None listed
Conditions
Brief summary
Although the underlying causes of Alzheimer’s disease (Alz) remain unknown, there is clear evidence the disease process disrupts connections in brain networks underpinning cognition. Research, including our own, indicates this dysfunctional connectivity is proximate to the cognitive symptoms of Alz. Treatment approaches which have aimed to reduce disease protein burden in Alz have consistently failed to improve cognition; perhaps understandably, as none of these approaches attempt to restore dysfunctional connectivity. In contrast, we propose a therapeutic approach, using non-invasive brain stimulation, which directly targets activity in relevant neural networks in order to restore optimal connectivity and improve cognition. Theta Burst Stimulation (TBS) is an efficient and potent form of transcranial magnetic stimulation (TMS). It has been shown to modulate activity throughout large-scale cortical networks, enhance cognition and produce lasting behavioural improvements. We have conducted a proof-of-concept study demonstrating that 6-weeks of TBS applied to key regions of affected networks can alter connectivity and produce significant memory improvement in patients with mild to moderate Alz. We are now proposing to conduct a 30-week randomised controlled trial, with both acute and maintenance treatment phases and a 3 and 6-month follow up. We aim to confirm our proof-of-concept and to extend these findings by demonstrating whether standalone TBS can produce sustained gains in cognition and associated improvements in function and quality of life.
Interventions
A triple-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. 92 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 followed by a 12-week maintenance phase and a 3 and 6-month follow up. In each treatment session TBS will be sequ
A triple-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. 92 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 followed by a 12-week maintenance phase and a 3 and 6-month follow up. 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 posterior parietal cortex (lPPC, rPPC). Stimulation Parameters: All sites will be stimulated using 3-pulse 50-Hz bursts applied at 5 Hz with a 2-second train of TBS repeated every 10 seconds for a total of 180 seconds per site (i.e. 600 pulses). Therefore, stimulation for all four sites will take 12 minutes. iTBS will be applied at 100% of the RMT. TBS will be provided by a trained nurse. There will be a total of 48 TBS treatments provided.
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, 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; (2) are competent to consent based on their ability to provide a spontaneous narrative description of the key elements of the study, as assessed by an independent clinical staff member. Participants will complete an advanced care directive to allow for the possibility they may lose capacity during the trial; (3) have a diagnosis of probable Alz according to the National Institute on Aging /Alzheimer's Association diagnostic guidelines for Alzheimer's disease (NIA-AA) (4) meet criteria for mild or moderate Alz as indicated by >12 on the Mini-Mental State Evaluation; (5) are either not on a cholinesterase inhibitor or memantine or have been on a stable dose for at least 2 months prior to screening; (6) are either not on psychotropic medication or their dose of psychotropic medication has been unchanged for at least 4 weeks prior to study entry. Psychotropic medication 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; (8) are able to participate in cognitive testing in English.
Exclusion criteria
Participants will be excluded if they: (1) have a concomitant major and unstable medical, psychiatric or neurological illness or seizure disorder history; (2) are pregnant; (3) have medically implanted material that could interact with the magnetic field.
Outcome results
None listed