Alzheimer's DiseaseTMS-ADNCT01847586
Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease
A study testing Paired Associative Stimulation in people with Alzheimer's Disease, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
The purpose of this study is to determine if a novel brain stimulation approach using magnetic stimulation (Transcranial Magnetic Stimulation [TMS]) can improve memory and thinking processes in individuals with mild Alzheimer's disease (AD). Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease
- What is being tested?
- Paired Associative Stimulation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2013to Oct 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Age 65 or above
- Meet NINCDS-ADRDA and DSM-IV TR criteria for a current diagnosis of Alzheimer's Disease
- Stable does of acetylcholinesterase inhibitors for at least 3 months
- Willingness and ability to speak English
- Willingness and ability to provide informed consent
- Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
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- Age 65 or above
- Willingness and ability to speak English
- Willingness and ability to provide informed consent
- Corrected visual ability that enables reading of newspaper headlines and corrected hearing capacity that is adequate to respond to a raised conversational voice.
Who cannot join
- Meets criteria for an Axis I diagnosis within the past 12 months other than Dementia of the Alzheimer type.
- Mini Mental Status Examination score of 16 or less as described above
- Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
- Electroconvulsive Therapy (ECT) within 6 months of testing.
- Left handedness.
- Incompetency to consent
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- Any contraindication for TMS
- Meets criteria for an Axis I diagnosis other than simple phobias or adjustment disorder.
- Other neurological disorder affecting central nervous system.
- Psychotropic medication except for sedative /hypnotics at a stable dose for at least 4 weeks.
- Left handedness
- Any contraindication for TMS
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine if a novel brain stimulation approach using magnetic stimulation (Transcranial Magnetic Stimulation [TMS]) can improve memory and thinking processes in individuals with mild Alzheimer's disease (AD).
Read the detailed description
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 AD. The investigators will use a novel non-invasive brain stimulation approach, Paired Associative Stimulation (PAS). PAS simulates in humans the induction of long-term potentiation (LTP), a prototype of synaptic neuroplasticity. PAS involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC. As such, these two stimulations arrive simultaneously in the DLPFC and result in potentiation of TMS induced cortical evoked potential, analogous to in vitro LTP.
Specific Aim 1: To compare LTP in the DLPFC among patients with mild AD and healthy subjects.
Specific Aim 2: To assess the effect of a 2-week course of PAS (rPAS) as applied to the left DLPFC on LTP and performance on working memory in patients with mild AD in comparison with a 2-week course of PAS control condition (PAS-C, described below) (rPAS-C).
- Conditions
- Alzheimer's Disease
- Being tested
- Paired Associative Stimulation, Paired Associative Stimulation-Control
- Keywords
- Alzheimer's Disease, Brain stimulation, transcranial magnetic stimulation
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paired Associative StimulationProcedure or surgery
PAS simulates in humans the induction of long-term potentiation (LTP), a prototype of synaptic neuroplasticity. PAS involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC. As such, these two stimulations arrive simultaneously in the DLPFC and result in potentiation of TMS induced cortical evoked potential, analogous to in vitro LTP.
Paired Associative Stimulation-ControlProcedure or surgery
PAS-C is a control PAS paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP.
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's disease-rPAS | Experimental | The intervention procedure will done in this group is r-Paired Associative Stimulation. This involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC Receives: Procedure: Paired Associative Stimulation |
| Alzheimer's disease-rPAS-C | Placebo comparator | The intervention procedure being done with this group is PAS-C. This is a control Paired Associative Stimulation paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP. Receives: Procedure: Paired Associative Stimulation-Control |
| Control | Other | Controls will have a one time Paired Associative Stimulation-Control (PAS-C) paradigm intervention in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP. Receives: Procedure: Paired Associative Stimulation-Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Paired Associated Stimulation induced Long-term potentiation as a measure of neuroplasticity in the dorsolateral prefrontal cortex
We are using a novel technique of TMS- EEG as developed by our group. Through this technique, not only motor evoked potential (MEP) but also cortical evoked activity (CEA) is recorded continuously while TMS is being delivered to the cortex. Thus, PAS-induced LTP could be indexed through the potentiation of not only MEP but also of CEA. TMS-EEG has been used by our group and others. Our group has used TMS-EEG in healthy individuals and patients with severe mental illness to study several neurophysiological phenomena in M1 and DLPFC such as cortical inhibition, gamma oscillations, and recently LTP.
In summary, we propose to combine PAS with TMS-EEG to assess DLPFC neuroplasticity in patients with mild AD and then deliver a 2-week course of daily repetitive PAS (rPAS) to enhance DLPFC neuroplasticity and function as indexed by the N-back task. This will be measured to see if there are any changes after 1 day, 7 days and 14 days of the intervention procedure.
Measured: 14 days
Secondary outcomes (1)
N-back Task
Working Memory Assessment: Participants will have their working memory assessed pre- and 1, 7, and 14 days post intervention using the N-back task. In the N-back task participants determine whether a stimulus is the same as that presented N trials back. One and 7 days post-intervention, the N-back task will be administered to assess the short- and long-term effect of rPAS on working memory as our preliminary data demonstrate a long-term enhancing effect of PAS on motor learning
Measured: pre-intervention (baseline) and then 1, 7, 14 days after intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2013 (estimated)
- Study startApr 2013
- Primary completionOct 2016
- Study completionOct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tarek Rajji, Centre for Addiction and Mental Health
- Investigators
- Tarek Rajji, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01847586
- Sponsor's protocol ID
- 215/2012
- Acronym
- TMS-AD
- Status last verified
- Jan 2018
- First submitted
- 26 Apr 2013
- Last updated
- 24 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Kumar S, Zomorrodi R, Ghazala Z, Goodman MS, Blumberger DM, Daskalakis ZJ, Fischer CE, Mulsant BH, Pollock BG, Rajji TK. Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer's disease: a pilot randomized double-blind-controlled trial. Int Psychogeriatr. 2023 Mar;35(3):143-155. doi: 10.1017/S1041610220003518. Epub 2020 Nov 16.
