Brain Injuries, TraumaticNCT03727737
Efficacy of Repetitive Transcranial Magnetic Stimulation for Improvement of Memory in Older Adults With TBI
A study testing Repetitive Transcranial magnetic Stimulation in people with Brain Injuries, Traumatic and Repetitive Transcranial Magnetic Stimulation, run by Palo Alto Veterans Institute for Research at 1 site in United States.
Trial summary
The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive… Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Brain Injuries, Traumatic, Repetitive Transcranial Magnetic Stimulation, Memory Deficits
- What is being tested?
- Repetitive Transcranial magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Oct 2018to 14 Sep 2022
- 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 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 50-75 years, with a high school education
- History of mild or moderate TBI as defined by the DoD/VA Clinical Practice Guidelines for Definition of TBI
- Ability to obtain a Motor Threshold (MT) will be determined during the screening process
- Must be in the chronic stable phase of recovery (>6 months post injury) with residual cognitive difficulties that are affecting daily functioning (including self-reported memory or cognition problems)
- If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and patient will be willing to remain on a stable regimen during the acute treatment phase
- Has an adequately stable condition and environment to enable attendance at scheduled clinic visits
Show all 9Show fewer
- For female participants of child bearing potential, agrees to use one of the following acceptable methods of birth control: abstinence, oral contraceptive, Norplant, Depo-Provera, a condom with spermicide, a cervical cap with spermicide, a diaphragm with spermicide, an intrauterine device, surgical sterilization (having your tubes tied)
- Able to read, verbalize understanding, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments
- Individuals who meet the study criteria but have impaired decision making capacity may participate provided they are able to voluntarily sign an Assent Form and have an LAR who can sign a Consent Form and accompany the participant to all study visits
Who cannot join
- Diagnosed with Dementia
- Pregnant or lactating female.
- Unable to be safely withdrawn, at least two-weeks prior to beginning treatment, from medications that substantially increase the risk of seizures
- Have a cardiac pacemaker or a cochlear implant
- Have an implanted device (deep brain stimulation) or metal in the brain (see standard MRI exclusion criteria including metal screening section in telephone screen, Appendix A)
- Have a mass lesion, cerebral infarct or other active CNS disease, including a seizure disorder
Show all 16Show fewer
- Known current psychosis as determined by DSM-IV coding in chart (Axis I, psychotic disorder, schizophrenia) or a history of a non-mood psychotic disorder
- Diagnosis of Bipolar Affective Disorder I (as determined by chart review and intake interview), since this in conjunction with TBI increases seizure risk
- Current amnesic disorders, dementia, MOCA ≤ 16, or delirium.
- Current substance abuse (not including caffeine or nicotine) as determined by positive toxicology screen, or by history via AUDIT, within 3 months prior to screening
- Prior history of seizures
- Severe TBI or open head injury
- TBI within last 6 months
- Participation in another concurrent clinical trial
- Patients with prior exposure to rTMS (NOTE: TMS is allowed) or ECT
- Active current suicidal intent or plan. Patients at risk for suicide will be required to establish a written safety plan involving their primary psychiatrist. All patients at risk for suicide will be excluded from the study (as per FDA recommendation).
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Palo Alto Health Care System
Palo Alto, California, 94304
About this study
The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.
Read the detailed description
Recent advances in both AD and TBI test non-pharmaceutical interventions that target chronic symptom improvement (e.g., non- invasive brain stimulation, exercise and cognitive training). In order to provide targeted therapies to patients who suffer from chronic sequela of TBI it is necessary to understand mechanisms of repair within the context of an aging brain. Repetitive TMS (rTMS) delivers therapeutic, noninvasive brain stimulation, is FDA-approved for treatment for major depression and currently used for treatment of pain, PTSD, anxiety, improvement of executive function in mild and moderate TBI, severe TBI, memory enhancement and dementia.
This treatment can induce neuronal long-term potentiation resulting in synaptic repair leading to improvements in memory function through hippocampal- cortical circuits and brain connectivity measured by resting state-fMRI (rs fMRI) particularly in default mode and central executive network (DMN \& CEN). The study primarily proposes to assess the efficacy of rTMS to improve memory performance and to test rs-fMRI (i.e. DMN) as a potential biomarker to capture response to treatment in older patients suffering with chronic symptoms related to previous brain injuries (depression, PTSD etc). In addition, the study will assess other established biomarkers longitudinally (e.g.,hypometabolism via PET FDG, cortical oscillation via electroencephalography (EEG), Brain Derived Nerve Growth Factor (BDNF)and hippocampal volume from structural MRI) to capture patient response to treatment that may signal early dementia.
