Enhancing Working Memory in Patients With Early Alzheimer's Disease Through the Use of rTMS

NCT ID: NCT02537496

Last Updated: 2019-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-14

Study Completion Date

2018-10-10

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

In this study the investigators aim at assessing and then enhancing neuroplasticity in the dorsolateral prefrontal cortex (DLPFC) and working memory - a key function of DLPFC - in patients with mild Alzheimer's disease (AD). The investigators will use Paired Associative Stimulation (PAS) paradigm to measure neuroplasticity and then a 4-week course of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) to the DLPFC to enhance cognitive function. Clinical and cognitive assessments will be done at baseline, one week, one month and 6 months after the rTMS course. Healthy controls will also be enrolled to carry out baseline cognitive assessments and a baseline measurement of neuroplasticity.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Specific aim 1: To assess working memory in participants with Alzheimer's disease (AD) and its change in response to a 4-week course of bilateral rTMS of DLPFC.

Hypothesis 1a: Compared to healthy individuals, participants with AD will be impaired on the N-back task.

Hypothesis 1b: Compared to sham rTMS, active rTMS will result in improvement on the N-back task in participants with AD at 1 week and 4 weeks after the treatment.

Specific aim 2: To assess DLPFC theta-gamma coupling during working memory performance in AD and its change in response to a 4-week course of bilateral rTMS of DLPFC.

Hypothesis 2a: Compared to healthy individuals, participants with AD will be impaired on DLPFC theta-gamma coupling during the N-back task.

Hypothesis 2b \& 2c: Compared to sham rTMS, active rTMS will result in improvement in DLPFC theta-gamma coupling during the N-back task in participants with AD at 1 week and 4 weeks after the treatment.

Specific aim 3: To assess DLPFC neuroplasticity using PAS in participants with AD and its change in response to a 4-week course of bilateral rTMS.

Hypothesis 3a: Compared to healthy individuals, participants with AD will be impaired on PAS-induced neuroplasticity.

Hypothesis 3b: Compared to sham rTMS, active rTMS will result in improvement on PAS-induced neuroplasticity in participants with AD at 1 week and 4 weeks after the treatment.

Specific aim 4: To assess change in working memory, theta gamma coupling and DLPFC neuroplasticity at 6 months after the course of bilateral rTMS.

Hypothesis 4: Compared to sham rTMS, active rTMS group will perform better on measures of working memory, theta gamma coupling and PAS- induced DLPFC neuroplasticity 6 months after the course of rTMS.

Specific aim 5: To assess the change in general cognitive function at 4 weeks and 6 months after the course of bilateral rTMS.

Hypothesis 5: Compared to sham rTMS, active rTMS group will perform better on measures of general cognitive function at 4 weeks and 6 months after the course of rTMS.

Specific Aim 6: To assess insight in AD at baseline and any change in insight at 4 week and 6 month post rTMS follow up. H6: Participants with AD will have impaired insight into illness and cognitive function and they will experience improved insight at 4 week and 6 month follow up points.

Specific Aim 7: To validate a new scale for insight in AD , 'The Scale to Assess Anosognosia in Neurocognitive Disorders' (SAND) for its ability to assess insight at baseline and any change at 4 weeks and 6 month follow up points. H7: In participants with AD, SAND will be able to assess insight into illness and cognitive function at baseline, and will be able to detect change in insight at follow up points.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Alzheimer's Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be assigned randomly to a 4-week repetitive course of either rTMS or control intervention (Sham rTMS) that is similar to rTMS but does not produce the same amount of brain stimulation.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Active placebo coil will be used as a Sham condition. This coil effectively mimics the real stimulation producing somatic sensation and sound (contraction of scalp muscles) with minimal direct brain effects. Same stimulation parameters and site as active condition will be used.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Alzheimer's disease rTMS

The intervention procedure done in this group is repetitive Transcranial Magnetic Stimulation.

