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Transcranial Magnetic Stimulation for Alzheimer's Disease Treatment (TMSAD)

Primary Purpose

Alzheimer Disease

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Active Transcranial Magnetic Stimulation
Sham Transcranial Magnetic Stimulation
Sponsored by
Universitat Oberta de Catalunya
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Transcranial Magnetic Stimulation, Non invasive brain stimulation, Theta Burst Protocol, Brain connectivity, Dorsolateral prefrontal cortex, Parietal cortex

Eligibility Criteria

60 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of Alzheimer's disease according to the diagnostic criteria of the National Institute on Ageing and the Alzheimer's Association
  • Ages between 60 and 75 years
  • Mini Mental State Examination score between 20 and 26
  • Global Deterioration Scale score of 3 or 4
  • Functional independence for basic daily life activities (part C of the Blessed Scale equal or 0)
  • Rosen Ischemia Scale less or equal to 4
  • Able to read and write
  • Stable medical and pharmacological state during the 3 consecutive months immediately before the start of the study
  • Computed Tomography Scan and Magnetic Resonance Imaging in the last 12 months previous to the selection, compatible with the diagnosis of probable Alzheimer's disease in the subjects diagnosed
  • Absence of clinically significant anomalies in the medical history or clinical laboratory results during the selection
  • Screening analyses within normal range with the objective of detecting and excluding other causes of dementia in the last 12 months previous to selection. Laboratory values required in order to be considered within the normal range are as follows: complete blood count, thyroid hormones, T4, folic acid, vitamin B12, albumin, transaminase alanine, amino-transferase aspartate, gamma-glutamic transferase, sodium, potassium, urea, creatinine, glucose while fasting
  • Being treated by Acetylcholinesterase Inhibitors
  • Signed consent form, previously approved by the Research Ethics Committee

Exclusion Criteria:

  • Knowledge of Spanish or Catalan after the age of 15
  • Less than 4 years of schooling
  • Intellectual deficiency (Premorbid Intelligence Quotient, vocabulary, less than 85)
  • Not controlled medical conditions or severe mental disorders that may affect the Central Nervous System, including signs of increased intracranial pressure or intracranial lesions
  • Presenting one or more vascular risks
  • Medical conditions not controlled that may cause medical emergencies in case the produce convulsions (expel: cardiac malformations, cardiac arrhythmias, asthma, etc.)
  • Medical history of convulsions, previous diagnosis of epilepsy, previous registry of abnormal electroencephalogram or family history of epilepsy
  • Severe hearing problems or ringing in the ears (tinnitus)
  • Severe loss of visual acuity
  • Moderate or severe depression according to a score >11 (moderate depression) or 19 (severe depression) in the Geriatric Depression Scale
  • Presence of tremors or motor control of the dominant upper extremity
  • Being under pharmacological treatment with medications indicated in the security guidelines.
  • Drug or alcohol consumption or history of abuse in the last 24 months prior to the study
  • Implants of metal pieces in the brain (excluding dental fillings)
  • Either of the following medical devices: pacemaker, implanted medication pumps, vagal nerve stimulators, deep cerebral stimulators, transcutaneous electrical stimulation units, ventriculus-peritoneal derivations, titanium plates, cochlear implants, aneurysm clips, etc…
  • Negative response towards new technology
  • Existence of any situation that may cause the subject, according to the principal researcher, not be an adequate candidate for the study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Active Comparator

    Sham Comparator

    No Intervention

    Arm Label

    Experimental group

    Sham control group

    Non TMS Control group

    Arm Description

    Transcranial Magnetic Stimulation + Conventional intervention

    Sham Transcranial Magnetic Stimulation + Conventional intervention

    Conventional intervention alone

    Outcomes

    Primary Outcome Measures

    Change in Cognitive improvement
    Changes in cognitive functions will be assessed through a Neuropsychological Batery

    Secondary Outcome Measures

    Functional capacity changes_1
    Functional capacity will be assessed through the Functional Assessment Questionnaire (FAQ)
    Functional capacity changes_2
    Functional capacity will be assessed through the UCSD Performance-Based Skills Assessment (UPSA)
    Mood changes
    Mood changes will be assessed through the Hospital Anxiety and Depression Scale (HAD)
    Changes in brain connectivity
    Brain connectivity will be assessed through the registry of brain activity in the resting state Magnetic Resonance Imaging.

