AgingWMTMSNCT02767323
Using TMS to Increase Executive Function in Older Adults
A study testing rTMS in people with Aging, run by Duke University at 1 site in United States.
Trial summary
Cognitive decline and dementia have become important public health issues in our time as medical science has increased lifespan and our society becomes progressively older. A great deal of the cognitive decline due to aging can be explained by decline in working memory (WM), a mental function central to cognition in… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- rTMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 184 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2016to 16 Mar 2020
- Phase
- Interventional
- 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 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age Restrictions: Young Group (from 18 to 35 years old), Elderly Group (from 60 to 80 years old).
- Use of effective method of birth control for women of childbearing capacity.
- Willing to provide informed consent.
Who cannot join
- Current or recent (within the past 6 months) history of substance abuse or dependence.
- Current serious medical illness.
- History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
- Inability or unwilling to give informed consent.
- Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
- For subjects age > 59 years, a total scaled score < 8 on the Dementia Rating Scale-2.
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- Clinically defined neurological disorder.
- Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure, or currently taking medication that lowers the seizure threshold.
- Claustrophobia (MRI scanner).
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: Using fMRI-guided TMS to Increase Central Executive Function in Older Adults
Cognitive decline and dementia have become important public health issues in our time as medical science has increased lifespan and our society becomes progressively older. A great deal of the cognitive decline due to aging can be explained by decline in working memory (WM), a mental function central to cognition in which aging deficits appear almost universally. Attempts to use WM training to increase WM ability in older adults has had some success, but the transfer of performance enhancements caused by this training to other cognitive skills is controversial. Another intervention that shows much promise is noninvasive stimulation of cerebral cortex using transcranial magnetic stimulation (TMS), which has been shown to increase performance in many cognitive tasks.
Here, the investigator proposes to use fMRI-guided rTMS to enhance working memory performance. This will be achieved through three Aims. In the first, registered on this record, the investigator will stimulate both old and young healthy adults while they perform the WM task that will engage the frontoparietal network. To define the optimal rTMS target, rTMS will be applied over the dorsolateral prefrontal cortex (DLPFC: Aim 1a); or over the parietal cortex (PC: Aim 1b). These regions are involved not only in the maintenance of items in WM, but also in their manipulation, therefore applying rTMS over these areas should create WM performance enhancements that will be long-lasting. In Aim 1c, a direct within-subject comparison of these 2 targeted sites is performed.
In the second and third Aims, older adults will receive active or sham rTMS over the optimal target (defined in Arm 1) during two weeks of daily sessions while they perform the WM tasks. In the second Aim, the investigator hopes to demonstrate that the cumulative effect of multiple TMS sessions, in tandem with the synergistic effects of simultaneous TMS + WM training, create WM performance enhancements greater than those found with WM training alone, whose effects are long-lasting, continuing a month following the course of TMS sessions. In the third, the investigator will investigate whether the WM enhancements generated by the two weeks of TMS sessions will generalize to other cognitive tasks. The success of these 3 Aims will provide proof in principle for long-lasting, transferable effects of TMS in remediating WM and more general cognitive deficits due to aging, and point to a possible non-invasive brain stimulation therapy for cognitive decline in healthy aging and in dementia. This record is a reflection of Aim1, Aim 2 and 3 will be registered separately.
- Conditions
- Aging
- Being tested
- rTMS, Sham rTMS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rTMSDevice
excitatory 5Hz rTMS will be used
Sham rTMSDevice
an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used
| Study group | Role | What they receive |
|---|---|---|
| Active or Sham rTMS over the DLPFC (Aim1a) | Experimental | excitatory rTMS applied over the DLPFC (fMRI-guided). Active and Sham rTMS will be tested in a within subject design Receives: Device: rTMS; Device: Sham rTMS |
| Active or Sham rTMS over the Parietal cortex (Aim1b) | Experimental | excitatory rTMS applied over the parietal cortex (fMRI-guided). Active and Sham rTMS will be tested in a within subject design Receives: Device: rTMS; Device: Sham rTMS |
| Active or Sham rTMS over the DLPFC and the Parietal cortex (Aim1c) | Experimental | excitatory rTMS applied over the DLPFC and the parietal cortex (fMRI-guided). Active and Sham rTMS will be tested in a within subject design Receives: Device: rTMS; Device: Sham rTMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage)
Accuracy (in percentage) will be assessed to evaluate the acute effect of rTMS. The accuracy provided below are the ones obtained in the hardest condition of the working memory task.
Measured: During the rTMS session, on average 2 hours per visit.
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Reaction Time of Correct Response (in ms)
Reaction Time of correct response (in ms) will be assessed to evaluate the acute effect of rTMS. The reaction times provided below are the ones obtained in the hardest condition of the working memory task.
Measured: During the rTMS session, on average 2 hours per visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2016 (estimated)
- Study start15 Aug 2016
- Primary completion16 Mar 2020
- Study completion16 Mar 2020
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 (1)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 184 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Lawrence Appelbaum, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02767323
- Sponsor's protocol ID
- Pro00065334
- Other IDs
- 1R01AG050618-01
- Acronym
- WMTMS
- Status last verified
- Mar 2021
- First submitted
- 5 May 2016
- Last updated
- 5 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Crowell CA, Davis SW, Beynel L, Deng L, Lakhlani D, Hilbig SA, Palmer H, Brito A, Peterchev AV, Luber B, Lisanby SH, Appelbaum LG, Cabeza R. Older adults benefit from more widespread brain network integration during working memory. Neuroimage. 2020 Sep;218:116959. doi: 10.1016/j.neuroimage.2020.116959. Epub 2020 May 20.
