Alzheimer's DiseasePhase 2NCT00814697
Effect of Repetitive Transcranial Magnetic Stimulation on Language in Alzheimer's Disease
A Phase 2 study testing Repetitive Transcranial Magnetic Coil Stimulation (rTMS) in people with Alzheimer's Disease and Aphasia, run by The New York Memory Services at 1 site in United States.
Trial summary
The investigators wish to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in patients with Alzheimer's disease (AD). In rTMS, magnetic pulses are used to noninvasively stimulate focal areas of cortex of about a square centimeter in area. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer's Disease, Aphasia, Dementia
- What is being tested?
- Repetitive Transcranial Magnetic Coil Stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have a diagnosis of probable or possible Alzheimer's disease, diagnosed using standardized criteria.
- If subjects are determined by the PI to lack decisional capacity to consent to the study, a legally authorized representative must be available to sign the informed consent on behalf of the subject. In this case the assent of each subject will be obtained as well. If at any time the subject withdraws his or her assent, the subject will be disenrolled from the study.
- Subjects will score at or below 30 on the 60 item naming section of the Boston Diagnostic Aphasia and/or below 50% on the Controlled Word Association (CFL) Category Naming.
Who cannot join
- Subjects newly diagnosed with AD and not yet receiving usual care are not eligible.
- Subjects must not have pacemakers.
- They must not have a history of implanted metal objects.
- They must not have a history of seizures or epilepsy.
- There must not be any recent history of migraines.
- There must not be any history of uncontrolled depression.
- They must not be on any medications that will significantly lower the seizure threshold.
- Any other medical condition that is judged by the PI to make rTMS unsafe for the subject.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label, Exploratory Study of the Efficacy of Repetitive Transcranial Magnetic Stimulation on Naming and Verbal Fluency in Patients With Alzheimer's Disease With Functional Imaging Correlates
The investigators wish to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in patients with Alzheimer's disease (AD). In rTMS, magnetic pulses are used to noninvasively stimulate focal areas of cortex of about a square centimeter in area. rTMS has been approved in the United States for the diagnosis of peripheral nerve conditions.
Depending on the frequency of stimulation, rTMS can preferentially stimulate or inhibit cortical areas. In stroke rehabilitation, for example, inhibition of the contralateral, uninvolved hemisphere by low frequency rTMS has improved movement of the affected limbs because of less aberrant inhibition of the affected hemisphere by the healthy hemisphere. The effects of rTMS has also been investigated and found to be useful in treating refractory depression and depression in Parkinson's disease. In addition, rTMS has improved naming in patients with Alzheimer's disease and has improved cognitive abilities and memory in non-demented older adults. Two studies found that rTMS improved aphasia in patients with stroke. While these studies are small, a review of the literature suggests that there may be a beneficial role for rTMS in patients with chronic neurological conditions. In addition, rTMS appears to be well tolerated, with transient headaches being the most common side effect.
In this small open label study, the investigators wish to investigate the usefulness of bilateral stimulation of the brain region termed the dorsolateral prefrontal cortex (DLPFC) in patients with AD who have naming and language deficits.
Read the detailed description
Subjects for this study will be recruited from Dr. Devi's clinical practice. Eligible subjects must have a diagnosis of possible or probable Alzheimer's disease using NINCDS-ADRDA criteria. The patient and his or her legally authorized representative need to be available to sign the informed consent. The assent of the incapable subject will be obtained prior to enrolling the subject in the study.
Once informed consent and assent are obtained, the subject will have a functional magnetic resonance imaging (fMRI) scan of their brain anytime during the 2 weeks prior to the first study visit. At Visit 1, subjects will undergo a baseline battery of cognitive tests lasting approximately 30 minutes. Subsequently, the subject will undergo rTMS.
During the visit, Dr. Devi will locate the area of the brain to be stimulated and mark that area of the scalp with an indelible skin marker that will wash out over time. In addition, the subjects will be provided with ear plugs to use during stimulation. This process of locating the area to be stimulated will take about an hour and will occur once. Then rTMS will be started and this procedure will take approximately 20-30 minutes (please see the full protocol for a complete description of this process).
