1 The combined application of non-invasive neuromodulation techniques with cognitive stimulation will significantly improve the cognitive performance of patients with aMCI compared to the single application of non-invasive neuromodulation techniques or cognitive stimulation alone 2 There will be differences in the protein expression in the olfactory epithelial neural progenitor cells of patients with aMCI who are treated with some non-invasive neuromodulation techniques and those who only receive cognitive stimulation 3 The soluble factors in the serum of patients with aMCI before and after treatment will differentially modulate microglia 4 There will be differences in brain morphology such as cortical thickness and surface area white matter integrity as well as structural connectivity between different brain areas before and after treatment with non-invasive stimulation techniques 5 There will be differences in the amplitude and latency of the MEP as well as changes in EEG of patients with aMCI who are treated with one of the non-invasive neuromodulation techniques and patients who only receive CS
Despite the need to stop the progression to dementia a MCI treatment is currently nonspecific focused on associated events with pharmacological and non-pharmacological measures aimed to reduce cognitive and neuropsychiatric symptoms Therapeutic methods that promote neuroplasticity for instance cognitive stimulation CS and non-invasive neuromodulatory techniques such as Repetitive Transcranial Magnetic Stimulation rTMS and Transcranial Direct Current Stimulation tDCS optimize performance by stimulating the neural network distributed around a dysfunctional circuit interacting with brain plasticity and inducing or increasing compensatory mechanisms This phenomenon could add to the cognitive reserve and interfere with the temporal evolution of the symptoms Thereby the rTMS and tDCS have been suggested as a possible treatment in aMCI These non-invasive alternatives rTMS and tDCS have shown efficacy as a treatment in other disorders but evidence is required on the efficacy tolerability and viability of the application in patients with amnesic MCI as well as the time that the effect of its application remains which creates the need of further studies with maintenance phases
In this project the researchers propose a clinical trial for participants with risk of developing dementia using rTMS and tDCS added to CS in an effectiveness comparison using strict placebo control methods which will only be used with rTMS and tDCS not with CS The non-invasive neuromodulating techniques will be applied as a treatment alternative to be able to compare the techniques with CS alone taking into account clinical and neuropsychological evaluations in addition to 1 the known clinical risk factors physical activity comorbidities treatment etc that allow to characterize patients 2 characterize the participants with genetic biomarkers using the APOE4 CR1 COMT TREM2 and ABCA7 genotype 3 document the biological effects related to neurogenesis from olfactory epithelial neural progenitor cells isolated before and after treatment In addition to the documentation of soluble factors secreted by olfactory epithelial neural progenitor cells what is relevant to the knowledge of the influence of peripheral serum on microglia This is crucial role in inflammation The evaluations will be performed at different time points such as Baseline T0 after first phase of treatment T115 sessionsweek of tDCSCS after maintenance T212 sessionsweek of tDCSCS and follow-up phase T31 year after treatment 4 use hippocampal volume cortical thickness of the medial temporal cortex and parietal cortex using structural magnetic resonance imaging and the default mode network using functional magnetic resonance imaging at rest as a biomarker of response to treatment and 5 associate the response to treatment with changes in Motor Evoked Potential MEP amplitude to generate a response-to-treatment biomarker with neuromodulators in MCI and changes in electroencephalogram EEG
Among the current limitations on knowledge of this disease many studies use biomarkers to predict MCI or progression to dementia and although most biomarkers are reported to be valuable in this setting few are compared with each other so this is currently difficult to understand the relative importance of the different biomarkers when used together For this reason the present project could be a contribution in the short and long term to detect changes that may or may not be related to each other and generate multiple lines of research
Population aging will continue to increase and therefore there will be a greater number of people with aMCI Currently there is no treatment that prevents the progression of aMCI to AD so the trend is to make earlier interventions aMCI is a condition of opportunity because the cognitive reserve of the patients has not been exhausted so developing studies with innovative treatments and few side effects that can change the evolution over time is important To that end understanding the etiology of this progression and designig treatments that delay or definitively stop aMCI are of importance to preserve the functionality of individuals with this condition
Clinical trials with rTMS and tDCS carried out in aMCI have already shown favorable results regarding episodic memory semantic memory and speed of information processing This trial will be able to contribute to the already reported findings that allow to identify better therapeutic approaches that support the standardization of the application of neuromodulatory techniques Besides the possible additive effect of neuromodulatory techniques and CS is well known but no studies are comparing between diferent interventions with each other The genetic characterization will be obtained an experimental biomarker of secretion proteins from olfactory epithelial neural progenitor cells together with the analysis of the neurogenic process occurring in the olfactory epithelium will be generated an experimental biomarker of serum and the effects soluble factors contained in serum on microglia will be generated neuroimaging and produce neurophysiological measures considered as possible neuroplasticity biomarkers MEPs and EEG associated with the response to non-pharmacological treatment will be recorded and evaluated if the parameters are related to clinical and cognitive characteristics With this therapeutic approach where non-invasive neuromodulatory techniques are combined with CS the aim is to improve the quality of care for patients with aMCI considering that neuromodulation alternatives can delay the process of deterioration in each patient admitted
The hypotheses in this study are 1 The combined application of non-invasive neuromodulation techniques with cognitive stimulation will significantly improve the cognitive performance of patients with aMCI compared to the single application of non-invasive neuromodulation techniques or cognitive stimulation alone 2 There will be differences in the protein expression in the olfactory epithelial neural progenitor cells of patients with aMCI who are treated with some non-invasive neuromodulation techniques and those who only receive cognitive stimulation 3 The soluble factors in the serum of patients with aMCI before and after treatment will differentially modulate microglia 4 There will be differences in brain morphology such as cortical thickness and surface area white matter integrity as well as structural connectivity between different brain areas before and after treatment with non-invasive stimulation techniques 5 There will be differences in the amplitude and latency of the MEP as well as changes in EEG of patients with aMCI who are treated with one of the non-invasive neuromodulation techniques and patients who only receive CS
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None