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| ID | Type | Description | Link |
|---|---|---|---|
| RF1MH116920 | U.S. NIH Grant/Contract | View source |
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The study was terminated because our funding agency, the NIH, did not grant a no-cost extension to meet our recruitment goals.
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute of Mental Health (NIMH) | NIH |
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This study uses different types of functional magnetic resonance imagining (fMRI) to generate individual transcranial magnetic stimulation (TMS) targets. During the TMS/fMRI imagining sessions, the investigators stimulate a target of either high or low regional controllability during a working memory task to investigate network responses and the impact of TMS on behavior.
This study involves up to 4 visits for patients with Attention Deficit Hyperactivity Disorder (ADHD) and 5 visits for non-symptomatic subjects.
Visit 1 has both remote and in-person procedures. The remote part of visit 1 will consist of a consenting and extended screening visit. The in-person procedures of visit 1 will be scheduled for the same day as visit 2. Before visit 2, the investigators will demonstrate TMS to make sure participants can tolerate the stimulation.
Visit 2 consists of an hour-long baseline MRI Scan along with an assessment session. The baseline MRI scan is used to find individualized TMS targets. The assessment session of visit 2 will be done over a video call. During the video call, the investigators will have the participant complete some computerized tasks and assessments.
Visit 3 will be a 1-hour long TMS/fMRI session, where the participant will complete a working memory task twice while single pulse TMS is being delivered. In between the 2 rounds of the working memory task, the participant will receive 4 minutes of repetitive stimulation.
Non-symptomatic subjects will have a fourth visit that mirrors visit 3.
Visit 5 or Visit 4 for ADHD participants, will take place if behavioral task is available, otherwise study participation will be considered complete. During the optional visit, participants may complete behavioral tasks during an MRI scan. No TMS will be administered during the final visit.
Participants will receive the compensation at the end of their participation. Payment may be given earlier if the participant withdraws from the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High regional controllability TMS target in non-symptomatic participants | Experimental | We will administer TMS to an individualized target of high regional controllability while non-symptomatic participant completes a working memory task inside the MRI scanner. |
|
| Low controllability TMS target in non-symptomatic participants | Active Comparator | We will administer TMS to an individualized target of low regional controllability while non-symptomatic participant completes a working memory task inside the MRI scanner. |
|
| High regional controllability TMS target in ADHD participants | Experimental | We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transcranial Magnetic Stimulation (TMS) | Device | Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of Single TMS Pulses to a High vs. Low Regional Controllability Target on Working Memory Task Performance | Control participants complete two visits in which they undergo functional MRI interleaved with TMS targeting a specific controllability region. Each visit involves administering single pulses of TMS while participants perform a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high regional controllability target and the other stimulating a low regional controllability target. The effect of single-pulse TMS on N-back task performance will be assessed before rTMS administration using percent accuracy scores. Percent accuracy reflects the percentage of correct trials out of the total Nback trials, with higher scores indicating better task performance. | Up to 3 weeks |
| Effect of rTMS on Working Memory Task Performance | Control participants complete two visits with functional MRI interleaved with TMS targeting a specific controllability region. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted controllability region is counterbalanced, with one visit stimulating a high controllability target and the other a low controllability target. The effect of rTMS on N-back task performance will be assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy, indicating the percentage of correct trials, will be analyzed for both high and low regional controllability targets across the visits. | Pre- and post-TMS at visits 3 (approximately day 7) and 4 (approximately day 14) |
