Investigating the Effect of Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment for Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Device: rTMS sham treatmentDevice: rTMS active treatment
- Registration Number
- NCT02908815
- Lead Sponsor
- University of Manitoba
- Brief Summary
The main objective of this study is to investigate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) treatment on patients with probable early or moderate Alzheimer's disease.
- Detailed Description
Upon meeting the inclusion criteria and providing informed consent, each participant will complete a series of cognitive assessments and rTMS treatments at the TMS Lab at Riverview Health Center (PE-450).
After enrollment, patients at each site will be assigned using stratified block randomization into either active or sham treatment arms with different duration of treatment (either 2 weeks or 4 weeks).
rTMS at frequency of 20 Hz will be used to stimulate the dorsolateral prefrontal cortex (DLPFC) of each patient in the real groups. Prior to the first treatment, and once per week during treatment, the patient's motor threshold will be measured using single pulses of TMS, noting the intensity necessary to cause a small twitch in the thumb finger. Then, the 70 mm cooled coil will be placed on the head at a location for optimal stimulation of the DLPFC at an intensity of 90-100% of the motor threshold. The 20 Hz rTMS treatment will incorporate 30 pulses per train, with 25 trains per side of the brain per session (total of 750 pulses per side per session). The trains will have a duration of 1.5 seconds, with an intertrain interval of 10 seconds. Each TMS treatment session will take approximately 10 to 25 minutes.
The DLPFC will be located on each patient using our Brainsight neuronavigation system from a reference MRI scan. If we cannot retrieve a valid previous clinical MRI scan or a valid ordered research MRI scan, a reference head model will approximate the patient's anatomy.
The treatments will be administered daily (5 days/week) either for 4 weeks or 2 weeks. The same protocol will also be used while doing sham stimulation.
To prevent un-blinding, the Magstim sham coil will be used; it provides the same sound and tactile sensory experience as those of the real coil, but it attenuates the strength of the induced electrical field in the brain well below the threshold required to stimulate neurons. In addition, during the treatment, only the designated research assistant and the patient will be present. It should also be noted that the only people who know the grouping are: the rTMS administrator (who also groups the patients) at each site and the sites' coordinator. The patients' grouping info will be in a secure folder in a locked cabinet to which only the rTMS administrator and the three sites coordinator will have the key.
Participants will be assessed six times during the study. This will occur at weeks 0, 3, 5, 13, 21, and 29 for the 4 week treatment groups, and weeks 0, 3, 5, 11, 19, and 27 for the 2 week treatment group. Each assessment will involve a set of nine assessment tools, including ADAS-Cog as the primary outcome measure and various other tasks and questionnaires to measure cognition, memory, caregiver burden, symptoms, and treatment tolerability.
For Winnipeg and Montreal sites only: The immediate effects (i.e. within 3 minutes) after participants receive the rTMS treatment will be assessed with a 1-minute semantic fluency test at four time points. This will occur at before and immediately after rTMS intervention in Week 1 and at weeks 5 and 13 for the 4 week treatment groups, and before and immediately after rTMS intervention in Week 1 and at weeks 5 and 11 for the 2 week treatment group.
Patients who are randomized to the sham treatment will be unblinded at the 6 month follow up and offered either 2-weeks or 4-weeks treatment; the patients and/or their family can choose the duration of treatment. As such, the 12 month assessment will be an unblinded follow up only of those initially randomised to one of the real groups (2-weeks or 4-weeks of treatment).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 weeks sham treatment rTMS sham treatment 2 weeks of rTMS sham treatment applied using a modified rTMS coil which does not stimulate the brain. 4 weeks sham treatment rTMS sham treatment 4 weeks of rTMS sham treatment applied using a modified rTMS coil which does not stimulate the brain. 4 weeks active treatment rTMS active treatment 4 weeks of rTMS active treatment applied using an active rTMS coil. 2 weeks active treatment rTMS active treatment 2 weeks of rTMS active treatment applied using an active rTMS coil.
- Primary Outcome Measures
Name Time Method Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) change Weeks 0 and 5 Standard measure of cognitive symptoms, a popular tool that measures the severity of dementia symptoms. The primary outcome measure will be the change in the score from the baseline at 5 weeks.
- Secondary Outcome Measures
Name Time Method Verbal Fluency Test (VFT) Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Fluency test where the participant has to name as many words a possible that match a certain criteria.
Neuropsychiatric Inventory-Questionnaire (NPI-Q) Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Caregiver questionnaire that assesses severity of symptoms
Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Caregiver questionnaire that assesses patient's ability to handle daily activities
Clinical Dementia Rating (CDR) sum of boxes Week 27 for the 2 week group and week 29 for the 4 week group Assesses the severity of cognitive and functional decline related to Alzheimer's disease and other dementias
Digit Span Test Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Memory test asking the participant to remember a sequence of numbers and repeat them back.
Zarit Burden Interview (ZBI) Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Caregiver questionnaire that assesses the burden of the patient on the caregiver
Stroop Test Weeks 0, 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Measures a person's attention by having them read colour names when the colour of the text doesn't match.
Treatment Satisfaction Questionnaire for Medication (TSQM) Weeks 3, 5, 11, 19, and 27 for the 2 week group and weeks 0, 3, 5, 13, 21, and 29 for the 4 week groups Assessment that asks directly if the participant is satisfied with the treatment
Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) effect over time Weeks 0, 3, 11, 19, and 27 for the 2 week group and weeks 0, 3, 13, 21, and 29 for the 4 week groups Standard measure of cognitive symptoms, a popular tool that measures the severity of dementia symptoms.
Semantic Fluency Test (SFT) Before and immediately after rTMS intervention in Week 1, at weeks 5 and 11 for the 2 week group and before and immediately after rTMS intervention in Week 1, at weeks 5, and 13 for the 4 week groups Fluency test where the participant has to name as many animals in 1 minute (Winnipeg and Montreal sites only)
Trial Locations
- Locations (3)
McGill University
🇨🇦Montreal, Quebec, Canada
Monash University
🇦🇺Melbourne, Victoria, Australia
Riverview Health Center
🇨🇦Winnipeg, Manitoba, Canada