Comparison of Two Non-invasive Neuromodulation Techniques as Synergistic Therapy to Cognitive Stimulation in Amnestic Mild Cognitive Impairment (aMCI)

NCT06467253 | Recruiting

• 1 other identifier: IC20137.0
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment

Keywords

Mild cognitive impairment; Repetitive Transcranial Magnetic Stimulation rTMS; Transcranial Direct Current Stimulation tDCS; Neuromodulation Techniques; Amnestic Mild Cognitive Impairment; Cognitive Stimulation

Outcome Measures

Primary Outcomes (24)

• Changes in orientation

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in language

  Measured by the WAIS-IV vocabulary test. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in language

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in verbal memory

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in verbal memory

  Measured by Neuropsi Attention and Memory. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in visual memory

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in visual memory

  Measured by Neuropsi Attention and Memory. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in visual-constructive abilities

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in visual-constructive abilities

  Measured by Neuropsi Attention and Memory. Score ranges from 10 or less to 95. Direct scores are converted to standardized scores. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in processing speed

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in processing speed

  Measured by the Trail Making Test version A and B. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in abstraction

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in verbal fluency

  Measured by a verbal fluency test (semantic: animals and phonologic: F, A, S). Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in interference

  Measured by the Stroop Test. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in working memory

  Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in working memory

  Measured by Trail Making Test version A and B. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes.

  Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).

• Changes in Global Cognitive Function

  Measured by Montreal Cognitive Assessment. Score ranges from 0 to 30 points. Higher scores mean better outcomes.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Global Cognitive Function

  Measured by Screen for Cognitive Impairment in Psychiatry. Direct scores ranges from 37 to 115 points. Higher scores mean better outcomes.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in memory regarding situations and activities of daily life

  Measure by Everyday Memory Questionnaire. Score ranges from 0 to 56. Higher scores mean worse outcomes.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later)

• Changes in Global Clinical Impression

  Measure by Clinical Impression Scale. Score ranges from 0 to 7. Higher scores mean worse outcomes.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Motor Evoked Potentials

  Measured by MagVenture, Transcranial Magnetic Stimulation (TMS). Evaluation of cortical excitability and synaptic plasticity using a 5 Hz-rMTS (repetitive TMS). Increased amplitude and decreased latency parameters mean better outcomes after the intervention.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Olfactory Epithelial Neural Progenitor Cells

  Measured by Neural Progenitor Cells Isolated. Quantification of the number of neural progenitor cells isolated from the olfactory epithelium. Increased number of neural progenitor cells after the intervention.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Solubles Factors of Serum

  Measured by Exosome Analysis.To find a differential content of inflammatory markers in the exosomes before and after the intervention.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Functional Magnetic Resonance Imaging

  Measured by Philips Magnetic Resonator, Ingenia 3T Equipment. The Sternberg task, which stimulates working memory and recent memory, will be used to observe changes Bold signal changes in gray matter, the hippocampus and white matter tracts.

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

Secondary Outcomes (5)

• Changes in Apathy symptoms

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in Depression

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in behavioral and psychological symptoms

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in electroencephalogram

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

• Changes in smell identification

  Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).

Study Arms (4)

1. rTMS + CS

ACTIVE COMPARATOR

Repetitive Transcranial Magnetic Stimulation (rTMS) + Cognitive Stimulation (CS)

Device: 1. rTMS + CS

2. rTMS Sham + CS

SHAM COMPARATOR

Repetitive Transcranial Magnetic Stimulation Sham (rTMS Sham) + Cognitive Stimulation (CS)

Device: 2. rTMS Sham + CS

3. tDCS + CS

ACTIVE COMPARATOR

Transcranial Direct Current Stimulation (tDCS) + Cognitive Stimulation (CS)

Device: 3. tDCS + CS

4. tDCS Sham + CS

SHAM COMPARATOR

Transcranial Direct Current Stimulation Sham (tDCS Sham) + Cognitive Stimulation (CS)

Device: 4. tDCS Sham + CS

Interventions

1. rTMS + CS DEVICE

In the first phase each participant will receive 15 sessions of rTMS and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of rTMS and 1 session of CS per week for 12 weeks. Each session will consist of 10 trains of 10 stimuli, at a 5-Hz frequency and a stimulation intensity of 120% of the resting motor threshold. rTMS will be administered by a MagPro R30 stimulator (MagVenture) and an active/placebo 8-shape coil model MCF-B70. Two surface electrodes will be employed to replicate rTMS skin sensations near the stimulation site. The rTMS condition will be double-blinded through the use of a USB stick. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of rTMS and 21 sessions of CS.

