None listed
Conditions
Brief summary
Memory problems in Alzheimer's disease (AD) are linked to disruptions in the connections between brain regions. In a recent study we demonstrated that Theta Burst Stimulation (TBS), a type of brain stimulation, can alter the connections between brain regions and improve memory in patients with AD. We now propose a randomised controlled trial to examine whether TBS can lead to lasting improvements in 168 individuals with mild to moderate AD. We plan to compare active vs sham (placebo) TBS. Treatment will involve a 6-weeks of daily treatment (Monday – Friday) followed by a 6-weeks of once-weekly treatment. Treatment will be individualised for each participant. This means that stimulation will be based on the individual participant’s brain activity, recorded using electroencephalography (EEG). Additionally, the treatment will be delivered to four areas of the brain, the locations of which will be identified for each participant using a brain scan: a functional magnetic resonance imaging (fMRI) scan. We will examine changes in brain activity, memory and other symptoms of AD before and after treatment, as well as at 3, 6, and 12 month follow ups. If effective, individualised TBS could be used as a new therapy for AD.
Interventions
A double-blind placebo-controlled clinical trial comparing a course of active theta burst stimulation (TBS) (an efficient and potent form of transcranial magnetic stimulation (TMS)) to sham TBS. Participants with mild to moderate Alz will be randomised to 1 of 2 conditions (active TBS vs sham TBS) in a 1 to 1 allocation ratio. The treatment course will involve a 6-week acute phase (daily treatments Mon-Fri) followed by a 6-week maintenance phase (once weekly treatment) and 3, 6 and 12-month foll
A double-blind placebo-controlled clinical trial comparing a course of active theta burst stimulation (TBS) (an efficient and potent form of transcranial magnetic stimulation (TMS)) to sham TBS. Participants with mild to moderate Alz will be randomised to 1 of 2 conditions (active TBS vs sham TBS) in a 1 to 1 allocation ratio. The treatment course will involve a 6-week acute phase (daily treatments Mon-Fri) followed by a 6-week maintenance phase (once weekly treatment) and 3, 6 and 12-month follow ups. In each treatment session TBS will be sequentially provided to four brain regions, the left and right dorsolateral prefrontal cortex (lDLPFC, rDLPFC) and the left and right inferior parietal lobule (lIPL, rIPL). Stimulation Parameters: Stimulation will be provided using a MagVenture Magpro30 (MagVenture, Lucerne, Denmark) magnetic stimulator with a butterfly figure-of-8 coil (MagVenture Cool-B65 coil). All four brain sites will be stimulated using an individualised intermittent TBS protocol. Specifically, all sites will be stimulated using 3-pulse individualised gamma-Hz bursts applied at individualised theta-Hz with a 2-second train of TBS repeated every 10 seconds for a total of 180 seconds per site (i.e., approximately 600 pulses). Stimulation of all four sites will take 12 minutes per treatment session. Treatment sessions, including setup and coil repositioning, will be no longer than 30 minutes in total. iTBS will be applied at 100% of the Resting Motor Threshold and all treatments will be provided by a trained TMS clinician. There will be a total of 36 iTBS treatments provided over a 12 week period. Treatment adherence will be recorded by TMS clinicians via the use of session attendance checklists. Individualised stimulation parameters will be obtained via EEG and fMRI which will be collected during the baseline assessments, which will occur within a two week window prior to treatment commencement.
Sponsors
Bionics Institute of Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Participants will be included if they: (1) are between 50 and 85 years of age; (2) have a diagnosis of 'probable Alzheimer's disease (AD) dementia' according to the National Institute on Aging/Alzheimer's Association diagnostic guidelines of AD (NIA-AA) (3) meet criteria for mild or moderate AD as indicated by a score >12 on the Mini-Mental State Evaluation; (4) are competent to consent based on their ability to provide a spontaneous narrative description of the key elements of the study, or, if they are unable to consent, consent may be provided on their behalf by a legally authorized representative, who may be a family member, legal guardian, or other designated representative as consistent with the relevant state and federal legislation applicable for each study site. Where participants can consent an advance care directive will be taken, whereby if they lose capacity to consent during the trial they can choose to either withdraw or for consent to be sought from their legally authorized representative. In all instances where consent is provided by the participant's legally authorized representative, the participant's willingness to participate (i.e., assent) will be required and documented. (5) are either not on a cholinesterase inhibitor and/or memantine or have been on a stable dose for at least 3 months prior to screening; (6) are either not on a psychotropic medication or their dose of psychotropic medication has been unchanged for at least 4 weeks prior to study entry. Psychotropic dose will not be able to be altered during the trial: if this is clinically required the participant will be withdrawn; (7) have frequent contact with a close other who can provide information on the participant's cognitive and functional abilities.
Exclusion criteria
Participants will be excluded if they: (1) have a concomitant major and unstable medical, psychiatric, or neurological illness or seizure disorder history; (3) are pregnant; (3) have medically implanted material that could interact with the magnetic field (relevant for Magnetic Resonance Imaging and Transcranial Magnetic Stimulation).
Outcome results
None listed