PubMed 32442638
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using fMRI-guided TMS to Increase Central Executive Function in Older Adults
- ClinicalTrials.gov ID
- NCT02767323
- Acronym / sponsor ID
- WMTMS / Pro00065334
- Conditions
- Aging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 184 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- 15 Aug 2016 (actual)
- Primary completion
- 16 Mar 2020 (actual)
- Study completion
- 16 Mar 2020 (actual)
- First posted
- 10 May 2016 (estimated)
- Results
- Posted 5 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cognitive decline and dementia have become important public health issues in our time as medical science has increased lifespan and our society becomes progressively older. A great deal of the cognitive decline due to aging can be explained by decline in working memory (WM), a mental function central to cognition in which aging deficits appear almost universally. Attempts to use WM training to increase WM ability in older adults has had some success, but the transfer of performance enhancements caused by this training to other cognitive skills is controversial. Another intervention that shows much promise is noninvasive stimulation of cerebral cortex using transcranial magnetic stimulation (TMS), which has been shown to increase performance in many cognitive tasks.
Here, the investigator proposes to use fMRI-guided rTMS to enhance working memory performance. This will be achieved through three Aims. In the first, registered on this record, the investigator will stimulate both old and young healthy adults while they perform the WM task that will engage the frontoparietal network. To define the optimal rTMS target, rTMS will be applied over the dorsolateral prefrontal cortex (DLPFC: Aim 1a); or over the parietal cortex (PC: Aim 1b). These regions are involved not only in the maintenance of items in WM, but also in their manipulation, therefore applying rTMS over these areas should create WM performance enhancements that will be long-lasting. In Aim 1c, a direct within-subject comparison of these 2 targeted sites is performed.
In the second and third Aims, older adults will receive active or sham rTMS over the optimal target (defined in Arm 1) during two weeks of daily sessions while they perform the WM tasks. In the second Aim, the investigator hopes to demonstrate that the cumulative effect of multiple TMS sessions, in tandem with the synergistic effects of simultaneous TMS + WM training, create WM performance enhancements greater than those found with WM training alone, whose effects are long-lasting, continuing a month following the course of TMS sessions. In the third, the investigator will investigate whether the WM enhancements generated by the two weeks of TMS sessions will generalize to other cognitive tasks. The success of these 3 Aims will provide proof in principle for long-lasting, transferable effects of TMS in remediating WM and more general cognitive deficits due to aging, and point to a possible non-invasive brain stimulation therapy for cognitive decline in healthy aging and in dementia. This record is a reflection of Aim1, Aim 2 and 3 will be registered separately.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Active or Sham rTMS over the DLPFC (Aim1a) | Experimental | Device: rTMS, Device: Sham rTMSexcitatory rTMS applied over the DLPFC (fMRI-guided). Active and Sham rTMS will be tested in a within subject design |
| Active or Sham rTMS over the Parietal cortex (Aim1b) | Experimental | Device: rTMS, Device: Sham rTMSexcitatory rTMS applied over the parietal cortex (fMRI-guided). Active and Sham rTMS will be tested in a within subject design |
| Active or Sham rTMS over the DLPFC and the Parietal cortex (Aim1c) | Experimental | Device: rTMS, Device: Sham rTMSexcitatory rTMS applied over the DLPFC and the parietal cortex (fMRI-guided). Active and Sham rTMS will be tested in a within subject design |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age Restrictions: Young Group (from 18 to 35 years old), Elderly Group (from 60 to 80 years old).
- Use of effective method of birth control for women of childbearing capacity.
- Willing to provide informed consent.
Key exclusion criteria (10 listed)
- Current or recent (within the past 6 months) history of substance abuse or dependence.
- Current serious medical illness.
- History of seizure, epilepsy, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by rTMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator)
- Inability or unwilling to give informed consent.
- Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV).
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 |
|---|---|---|
| rTMSexcitatory 5Hz rTMS will be used | Device | Active or Sham rTMS over the DLPFC (Aim1a), Active or Sham rTMS over the DLPFC and the Parietal cortex (Aim1c), Active or Sham rTMS over the Parietal cortex (Aim1b) |
| Sham rTMSan electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used | Device | Active or Sham rTMS over the DLPFC (Aim1a), Active or Sham rTMS over the DLPFC and the Parietal cortex (Aim1c), Active or Sham rTMS over the Parietal cortex (Aim1b) |
Primary outcome
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage)
Time frame: During the rTMS session, on average 2 hours per visit.
Accuracy (in percentage) will be assessed to evaluate the acute effect of rTMS. The accuracy provided below are the ones obtained in the hardest condition of the working memory task.
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Reaction Time of Correct Response (in ms)
Time frame: During the rTMS session, on average 2 hours per visit
Reaction Time of correct response (in ms) will be assessed to evaluate the acute effect of rTMS. The reaction times provided below are the ones obtained in the hardest condition of the working memory task.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32442638Crowell CA, Davis SW, Beynel L, Deng L, Lakhlani D, Hilbig SA, Palmer H, Brito A, Peterchev AV, Luber B, Lisanby SH, Appelbaum LG, Cabeza R. Older adults benefit from more widespread brain network integration during working memory. Neuroimage. 2020 Sep;218:116959. doi: 10.1016/j.neuroimage.2020.116959. Epub 2020 May 20.
- Individual participant dataSharing planned: Undecided
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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.
Lawrence Appelbaum principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rTMS in people with Aging, run by Duke University 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 10 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 5 Apr 2021. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2021). 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?
Acute Effect of a rTMS Session on the Performance for a Working Memory Task, as Measured by Accuracy (in Percentage) (time frame: During the rTMS session, on average 2 hours per visit.). The study lists 2 primary outcomes in all. 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 NCT02767323, 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 5 Apr 2021.