1. rTMS + CS

2. rTMS Sham + CS DEVICE

In the first phase each participant will receive 15 sessions of rTMS Sham and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of Sham rTMS and 1 session of CS per week for 12 weeks. In total, each participant will receive 27 sessions of Sham rTMS and 21 sessions of CS. rTMS will be administered by a MagPro R30 stimulator (MagVenture) and an active/placebo 8-shape coil model MCF-B70. Two surface electrodes will be employed to replicate rTMS skin sensations near the stimulation site. The sham condition will be double-blinded through the use of a USB stick. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of rTMS and 21 sessions of CS.

2. rTMS Sham + CS

3. tDCS + CS DEVICE

In the first phase each participant will receive 15 sessions of tDCS and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of tDCS and 1 session of CS per week for 12 weeks. Each session will consist of the delivery of a weak direct current of 2mA for 30 minutes. tDCS will be administered by the Sooma tDCS stimulator. The tDCS condition will be double-blinded, and a third operator will program the stimulator. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of tCDS and 21 sessions of CS.

3. tDCS + CS

4. tDCS Sham + CS DEVICE

In the first phase each participant will receive 15 sessions of tDCS Sham and 9 sessions of CS divided in 3 weeks, in the maintenance phase each participant will receive 1 session of Sham tDCS and 1 session of CS per week for 12 weeks. tDCS will be administered by the Sooma tDCS stimulator. The sham condition will be double-blinded, and a third operator will program the stimulator. Cognitive stimulation will be a Mexican adaptation of the "Memory Training and Cognitive Stimulation for Mild Cognitive Impairment" from the Center for the Prevention of Cognitive Impairment of the Madrid City Council. In total, each participant will receive 27 sessions of Sham tDCS and 21 sessions of CS.

4. tDCS Sham + CS

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Being vaccinated against the SARS-COV2 virus.
• Speak Spanish fluently.
• Level of schooling greater than or equal to 6 years.
• Amnestic mild cognitive impairment established by clinical examination performed by the treating physician (MoCA score: 19-25 points for probable aMCI) (based on the National Institute on Aging and Alzheimer's Association (NIA/AA) criteria, 2011).
• Adequate visual and auditory acuity to perform neuropsychological tests and cognitive rehabilitation.
• If receiving psychotropic drugs, having started the drugs at least 12 weeks before the start of the study, remaining at stable doses, or having suspended the drugs for at least 4 weeks before the study.
• Be in good health without non-psychiatric medical diseases (uncontrolled systemic arterial hypertension, diabetes mellitus or dyslipidemia, infections, thyroid disease, vitamin deficiency) interfering with the study.
• Willingness to participate in a study scheduled for 8 weeks and that participants can go to the Instituto Nacional De Psiquiatría for treatments, as well as scheduled evaluations.
• An informant to respond to some of the assessment questionnaires throughout the study and who would stay with the participant for at least 10 h/week.

You may not qualify if:

• Any neurological disease that raises suspicion of cognitive failure other than Alzheimer's disease, such as Parkinson's, multi-infarct dementia, Huntington's disease, hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, history of trauma craniocerebral with loss of alertness.
• Participants with a history of severe psychiatric disorders according to DSM-5 (bipolar disorder, schizophrenia, chronic depression) or with psychotic features, agitation, or behavioral problems in the last three months that could lead to difficulties in meeting the protocol.
• History of psychoactive substance abuse and current alcohol consumption with a pattern of abuse or dependence in the last two years.
• Participants with alterations in a conventional electroencephalogram (paroxysmal phenomena identified by a neurophysiologist).
• Participants with pacemakers, intracranial metal objects, or history of brain surgery, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body.
• Participation in the last 6 months in a clinical study that involved neuropsychological assessment.

Sponsors & Collaborators

• Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente: lead

Study Sites (1)

Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

Mexico City, 14370, Mexico

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Ruth Alcalá Lozano, Dr.

  Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ruth Alcalá Lozano, Dr.

CONTACT

5541605065; ruthalcala@inprf.gob.mx

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Comparative, double-blind, randomized controlled clinical trial.

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: June 20, 2024
• Study Start: June 1, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: June 20, 2024

Record last verified: 2024-06

Locations

ME (1)