HYPOTHESES:
Primary:
Subjects with TBI who receive active rTMS treatment (rTMS_A) will: a) show significantly greater improvement from baseline in memory performance post rTMS intervention compared to subjects who received sham rTMS treatment (rTMS_S), and b) show stronger functional connectivity within and between DMN and CEN post rTMS intervention compared to patients who received sham (rTMS_S).
Secondary:
- Quality of Life (QOL): scores on QOL scale will improve with rTMS treatment in patients who receive rTMS treatment.
- Sustained Improvement: At 6-month follow-up, patients with TBI in rTMS_A group would be more likely to have sustained greater brain connectivity compared to patients in the rTMS_S group predicting better memory performance.
- Moderators of Response: The following variables may moderate memory function improvement in patients with TBI post intervention and at 6-month follow-up: Age, health condition variables (severity of symptoms at baseline, time to injury, baseline cognitive performance, TBI type,comorbidities (PTSD, sleep, depression), substance abuse, medication use, fatigue); physiological and biological variables (baseline hippocampal volume and/or microstructure, baseline connectivity in DMN \& CEN, EEG resting and task-related cortical oscillations, and Brain Derived Neurotrophic Factor (BDNF) genotype.
- Mediators of Response: To assess the mechanism of rTMS in synaptic repair/regeneration, pre and post changes will be assessed in depression and PTSD measures, Plasma BDNF, FDG PET hypometabolism in precuneus/posterior cingulate area, EEG resting and task-related cortical oscillations, and connectivity of DLPFC (stimulation site \& part of CEN) with other DMN.
SPECIFIC OBJECTIVES:
Primary Objective: a) To assess the efficacy of rTMS to predict improvement in memory performance pre and post rTMS intervention in older patients with TBI, and b) To assess rs-fMRI as a biomarker to detect these changes in memory performance.
Secondary Objective: To assess the mechanism of rTMS in synaptic repair/regeneration by assessment of structure \& functional brain activity (PET/MRI, fMRI, \& EEG), genetic, cognitive and behavioral function factors (including QOL, depression and PTSD).
- Conditions
- Brain Injuries, Traumatic, Repetitive Transcranial Magnetic Stimulation, Memory Deficits, Aging
- Being tested
- Repetitive Transcranial magnetic Stimulation
- Keywords
- repetitive Transcranial Magnetic Stimulation, Brain Injuries, Traumatic
- Medical subject headings
- Brain Injuries, Traumatic, Memory Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial magnetic StimulationDevice
Also called rTMS
RTMS will be delivered via magventure machine, on an approved FDA IDE protocol to DLPFC region to improve memory in older adults (veterans and non-veterans) with mild and moderate TBI.
| Study group | Role | What they receive |
|---|---|---|
| Sham | No intervention | Patients with mild and moderate TBI will be assigned randomly to this arm and will not receive treatment |
| ACTIVE | Active comparator | Patients with mild and moderate TBI will be assigned randomly to this arm and will receive treatment Receives: Device: Repetitive Transcranial magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
CANTAB Paired Associates Learning (PAL)
Test for visual memory and new learning: it is a hippocampal-mediated paired associates learning task. This test has twenty-one outcome measures, covering the errors made by the participant, the number of trials required to locate the pattern(s) correctly, memory scores and stages completed (Administration time 10 minutes). The main score provided is the sum of pairs reproduced over three trials (range: 0-30). We will use the average number of trials needed to succeed on PAL task as the main outcome measure.
Measured: 2-4 weeks
Secondary outcomes (1)
Functional Connectivity Changes in the Brain
Neuroimaging using PET/MRI to determine Functional Connectivity in Default Mode Network (DMN) and Central Executive Network (CEN) systems in the brain following rTMS treatment. we will do this by doing ICA analysis for each network focused from the stimulation site.