| Effect of rTMS to High vs. Low Controllability Target on Working Memory Task Performance | Control participants complete two visits where they undergo functional MRI interleaved with TMS targeting specific brain controllability regions. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high controllability target and the other a low controllability target. In order to compare the effect of rTMS to high versus low controllability targets on working memory performance, we will assess the change in N-back task percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS to both regions. A greater percent change (positive value) means improved task performance following rTMS. |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of rTMS on Working Memory Performance in Participants With ADHD | Participants with ADHD complete a single visit where they undergo functional MRI interleaved with TMS to a high controllability region. During the visit, participants receive single pulses of TMS while performing the working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The effect of rTMS on N-back task performance is assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy reflects the percentage of correct trials out of the total number of N-back trials, with higher percent accuracy indicating better performance. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
Of the 68 participants screened for the study, 45 were enrolled and 23 did not start study procedures (13 screen failed, 4 withdrew from participation, and 6 lost to follow-up)
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| ID | Title | Description |
|---|---|---|
| FG000 | Non-symptomatic Participants High Modal Controllability First, Then Low Modal Controllability Target | Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a high modal controllability target then the alternate low modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high & low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task. |
| FG001 | Non-symptomatic Participants Low Modal Controllability First, Then High Modal Controllability Target | Non-symptomatic participants will complete 2 TMS/fMRI visits, first receiving TMS to a low modal controllability target then the alternate high modal controllability target for the second TMS/fMRI. We will administer TMS to an individualized target of high & low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task. |
| FG002 | High Modal Controllability TMS Target in ADHD Participants | We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner. Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline MRI and Assessments |
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| |||||||||||||||||||||
| TMS/fMRI #1 |
| ||||||||||||||||||||||
| Washout (at Least 7 Days) |
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| TMS/fMRI #2 (Only for Non-symptomatic) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Non-symptomatic Participants | Non-symptomatic participants or those without any psychiatric history complete two visits involving functional MRI (fMRI) and TMS. Each visit targets a specific brain controllability region, with one visit focusing on a high controllability region and the other on a low controllability region. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Effect of Single TMS Pulses to a High vs. Low Regional Controllability Target on Working Memory Task Performance | Control participants complete two visits in which they undergo functional MRI interleaved with TMS targeting a specific controllability region. Each visit involves administering single pulses of TMS while participants perform a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high regional controllability target and the other stimulating a low regional controllability target. The effect of single-pulse TMS on N-back task performance will be assessed before rTMS administration using percent accuracy scores. Percent accuracy reflects the percentage of correct trials out of the total Nback trials, with higher scores indicating better task performance. | Of the 23 participants who completed all study procedures, 2 participants were unusable for this analysis. | Posted | Mean | 95% Confidence Interval | percentage of accuracy | Up to 3 weeks |
|
Adverse event data was collected from study enrollment until study completion (up to 3 weeks).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High & Low Modal Controllability TMS Target in Non-symptomatic Participants | Non-symptomatic participants will complete 2 TMS/fMRI visits with alternate targets for a high and low modal controllability target. We will administer TMS to an individualized target of high & low modal controllability while asymptomatic participant completes a working memory task inside the MRI scanner. Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache, dizziness, and nausea | General disorders | Systematic Assessment | Subject reported headache, dizziness, and nausea during TMS/fMRI. TMS was stopped and subject withdrew from study. |
Enrollment goals were not completed due to delays resulting from COVID and not being granted a second no-cost extension.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Desmond Oathes, Principal Investigator | University of Pennsylvania | 215-573-9390 | oathes@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 23, 2022 | Jul 30, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 15, 2023 | Jul 30, 2024 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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All healthy participants will have TMS administered to both their high and low regional controllability targets, but the order is randomized and counterbalanced.
ADHD participants will have TMS administered to only their high regional controllability target.
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This study will use a single-blind design.