    Full Information

    First Posted
    April 1, 2017
    Last Updated
    November 8, 2022
    Sponsor
    Universitat Oberta de Catalunya
    Collaborators
    Consorci Sanitari de Terrassa
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03121066
    Brief Title
    Transcranial Magnetic Stimulation for Alzheimer's Disease Treatment
    Acronym
    TMSAD
    Official Title
    Intervention Based on Transcranial Magnetic Stimulation for Alzheimer's Disease Patients: Randomized Clinical Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2023 (Anticipated)
    Primary Completion Date
    September 2024 (Anticipated)
    Study Completion Date
    December 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Universitat Oberta de Catalunya
    Collaborators
    Consorci Sanitari de Terrassa

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. Study Description

    Brief Summary
    Background: Alzheimer's disease is a major health problem in our society. To date, pharmacological treatments to reduce Alzheimer's disease symptoms have obtained poor results and there is a growing interest in finding non-pharmacological treatments for this impactful disease. Transcranial Magnetic Stimulation is a non-invasive tool which can induce changes in brain activity and long term modifications of impaired neural networks, and therefore holds promise as a clinical intervention. Our overall goal is to study the benefit of targeting Transcranial Magnetic Stimulation based on the individual's unique functional connectivity (personalized targeting) instead of current non-individualized approaches. Specifically, the intermittent Theta Burst protocol will be used and changes in cognitive, functional, and emotional deficits in these patients will be evaluated. Functional brain connectivity changes induced by the TMS treatment will be also assessed. Methods: A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, one month, three months and six months after the end of the treatment in comparison to the baseline measurements. Forty-five patients with a diagnosis of Alzheimer's disease, will be randomly allocated (1:1:1) into experimental (active Transcranial Magnetic Stimulation), sham control group, or conventional intervention control group. Neuropsychological, functional, and emotional assessment will be conducted, as well as functional connectivity measures, in order to assess the effectiveness of the treatment. Discussion: The investigators expect to demonstrate that personalized Transcranial Magnetic Stimulation intervention has measurable positive impact in cognitive and emotional functioning, functionality, and brain connectivity, thus representing a potential treatment for Alzheimer's disease.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Alzheimer Disease
    Keywords
    Transcranial Magnetic Stimulation, Non invasive brain stimulation, Theta Burst Protocol, Brain connectivity, Dorsolateral prefrontal cortex, Parietal cortex