Measured: 2-4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2018
- Study start23 Oct 2018
- Primary completion14 Sep 2022
- Study completion14 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain Injuries, TraumaticStudies 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
- Model description
- The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Palo Alto Veterans Institute for Research
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University, The Defense and Veterans Brain Injury Center
- Responsible party
- Principal investigator, Maheen M Adamson, Palo Alto Veterans Institute for Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03727737
- Sponsor's protocol ID
- ADA0007AGG
- Status last verified
- Apr 2023
- First submitted
- 23 Oct 2018
- Last updated
- 11 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Repetitive Transcranial Magnetic Stimulation for Improvement of Memory in Older Adults With TBI
- ClinicalTrials.gov ID
- NCT03727737
- Acronym / sponsor ID
- ADA0007AGG
- Conditions
- Brain Injuries, Traumatic, Repetitive Transcranial Magnetic Stimulation, Memory Deficits, Aging
- Keywords
- repetitive Transcranial Magnetic Stimulation, Brain Injuries, Traumatic
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Palo Alto Veterans Institute for ResearchUniversity, hospital or other
- Collaborators
- Stanford University, The Defense and Veterans Brain Injury Center
- Study start
- 23 Oct 2018 (actual)
- Primary completion
- 14 Sep 2022 (actual)
- Study completion
- 14 Sep 2022 (actual)
- First posted
- 1 Nov 2018 (actual)
- 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 proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.
Detailed description
Recent advances in both AD and TBI test non-pharmaceutical interventions that target chronic symptom improvement (e.g., non- invasive brain stimulation, exercise and cognitive training). In order to provide targeted therapies to patients who suffer from chronic sequela of TBI it is necessary to understand mechanisms of repair within the context of an aging brain. Repetitive TMS (rTMS) delivers therapeutic, noninvasive brain stimulation, is FDA-approved for treatment for major depression and currently used for treatment of pain, PTSD, anxiety, improvement of executive function in mild and moderate TBI, severe TBI, memory enhancement and dementia.
This treatment can induce neuronal long-term potentiation resulting in synaptic repair leading to improvements in memory function through hippocampal- cortical circuits and brain connectivity measured by resting state-fMRI (rs fMRI) particularly in default mode and central executive network (DMN \& CEN). The study primarily proposes to assess the efficacy of rTMS to improve memory performance and to test rs-fMRI (i.e. DMN) as a potential biomarker to capture response to treatment in older patients suffering with chronic symptoms related to previous brain injuries (depression, PTSD etc). In addition, the study will assess other established biomarkers longitudinally (e.g.,hypometabolism via PET FDG, cortical oscillation via electroencephalography (EEG), Brain Derived Nerve Growth Factor (BDNF)and hippocampal volume from structural MRI) to capture patient response to treatment that may signal early dementia.
HYPOTHESES:
Primary:
Subjects with TBI who receive active rTMS treatment (rTMS_A) will: a) show significantly greater improvement from baseline in memory performance post rTMS intervention compared to subjects who received sham rTMS treatment (rTMS_S), and b) show stronger functional connectivity within and between DMN and CEN post rTMS intervention compared to patients who received sham (rTMS_S).
Secondary:
- Quality of Life (QOL): scores on QOL scale will improve with rTMS treatment in patients who receive rTMS treatment.
- Sustained Improvement: At 6-month follow-up, patients with TBI in rTMS_A group would be more likely to have sustained greater brain connectivity compared to patients in the rTMS_S group predicting better memory performance.
- Moderators of Response: The following variables may moderate memory function improvement in patients with TBI post intervention and at 6-month follow-up: Age, health condition variables (severity of symptoms at baseline, time to injury, baseline cognitive performance, TBI type,comorbidities (PTSD, sleep, depression), substance abuse, medication use, fatigue); physiological and biological variables (baseline hippocampal volume and/or microstructure, baseline connectivity in DMN \& CEN, EEG resting and task-related cortical oscillations, and Brain Derived Neurotrophic Factor (BDNF) genotype.
- Mediators of Response: To assess the mechanism of rTMS in synaptic repair/regeneration, pre and post changes will be assessed in depression and PTSD measures, Plasma BDNF, FDG PET hypometabolism in precuneus/posterior cingulate area, EEG resting and task-related cortical oscillations, and connectivity of DLPFC (stimulation site \& part of CEN) with other DMN.