PubMed 33190659
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Neuroplasticity and Frontal Lobe Function in Patients With Mild Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT01847586
- Acronym / sponsor ID
- TMS-AD / 215/2012
- Conditions
- Alzheimer's Disease
- Keywords
- Alzheimer's Disease, Brain stimulation, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Oct 2016 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 7 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine if a novel brain stimulation approach using magnetic stimulation (Transcranial Magnetic Stimulation [TMS]) can improve memory and thinking processes in individuals with mild Alzheimer's disease (AD).
Detailed description
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 AD. The investigators will use a novel non-invasive brain stimulation approach, Paired Associative Stimulation (PAS). PAS simulates in humans the induction of long-term potentiation (LTP), a prototype of synaptic neuroplasticity. PAS involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC. As such, these two stimulations arrive simultaneously in the DLPFC and result in potentiation of TMS induced cortical evoked potential, analogous to in vitro LTP.
Specific Aim 1: To compare LTP in the DLPFC among patients with mild AD and healthy subjects.
Specific Aim 2: To assess the effect of a 2-week course of PAS (rPAS) as applied to the left DLPFC on LTP and performance on working memory in patients with mild AD in comparison with a 2-week course of PAS control condition (PAS-C, described below) (rPAS-C).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's disease-rPAS | Experimental | Procedure: Paired Associative StimulationThe intervention procedure will done in this group is r-Paired Associative Stimulation. This involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC |
| Alzheimer's disease-rPAS-C | Placebo comparator | Procedure: Paired Associative Stimulation-ControlThe intervention procedure being done with this group is PAS-C. This is a control Paired Associative Stimulation paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP. |
| Control | Other | Procedure: Paired Associative Stimulation-ControlControls will have a one time Paired Associative Stimulation-Control (PAS-C) paradigm intervention in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (10 listed)
- Age 65 or above
- Meet NINCDS-ADRDA and DSM-IV TR criteria for a current diagnosis of Alzheimer's Disease
- Stable does of acetylcholinesterase inhibitors for at least 3 months
- Willingness and ability to speak English
- Willingness and ability to provide informed consent
Key exclusion criteria (12 listed)
- Meets criteria for an Axis I diagnosis within the past 12 months other than Dementia of the Alzheimer type.
- Mini Mental Status Examination score of 16 or less as described above
- Meets diagnostic criteria for current alcohol or other drug dependence within 6 months of testing
- Electroconvulsive Therapy (ECT) within 6 months of testing.
- Left handedness.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paired Associative StimulationPAS simulates in humans the induction of long-term potentiation (LTP), a prototype of synaptic neuroplasticity. PAS involves the repetitive pairing of electrical stimulation of the median nerve with - 25 ms later - transcranial magnetic stimulation (TMS) of the contralateral DLPFC. As such, these two stimulations arrive simultaneously in the DLPFC and result in potentiation of TMS induced cortical evoked potential, analogous to in vitro LTP. | Procedure or surgery | Alzheimer's disease-rPAS |
| Paired Associative Stimulation-ControlPAS-C is a control PAS paradigm in which TMS to the left DLPFC follows the electrical stimulation of the right median nerve by 100 ms, and, thus, does not result in contemporaneous occurrence of the two stimulations in the cortex and consequently no LTP. | Procedure or surgery | Alzheimer's disease-rPAS-C, Control |
Primary outcome
Paired Associated Stimulation induced Long-term potentiation as a measure of neuroplasticity in the dorsolateral prefrontal cortex
Time frame: 14 days
We are using a novel technique of TMS- EEG as developed by our group. Through this technique, not only motor evoked potential (MEP) but also cortical evoked activity (CEA) is recorded continuously while TMS is being delivered to the cortex. Thus, PAS-induced LTP could be indexed through the potentiation of not only MEP but also of CEA. TMS-EEG has been used by our group and others. Our group has used TMS-EEG in healthy individuals and patients with severe mental illness to study several neurophysiological phenomena in M1 and DLPFC such as cortical inhibition, gamma oscillations, and recently LTP. In summary, we propose to combine PAS with TMS-EEG to assess DLPFC neuroplasticity in patients with mild AD and then deliver a 2-week course of daily repetitive PAS (rPAS) to enhance DLPFC neuroplasticity and function as indexed by the N-back task. This will be measured to see if there are any changes after 1 day, 7 days and 14 days of the intervention procedure.
1 secondary outcome
N-back Task
Time frame: pre-intervention (baseline) and then 1, 7, 14 days after intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2018.
- Derived from this study: PubMed 33190659Kumar S, Zomorrodi R, Ghazala Z, Goodman MS, Blumberger DM, Daskalakis ZJ, Fischer CE, Mulsant BH, Pollock BG, Rajji TK. Effects of repetitive paired associative stimulation on brain plasticity and working memory in Alzheimer's disease: a pilot randomized double-blind-controlled trial. Int Psychogeriatr. 2023 Mar;35(3):143-155. doi: 10.1017/S1041610220003518. Epub 2020 Nov 16.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tarek Rajji, MD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Paired Associative Stimulation in people with Alzheimer's Disease, run by Centre for Addiction and Mental Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Paired Associated Stimulation induced Long-term potentiation as a measure of neuroplasticity in the dorsolateral prefrontal cortex (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01847586, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jan 2018.