Each rTMS stimulation session will last for about 30 minutes, 2 consecutive days a week for 2 weeks. Both immediately prior to the onset of the first rTMS session, and just after the end of the fourth and final rTMS session, subjects will be tested on their cognitive and language skills. These two testing sessions will last 30 minutes each. Subjects will have another fMRI scan anytime during the 2 days after the fourth and final rTMS stimulation session.
Subjects will continue to receive usual care throughout the study period. Any changes to usual treatment will be noted in the study file.
All subjects will be seen again 4 weeks after the final study treatment session and will once again undergo the brief cognitive battery and fMRI scan.
The investigators expect to recruit two subjects at a time for the study and each subject will be enrolled for 5 weeks from the baseline visit.
- Conditions
- Alzheimer's Disease, Aphasia, Dementia
- Being tested
- Repetitive Transcranial Magnetic Coil Stimulation (rTMS)
- Keywords
- Alzheimer, Language, Treatment, TMS, rTMS
- Medical subject headings
- Alzheimer Disease, Aphasia, Dementia, Language
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic Coil Stimulation (rTMS)Device
The first six patients were administered rTMS at 10Hz in 20 trains of 5 seconds with 20 second intervals between trains in each hemisphere. The total number of pulses for each session was set at 1000 pulses. The second six enrolled patients were administered rTMS at 15 Hz in 20 trains of 5 seconds with 25 second intervals between trains in each hemisphere.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Magnetic Stimulation | Experimental | Repetitive Transcranial Magnetic Coil Stimulation (rTMS) treatment in Alzheimer's disease. The Magstim Rapid2 stimulator with a peak magnetic field of 0.5-3.5 Tesla at 100% output was used over the right and left dorsolateral prefrontal cortex. Patients received 4 sessions of rTMS over 2 weeks, lasting approximately 30 minutes, 2 consecutive days a week for 2 weeks. Receives: Device: Repetitive Transcranial Magnetic Coil Stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Assessment Task Scores Before, During and After rTMS.
Cognitive assessment tasks - Boston Diagnostic Aphasia Examination (BDAE), CFL Category naming (CFL), Mini-Mental State Examination (MMSE) - were administered and scored according to standard procedures before, during and 4 weeks after rTMS.
Higher scores are associated with better cognition; No absolute cut-offs were used here as the outcomes were not categorically assessed.
Total possible score ranges by test, lowest to highest:
BDAE - 0 to 15 CFL - 0 to 62 MMSE - 0 to 30 Full range data and means presented below represents range of scores at 4-weeks post-rTMS treatments.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2008 (estimated)
- Study startDec 2008
- Primary completionDec 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- The New York Memory Services
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gayatri Devi, MD, The New York Memory Services
- Investigators
- Gayatri Devi, MD, Principal investigator, The New York Memory Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00814697
- Sponsor's protocol ID
- 91913-5
- Status last verified
- Jan 2014
- First submitted
- 24 Dec 2008
- Last updated
- 28 Jan 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cotelli M, Manenti R, Cappa SF, Geroldi C, Zanetti O, Rossini PM, Miniussi C. Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease. Arch Neurol. 2006 Nov;63(11):1602-4. doi: 10.1001/archneur.63.11.1602.
PubMed 17101829Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.
PubMed 21671144Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM. Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study. J Neural Transm (Vienna). 2011 Mar;118(3):463-71. doi: 10.1007/s00702-010-0578-1. Epub 2011 Jan 19.
PubMed 21246222Rabey JM, Dobronevsky E, Aichenbaum S, Gonen O, Marton RG, Khaigrekht M. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: a randomized, double-blind study. J Neural Transm (Vienna). 2013 May;120(5):813-9. doi: 10.1007/s00702-012-0902-z. Epub 2012 Oct 18.
PubMed 23076723Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C. Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol. 2008 Dec;15(12):1286-92. doi: 10.1111/j.1468-1331.2008.02202.x.
PubMed 19049544Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C. Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7. doi: 10.1136/jnnp.2009.197848. Epub 2010 Jun 23.