SPECIFIC OBJECTIVES:
Primary Objective: a) To assess the efficacy of rTMS to predict improvement in memory performance pre and post rTMS intervention in older patients with TBI, and b) To assess rs-fMRI as a biomarker to detect these changes in memory performance.
Secondary Objective: To assess the mechanism of rTMS in synaptic repair/regeneration by assessment of structure \& functional brain activity (PET/MRI, fMRI, \& EEG), genetic, cognitive and behavioral function factors (including QOL, depression and PTSD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The proposed study will evaluate the safety, durability and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a promising non-invasive therapeutic treatment for improving memory in older adults with mild or moderate Traumatic Brain Injury (TBI) who have been experiencing residual memory or cognitive problems that affect daily functioning.
| Arm | Type | Receives |
|---|---|---|
| Sham | No intervention | –Patients with mild and moderate TBI will be assigned randomly to this arm and will not receive treatment |
| ACTIVE | Active comparator | Device: Repetitive Transcranial magnetic StimulationPatients with mild and moderate TBI will be assigned randomly to this arm and will receive treatment |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age 50-75 years, with a high school education
- History of mild or moderate TBI as defined by the DoD/VA Clinical Practice Guidelines for Definition of TBI
- Ability to obtain a Motor Threshold (MT) will be determined during the screening process
- Must be in the chronic stable phase of recovery (>6 months post injury) with residual cognitive difficulties that are affecting daily functioning (including self-reported memory or cognition problems)
- If on a psychotropic medication regimen, that regimen will be stable for at least 4 weeks prior to entry to the study and patient will be willing to remain on a stable regimen during the acute treatment phase
Key exclusion criteria (16 listed)
- Diagnosed with Dementia
- Pregnant or lactating female.
- Unable to be safely withdrawn, at least two-weeks prior to beginning treatment, from medications that substantially increase the risk of seizures
- Have a cardiac pacemaker or a cochlear implant
- Have an implanted device (deep brain stimulation) or metal in the brain (see standard MRI exclusion criteria including metal screening section in telephone screen, Appendix A)
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 StimulationAlso: rTMSRTMS will be delivered via magventure machine, on an approved FDA IDE protocol to DLPFC region to improve memory in older adults (veterans and non-veterans) with mild and moderate TBI. | Device | ACTIVE |
Primary outcome
CANTAB Paired Associates Learning (PAL)
Time frame: 2-4 weeks
Test for visual memory and new learning: it is a hippocampal-mediated paired associates learning task. This test has twenty-one outcome measures, covering the errors made by the participant, the number of trials required to locate the pattern(s) correctly, memory scores and stages completed (Administration time 10 minutes). The main score provided is the sum of pairs reproduced over three trials (range: 0-30). We will use the average number of trials needed to succeed on PAL task as the main outcome measure.
1 secondary outcome
Functional Connectivity Changes in the Brain
Time frame: 2-4 weeks
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 11 Apr 2023.
Related trials for Brain Injuries, Traumatic
Active, not recruitingObservational study
Transforming Research and Clinical Knowledge in Traumatic Brain Injury Epileptogenesis Project (TRACK-TBI EPI)
Traumatic Brain Injury, Post-traumatic Epilepsy
Enrolling by invitationPhase 1
Pilot Safety and Exploratory Efficacy of PSC-05 for the Treatment of Chronic Mild Traumatic Brain Injury
Mild Traumatic Brain Injury
RecruitingObservational study
Intracranial Pressure Monitoring in Moderate Traumatic Brain Injury
Moderate Traumatic Brain Injury
Not yet recruitingPhase 1
Nanopulse Laser Therapy
TBI (Traumatic Brain Injury)
RecruitingObservational study
Effect of Different Intravenous Fluids on Post-operative Chronic Subdural Hematoma Size and Recurrence
Chronic Subdural Hematoma
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial magnetic Stimulation in people with Brain Injuries, Traumatic and Repetitive Transcranial Magnetic Stimulation, run by Palo Alto Veterans Institute for Research 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 9 inclusion and 16 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 11 Apr 2023. 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?
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?
CANTAB Paired Associates Learning (PAL) (time frame: 2-4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Apr 2023.