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Model Description
    The design of the study is a randomized, double blind, parallel clinical trial.
    Masking
    ParticipantOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    45 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Experimental group
    Arm Type
    Active Comparator
    Arm Description
    Transcranial Magnetic Stimulation + Conventional intervention
    Arm Title
    Sham control group
    Arm Type
    Sham Comparator
    Arm Description
    Sham Transcranial Magnetic Stimulation + Conventional intervention
    Arm Title
    Non TMS Control group
    Arm Type
    No Intervention
    Arm Description
    Conventional intervention alone
    Intervention Type
    Device
    Intervention Name(s)
    Active Transcranial Magnetic Stimulation
    Other Intervention Name(s)
    Magstim Super Rapid 2
    Intervention Description
    The intervention consists of a 2-week treatment during which TMS will be applied for 10 days (every working day). The stimulation protocol will be intermittent TBS (iTBS). 600 pulses in each area will be applied at intervals of 2 seconds of stimulation and 8 seconds of rest; the total number of pulses per session will be 1200. The stimulation duration is 3 minutes and 12 seconds. This protocol allows the induction of long-term potentiation effects, promoting plasticity in the stimulated areas. To perform the stimulation a 70 mm, figure of 8-coil will be used. In order to precisely locate the stimulated areas a stereotactic image guidance will be used during the stimulation (Brainsight™ 2)
    Intervention Type
    Device
    Intervention Name(s)
    Sham Transcranial Magnetic Stimulation
    Other Intervention Name(s)
    Magstim Super Rapid 2
    Intervention Description
    The Sham intervention will be carried out using the same stimulation protocol as in the active condition but with the coil rotated 90º to prevent the magnetic field inducing electrical activity in the cortex.
    Primary Outcome Measure Information:
    Title
    Change in Cognitive improvement
    Description
    Changes in cognitive functions will be assessed through a Neuropsychological Batery
    Time Frame
    Baseline and 1 month, 3 months and 6 months after the end of the treatment
    Secondary Outcome Measure Information:
    Title
    Functional capacity changes_1
    Description
    Functional capacity will be assessed through the Functional Assessment Questionnaire (FAQ)
    Time Frame
    Baseline and 1 month, 3 months and 6 months after the end of the treatment
    Title
    Functional capacity changes_2
    Description
    Functional capacity will be assessed through the UCSD Performance-Based Skills Assessment (UPSA)
    Time Frame
    Baseline and 1 month, 3 months and 6 months after the end of the treatment
    Title
    Mood changes
    Description
    Mood changes will be assessed through the Hospital Anxiety and Depression Scale (HAD)
    Time Frame
    Baseline and 1 month, 3 months and 6 months after the end of the treatment
    Title
    Changes in brain connectivity
    Description
    Brain connectivity will be assessed through the registry of brain activity in the resting state Magnetic Resonance Imaging.
    Time Frame
    3 days after the end of the treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    60 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Diagnosis of Alzheimer's disease according to the diagnostic criteria of the National Institute on Ageing and the Alzheimer's Association Ages between 60 and 75 years Mini Mental State Examination score between 20 and 26 Global Deterioration Scale score of 3 or 4 Functional independence for basic daily life activities (part C of the Blessed Scale equal or 0) Rosen Ischemia Scale less or equal to 4 Able to read and write Stable medical and pharmacological state during the 3 consecutive months immediately before the start of the study Computed Tomography Scan and Magnetic Resonance Imaging in the last 12 months previous to the selection, compatible with the diagnosis of probable Alzheimer's disease in the subjects diagnosed Absence of clinically significant anomalies in the medical history or clinical laboratory results during the selection Screening analyses within normal range with the objective of detecting and excluding other causes of dementia in the last 12 months previous to selection. Laboratory values required in order to be considered within the normal range are as follows: complete blood count, thyroid hormones, T4, folic acid, vitamin B12, albumin, transaminase alanine, amino-transferase aspartate, gamma-glutamic transferase, sodium, potassium, urea, creatinine, glucose while fasting Being treated by Acetylcholinesterase Inhibitors Signed consent form, previously approved by the Research Ethics Committee Exclusion Criteria: Knowledge of Spanish or Catalan after the age of 15 Less than 4 years of schooling Intellectual deficiency (Premorbid Intelligence Quotient, vocabulary, less than 85) Not controlled medical conditions or severe mental disorders that may affect the Central Nervous System, including signs of increased intracranial pressure or intracranial lesions Presenting one or more vascular risks Medical conditions not controlled that may cause medical emergencies in case the produce convulsions (expel: cardiac malformations, cardiac arrhythmias, asthma, etc.) Medical history of convulsions, previous diagnosis of epilepsy, previous registry of abnormal electroencephalogram or family history of epilepsy Severe hearing problems or ringing in the ears (tinnitus) Severe loss of visual acuity Moderate or severe depression according to a score >11 (moderate depression) or 19 (severe depression) in the Geriatric Depression Scale Presence of tremors or motor control of the dominant upper extremity Being under pharmacological treatment with medications indicated in the security guidelines. Drug or alcohol consumption or history of abuse in the last 24 months prior to the study Implants of metal pieces in the brain (excluding dental fillings) Either of the following medical devices: pacemaker, implanted medication pumps, vagal nerve stimulators, deep cerebral stimulators, transcutaneous electrical stimulation units, ventriculus-peritoneal derivations, titanium plates, cochlear implants, aneurysm clips, etc… Negative response towards new technology Existence of any situation that may cause the subject, according to the principal researcher, not be an adequate candidate for the study

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    30185210
    Citation
    Marron EM, Viejo-Sobera R, Quintana M, Redolar-Ripoll D, Rodriguez D, Garolera M. Transcranial magnetic stimulation intervention in Alzheimer's disease: a research proposal for a randomized controlled trial. BMC Res Notes. 2018 Sep 5;11(1):648. doi: 10.1186/s13104-018-3757-z.
    Results Reference
    derived

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