PubMed 20574108
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Exploratory Study of the Efficacy of Repetitive Transcranial Magnetic Stimulation on Naming and Verbal Fluency in Patients With Alzheimer's Disease With Functional Imaging Correlates
- ClinicalTrials.gov ID
- NCT00814697
- Acronym / sponsor ID
- 91913-5
- Conditions
- Alzheimer's Disease, Aphasia, Dementia
- Keywords
- Alzheimer, Language, Treatment, TMS, rTMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- The New York Memory ServicesUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 25 Dec 2008 (estimated)
- Results
- Posted 28 Jan 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators wish to investigate the efficacy of targeted repetitive transcranial magnetic stimulation (rTMS) on expressive language in patients with Alzheimer's disease (AD). In rTMS, magnetic pulses are used to noninvasively stimulate focal areas of cortex of about a square centimeter in area. rTMS has been approved in the United States for the diagnosis of peripheral nerve conditions.
Depending on the frequency of stimulation, rTMS can preferentially stimulate or inhibit cortical areas. In stroke rehabilitation, for example, inhibition of the contralateral, uninvolved hemisphere by low frequency rTMS has improved movement of the affected limbs because of less aberrant inhibition of the affected hemisphere by the healthy hemisphere. The effects of rTMS has also been investigated and found to be useful in treating refractory depression and depression in Parkinson's disease. In addition, rTMS has improved naming in patients with Alzheimer's disease and has improved cognitive abilities and memory in non-demented older adults. Two studies found that rTMS improved aphasia in patients with stroke. While these studies are small, a review of the literature suggests that there may be a beneficial role for rTMS in patients with chronic neurological conditions. In addition, rTMS appears to be well tolerated, with transient headaches being the most common side effect.
In this small open label study, the investigators wish to investigate the usefulness of bilateral stimulation of the brain region termed the dorsolateral prefrontal cortex (DLPFC) in patients with AD who have naming and language deficits.
Detailed description
Subjects for this study will be recruited from Dr. Devi's clinical practice. Eligible subjects must have a diagnosis of possible or probable Alzheimer's disease using NINCDS-ADRDA criteria. The patient and his or her legally authorized representative need to be available to sign the informed consent. The assent of the incapable subject will be obtained prior to enrolling the subject in the study.
Once informed consent and assent are obtained, the subject will have a functional magnetic resonance imaging (fMRI) scan of their brain anytime during the 2 weeks prior to the first study visit. At Visit 1, subjects will undergo a baseline battery of cognitive tests lasting approximately 30 minutes. Subsequently, the subject will undergo rTMS.
During the visit, Dr. Devi will locate the area of the brain to be stimulated and mark that area of the scalp with an indelible skin marker that will wash out over time. In addition, the subjects will be provided with ear plugs to use during stimulation. This process of locating the area to be stimulated will take about an hour and will occur once. Then rTMS will be started and this procedure will take approximately 20-30 minutes (please see the full protocol for a complete description of this process).
Each rTMS stimulation session will last for about 30 minutes, 2 consecutive days a week for 2 weeks. Both immediately prior to the onset of the first rTMS session, and just after the end of the fourth and final rTMS session, subjects will be tested on their cognitive and language skills. These two testing sessions will last 30 minutes each. Subjects will have another fMRI scan anytime during the 2 days after the fourth and final rTMS stimulation session.
Subjects will continue to receive usual care throughout the study period. Any changes to usual treatment will be noted in the study file.
All subjects will be seen again 4 weeks after the final study treatment session and will once again undergo the brief cognitive battery and fMRI scan.
The investigators expect to recruit two subjects at a time for the study and each subject will be enrolled for 5 weeks from the baseline visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transcranial Magnetic Stimulation | Experimental | Device: Repetitive Transcranial Magnetic Coil Stimulation (rTMS)Repetitive Transcranial Magnetic Coil Stimulation (rTMS) treatment in Alzheimer's disease. The Magstim Rapid2 stimulator with a peak magnetic field of 0.5-3.5 Tesla at 100% output was used over the right and left dorsolateral prefrontal cortex. Patients received 4 sessions of rTMS over 2 weeks, lasting approximately 30 minutes, 2 consecutive days a week for 2 weeks. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects must have a diagnosis of probable or possible Alzheimer's disease, diagnosed using standardized criteria.
- If subjects are determined by the PI to lack decisional capacity to consent to the study, a legally authorized representative must be available to sign the informed consent on behalf of the subject. In this case the assent of each subject will be obtained as well. If at any time the subject withdraws his or her assent, the subject will be disenrolled from the study.