| High controllability TMS target | Procedure | Administer TMS to a brain regions with high regional controllability while the subject engages in a working memory task. |
|
| Up to 3 weeks |
| Pre- and post-TMS at visit 3 (approximately day 7) |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
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| NOT COMPLETED |
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| ADHD Participants |
Participants diagnosed with ADHD or ADD complete one visit involving functional MRI (fMRI) and TMS. This visit focuses exclusively on a high controllability brain region. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| E-SWAN ADHD scale | The Extended Strengths and Weaknesses of Attention-Deficit/Hyperactivity Symptoms and Normal Behavior Scale (E-SWAN) was administered via survey on their baseline MRI to assess ADHD symptoms. This scale includes 18 items rated from -3 (far below average) to 3 (far above average), divided into two subscales: Inattention and Hyperactivity/Impulsivity. Average scores for each subscale are used to interpret results. An average score above 0.745 on a subscale indicates presence of ADHD symptoms, with higher scores reflecting more severe symptoms and negative scores suggesting fewer or no symptoms. | Mean | Standard Deviation | units on a scale |
|
| Title |
|---|
| Description |
|---|
| OG000 | TMS to a High Controllability Target in Non-Symptomatic Participants | Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a high controllability region. |
| OG001 | TMS to a Low Controllability Target in Non-Symptomatic Participants | Non-symptomatic participants undergoing functional MRI (fMRI) interleaved with TMS to a low controllability region. |
|
|
|
| Primary | Effect of rTMS on Working Memory Task Performance | Control participants complete two visits with functional MRI interleaved with TMS targeting a specific controllability region. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted controllability region is counterbalanced, with one visit stimulating a high controllability target and the other a low controllability target. The effect of rTMS on N-back task performance will be assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy, indicating the percentage of correct trials, will be analyzed for both high and low regional controllability targets across the visits. | Of the 23 participants who completed all study procedures, 2 participant's data was unusable for this analysis for the percent change comparison and high controllability group. Only 1 participant was unusable for the low controllability group. | Posted | Mean | 95% Confidence Interval | percentage accuracy | Pre- and post-TMS at visits 3 (approximately day 7) and 4 (approximately day 14) |
|
|
|
|
| Secondary | Effect of rTMS on Working Memory Performance in Participants With ADHD | Participants with ADHD complete a single visit where they undergo functional MRI interleaved with TMS to a high controllability region. During the visit, participants receive single pulses of TMS while performing the working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while completing the N-back task. The effect of rTMS on N-back task performance is assessed by comparing participants' percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS. Percent accuracy reflects the percentage of correct trials out of the total number of N-back trials, with higher percent accuracy indicating better performance. | Of the 13 participants with ADHD that completed the study, 1 participant's data was unusable for this analysis. | Posted | Mean | 95% Confidence Interval | percentage of accuracy | Pre- and post-TMS at visit 3 (approximately day 7) |
|
|
|
|
| Primary | Effect of rTMS to High vs. Low Controllability Target on Working Memory Task Performance | Control participants complete two visits where they undergo functional MRI interleaved with TMS targeting specific brain controllability regions. Each visit includes single pulses of TMS during a working memory task (N-back), followed by a brief round of repetitive TMS (rTMS), and concluding with another set of single pulses while performing the N-back task. The targeted brain region is counterbalanced across visits, with one visit stimulating a high controllability target and the other a low controllability target. In order to compare the effect of rTMS to high versus low controllability targets on working memory performance, we will assess the change in N-back task percent accuracy scores before (pre-rTMS) and after (post-rTMS) rTMS to both regions. A greater percent change (positive value) means improved task performance following rTMS. | Of the 23 participants who completed all study procedures, 2 participant's data was unusable for this analysis for the percent change comparison and high controllability group. Only 1 participant was unusable for the low controllability group. | Posted | Mean | 95% Confidence Interval | percentage accuracy change | Up to 3 weeks |
|
|
|
|
| 0 |
| 26 |
| 0 |
| 26 |
| 0 |
| 26 |
| EG001 | High Modal Controllability TMS Target in ADHD Participants | We will administer TMS to an individualized target of high regional controllability while patient completes a working memory task inside the MRI scanner. Transcranial Magnetic Stimulation (TMS): Transcranial Magnetic Stimulation (TMS) is a non-invasive form of brain stimulation. TMS can influence activity in various brain regions, and it allows researchers to test or modify brain circuit communication. High controllability TMS target: Administer TMS to a brain regions with high modal controllability while the subject engages in a working memory task. | 0 | 19 | 0 | 19 | 2 | 19 |
|
| Minor Discomfort | General disorders | Systematic Assessment | Subject reported weird feeling in ear while receiving rTMS inside the MRI. |
|
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Statistics are from 2-tailed t-test comparing pre-rTMS and post-rTMS 2-back percent accuracy scores for a low controllability TMS target. Alternative hypothesis: true mean is not equal to 0.
| t-test, 2 sided |
df = 20 |
| <0.04 |
| Mean Difference (Final Values) |
| 6.36 |
| 2-Sided |
| Superiority |