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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03121066
Recruitment Status : Not yet recruiting
First Posted : April 19, 2017
Last Update Posted : July 6, 2018
Consorci Sanitari de Terrassa
Information provided by (Responsible Party):
Elena Munoz Marron, Universitat Oberta de Catalunya

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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Device: Active Transcranial Magnetic Stimulation Device: Sham Transcranial Magnetic Stimulation Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The design of the study is a randomized, double blind, parallel clinical trial.
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intervention Based on Transcranial Magnetic Stimulation for Alzheimer's Disease Patients: Randomized Clinical Trial
Estimated Study Start Date : October 2018
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Experimental group
Transcranial Magnetic Stimulation + Conventional intervention
Device: Active Transcranial Magnetic Stimulation
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)
Other Name: Magstim Super Rapid 2

Sham Comparator: Sham control group
Sham Transcranial Magnetic Stimulation + Conventional intervention
Device: Sham Transcranial Magnetic Stimulation
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.
Other Name: Magstim Super Rapid 2

No Intervention: Non TMS Control group
Conventional intervention alone

Primary Outcome Measures :
  1. Change in Cognitive improvement [ Time Frame: Baseline and 1 month, 3 months and 6 months after the end of the treatment ]
    Changes in cognitive functions will be assessed through a Neuropsychological Batery

Secondary Outcome Measures :
  1. Functional capacity changes [ Time Frame: Baseline and 1 month, 3 months and 6 months after the end of the treatment ]
    Functional capacity will be assessed through the Functional Assessment Questionnaire (FAQ)

  2. Functional capacity changes [ Time Frame: Baseline and 1 month, 3 months and 6 months after the end of the treatment ]
    Functional capacity will be assessed through the UCSD Performance-Based Skills Assessment (UPSA)

  3. Mood changes [ Time Frame: Baseline and 1 month, 3 months and 6 months after the end of the treatment ]
    Mood changes will be assessed through the Hospital Anxiety and Depression Scale (HAD)

  4. Changes in brain connectivity [ Time Frame: 3 days after the end of the treatment ]
    Brain connectivity will be assessed through the registry of brain activity in the resting state Magnetic Resonance Imaging.

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Elena Munoz Marron, Principal Investigator, Universitat Oberta de Catalunya Identifier: NCT03121066     History of Changes
Other Study ID Numbers: UOCatalunya
First Posted: April 19, 2017    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Elena Munoz Marron, Universitat Oberta de Catalunya:
Transcranial Magnetic Stimulation
Non invasive brain stimulation
Theta Burst Protocol
Brain connectivity
Dorsolateral prefrontal cortex
Parietal cortex

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders