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
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
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
NCT ID
NCT03121066
First Posted
April 1, 2017
Last Updated
November 8, 2022
Sponsor
Universitat Oberta de Catalunya
Collaborators
Consorci Sanitari de Terrassa
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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Transcranial Magnetic Stimulation for Alzheimer's Disease Treatment
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