- Subjects will score at or below 30 on the 60 item naming section of the Boston Diagnostic Aphasia and/or below 50% on the Controlled Word Association (CFL) Category Naming.
Key exclusion criteria (8 listed)
- Subjects newly diagnosed with AD and not yet receiving usual care are not eligible.
- Subjects must not have pacemakers.
- They must not have a history of implanted metal objects.
- They must not have a history of seizures or epilepsy.
- There must not be any recent history of migraines.
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 |
|---|---|---|
| Repetitive Transcranial Magnetic Coil Stimulation (rTMS)The first six patients were administered rTMS at 10Hz in 20 trains of 5 seconds with 20 second intervals between trains in each hemisphere. The total number of pulses for each session was set at 1000 pulses. The second six enrolled patients were administered rTMS at 15 Hz in 20 trains of 5 seconds with 25 second intervals between trains in each hemisphere. | Device | Transcranial Magnetic Stimulation |
Primary outcome
Cognitive Assessment Task Scores Before, During and After rTMS.
Time frame: 6 weeks
Cognitive assessment tasks - Boston Diagnostic Aphasia Examination (BDAE), CFL Category naming (CFL), Mini-Mental State Examination (MMSE) - were administered and scored according to standard procedures before, during and 4 weeks after rTMS. Higher scores are associated with better cognition; No absolute cut-offs were used here as the outcomes were not categorically assessed. Total possible score ranges by test, lowest to highest: BDAE - 0 to 15 CFL - 0 to 62 MMSE - 0 to 30 Full range data and means presented below represents range of scores at 4-weeks post-rTMS treatments.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 17101829Cotelli M, Manenti R, Cappa SF, Geroldi C, Zanetti O, Rossini PM, Miniussi C. Effect of transcranial magnetic stimulation on action naming in patients with Alzheimer disease. Arch Neurol. 2006 Nov;63(11):1602-4. doi: 10.1001/archneur.63.11.1602.
- Background: PubMed 21671144Ahmed MA, Darwish ES, Khedr EM, El Serogy YM, Ali AM. Effects of low versus high frequencies of repetitive transcranial magnetic stimulation on cognitive function and cortical excitability in Alzheimer's dementia. J Neurol. 2012 Jan;259(1):83-92. doi: 10.1007/s00415-011-6128-4. Epub 2011 Jun 14.
- Background: PubMed 21246222Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG, Rabey JM. Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: a proof of concept study. J Neural Transm (Vienna). 2011 Mar;118(3):463-71. doi: 10.1007/s00702-010-0578-1. Epub 2011 Jan 19.
- Background: PubMed 23076723Rabey JM, Dobronevsky E, Aichenbaum S, Gonen O, Marton RG, Khaigrekht M. Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer's disease: a randomized, double-blind study. J Neural Transm (Vienna). 2013 May;120(5):813-9. doi: 10.1007/s00702-012-0902-z. Epub 2012 Oct 18.
- Background: PubMed 19049544Cotelli M, Manenti R, Cappa SF, Zanetti O, Miniussi C. Transcranial magnetic stimulation improves naming in Alzheimer disease patients at different stages of cognitive decline. Eur J Neurol. 2008 Dec;15(12):1286-92. doi: 10.1111/j.1468-1331.2008.02202.x.
- Background: PubMed 20574108Cotelli M, Calabria M, Manenti R, Rosini S, Zanetti O, Cappa SF, Miniussi C. Improved language performance in Alzheimer disease following brain stimulation. J Neurol Neurosurg Psychiatry. 2011 Jul;82(7):794-7. doi: 10.1136/jnnp.2009.197848. Epub 2010 Jun 23.
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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.
Gayatri Devi, MD principal investigator
The New York Memory Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Repetitive Transcranial Magnetic Coil Stimulation (rTMS) in people with Alzheimer's Disease and Aphasia, run by The New York Memory Services at 1 site in United States.
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 3 inclusion and 8 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 28 Jan 2014. 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 United States. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jan 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Cognitive Assessment Task Scores Before, During and After rTMS. (time frame: 6 weeks). 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 NCT00814697, which also lists 6 linked publications.
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 28 Jan 2014.