Group Type EXPERIMENTAL

Repetitive Transcranial Magnetic Stimulation

Intervention Type PROCEDURE

Active treatment will be delivered at 90% resting motor threshold intensity. Stimulation will be administered at 20 Hz with 25 stimulation trains of 30 stimuli each with an inter-train interval of 30 sec. Treatment will be applied in sequential order bilaterally to the left and right DLPFC.

Alzheimer's disease rTMS Sham

The intervention procedure done in this group is Repetitive Transcranial Magnetic Stimulation - Sham

Group Type SHAM_COMPARATOR

Repetitive Transcranial Magnetic Stimulation - Sham

Intervention Type PROCEDURE

Same stimulation parameters and site as active condition will be used, but with placebo coil which will have minimal direct brain effects

Healthy Control

Healthy control group will only participate in baseline assessments which include baseline neuropsychological testing and baseline measurement of neuroplasticity. This will be used to standardize neuropsychological test scores and to compare the baseline neuroplasticity between healthy participants and Alzheimer's disease (AD) participants. Healthy control group will not get rTMS intervention.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Repetitive Transcranial Magnetic Stimulation

Active treatment will be delivered at 90% resting motor threshold intensity. Stimulation will be administered at 20 Hz with 25 stimulation trains of 30 stimuli each with an inter-train interval of 30 sec. Treatment will be applied in sequential order bilaterally to the left and right DLPFC.

Intervention Type PROCEDURE

Repetitive Transcranial Magnetic Stimulation - Sham

Same stimulation parameters and site as active condition will be used, but with placebo coil which will have minimal direct brain effects

Intervention Type PROCEDURE

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

rTMS rTMS - Sham

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age 55 years or above.
2. Ability to understand and speak English.
3. Confirmed Diagnosis of Probable AD by NIA-AA criteria.
4. Either not taking Cognitive enhancers or taking them at a stable dose for the last 3 months.
5. Willingness and ability to provide informed consent or an ability to assent and availability of a substitute decision maker willing to provide consent on participant's behalf.
6. Corrected visual acuity enough to read newspaper headlines.
7. Ability to hear a raised conversational voice, with hearing aids if needed.


1. Age 55 or above.
2. Willingness and ability to speak English.
3. Willingness and ability to provide informed consent.
4. Corrected visual acuity enough to read newspaper headlines.
5. Ability to hear a raised conversational voice, with hearing aids if needed.

Exclusion Criteria

1. MOCA score \< 10.
2. DSM IV - TR diagnosis of a current episode of mood disorder in the last 3 months.
3. DSM IV - TR diagnosis of a current anxiety disorder in the last 3 months.
4. DSM IV - TR diagnosis of a current substance use disorder in the last 3 months.
5. DSM IV - TR diagnosis of a current or lifetime primary psychotic disorder.
6. Diagnosis of intellectual disability or a neurodevelopmental disorder.
7. Electroconvulsive Therapy treatment in the last 6 months.
8. History of a seizure other than a febrile seizure in infancy.
9. Currently taking Anticonvulsants or Benzodiazepines.
10. Any contraindication for TMS or any other medical condition/circumstances that would make the study participation difficult for the participant.


1. Meets criteria for a DSM IV - TR diagnosis other than simple phobias or Adjustment disorder.
2. Any other neurological disorder affecting central nervous system.
3. Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
4. History of seizure other than a febrile seizure in infancy
5. Currently taking Anticonvulsants or Benzodiazepines.
6. Any contraindication for TMS or any other medical condition/circumstances that would make the study participation difficult for the participant.
Minimum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Brain & Behavior Research Foundation

OTHER

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Sanjeev Kumar

Sanjeev Kumar, MD, FRCPC

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Sanjeev Kumar, MD, FRCPC

Role: PRINCIPAL_INVESTIGATOR

Center for Addiction and Mental Health

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Center for Addiction and Mental Health

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Canada

Related Links

Access external resources that provide additional context or updates about the study.

http://www.camh.ca/en/research

Description: The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

005/2015

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.