NCT03121066

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.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
45

participants targeted

Target at P25-P50 for not_applicable alzheimer-disease

Timeline
Completed

Started Nov 2023

Shorter than P25 for not_applicable alzheimer-disease

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 1, 2017

Completed
18 days until next milestone

First Posted

Study publicly available on registry

April 19, 2017

Completed
6.5 years until next milestone

Study Start

First participant enrolled

November 1, 2023

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2024

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2024

Completed
Last Updated

November 9, 2022

Status Verified

November 1, 2022

Enrollment Period

10 months

First QC Date

April 1, 2017

Last Update Submit

November 8, 2022

Conditions

Alzheimer Disease

Keywords

Transcranial Magnetic StimulationNon invasive brain stimulationTheta Burst ProtocolBrain connectivityDorsolateral prefrontal cortexParietal cortex

Outcome Measures

Primary Outcomes (1)

  • Change in Cognitive improvement

    Changes in cognitive functions will be assessed through a Neuropsychological Batery

    Baseline and 1 month, 3 months and 6 months after the end of the treatment

Secondary Outcomes (4)

  • Functional capacity changes_1

    Baseline and 1 month, 3 months and 6 months after the end of the treatment

  • Functional capacity changes_2

    Baseline and 1 month, 3 months and 6 months after the end of the treatment

  • Mood changes

    Baseline and 1 month, 3 months and 6 months after the end of the treatment

  • Changes in brain connectivity

    3 days after the end of the treatment

Study Arms (3)

Experimental group

ACTIVE COMPARATOR

Transcranial Magnetic Stimulation + Conventional intervention

Device: Active Transcranial Magnetic Stimulation

Sham control group

SHAM COMPARATOR

Sham Transcranial Magnetic Stimulation + Conventional intervention

Device: Sham Transcranial Magnetic Stimulation

Non TMS Control group

NO INTERVENTION

Conventional intervention alone

Interventions

Active Transcranial Magnetic StimulationDEVICE

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)

Also known as: Magstim Super Rapid 2
Experimental group
Sham Transcranial Magnetic StimulationDEVICE

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.

Also known as: Magstim Super Rapid 2
Sham control group

Eligibility Criteria

Age60 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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…
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (1)

  • 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.

    PMID: 30185210DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: The design of the study is a randomized, double blind, parallel clinical trial.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 1, 2017

First Posted

April 19, 2017

Study Start

November 1, 2023

Primary Completion

September 1, 2024

Study Completion

December 1, 2024

Last Updated

November 9, 2022

Record last verified: 2022-11

Data Sharing

IPD Sharing
Will not share