Major Depressive DisorderNCT03378570
rTMS for MDD: 5.5cm Rule vs. F3 Targeting
A study testing Repetitive transcranial magnetic stimulation in people with Major Depressive Disorder and Depression, run by Nicholas Trapp at 1 site in United States.
Trial summary
The purpose of this study is to examine the effects of different treatment locations using repetitive transcranial magnetic stimulation (rTMS) to treat major depressive disorder. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Major Depressive Disorder, Depression
- 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
- 123 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 13 Sep 2022
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of major depressive disorder
- Age between 18 and 90 years
- rTMS is clinically indicated as determined by clinical rTMS physician team at University of Iowa
Who cannot join
- rTMS contraindication such as implanted ferromagnetic material in the head or history of epilepsy with poorly controlled seizures
- MRI exclusion criteria (if participating in MRI portion of study) including implanted device such as:
- Pacemaker
- Coronary Stent
- Defibrillator
- Neurostimulation
Show all 14Show fewer
- Or any of the following conditions:
- Claustrophobia
- Uncontrolled high blood pressure
- Poorly controlled atrial fibrillation
- Significant heart disease
- Hemodynamic instability
- Severe kidney disease
- Pregnant, trying to become pregnant, or breast feeding
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
About this study
Official title: The Effects of Repetitive Transcranial Magnetic Stimulation Prefrontal Target Location on Outcomes for Major Depressive Disorder
The purpose of this study is to examine the effects of different treatment locations using repetitive transcranial magnetic stimulation (rTMS) to treat major depressive disorder.
Read the detailed description
Currently there is little standardization between rTMS treatment programs as to what is the best way to localize the left dorsolateral prefrontal cortex, which is the FDA-approved treatment location for clinical rTMS for major depressive disorder (MDD). Different targeting methods yield locations that can vary by up to a few centimeters. By comparing different treatment locations and obtaining neurobehavioral, neuroimaging, cognitive, and neuropsychological measures, this study would provide the opportunity to identify the optimal treatment targeting method when using rTMS for major depressive disorder in a clinical setting. This study will specifically be focusing on comparing the two most common targeting methods: a target 5.5cm anterior to the motor strip on the left prefrontal scalp and the F3 target location on the left prefrontal scalp as identified using the 10-20 EEG system nomenclature.
- Conditions
- Major Depressive Disorder, Depression
- Being tested
- Repetitive transcranial magnetic stimulation
- Keywords
- Transcranial Magnetic Stimulation, rTMS, F3, 5.5cm rule, Targeting, TMS
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive transcranial magnetic stimulationDevice
Repetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments.
| Study group | Role | What they receive |
|---|---|---|
| 5.5cm Rule Group | Active comparator | rTMS will be targeted at a left prefrontal target 5.5cm anterior to the primary motor strip identified on the scalp during motor threshold testing. Receives: Device: Repetitive transcranial magnetic stimulation |
| F3 Group | Active comparator | rTMS will be targeted at the left prefrontal scalp target identified as F3 according to the 10-20 EEG system. Receives: Device: Repetitive transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change in Patient Health Questionnaire 9-Item Assessment Score
Overall change in total Patient Health Questionnaire 9-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other.
This assessment measures depression severity at baseline. Total scores of 5, 10, 15, and 20 represent markers for mild, moderate, moderately severe, and severe depression, respectively.
All 9 items are summed to compute a total score, ranging from 0-27. Higher scores indicate more severe self-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Percentage Change in Montgomery-Asberg Depression Rating Scale Score
Overall change in total Montgomery-Asberg Depression Rating Scale score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other.
This scale assesses depression severity at baseline. Scores of 8, 17, and 34 are cut-off points for mild, moderate, severe depression, respectively.
This 10 item scale is summed to compute a total score, ranging from 0-60. Higher scores indicate more severe clinician-rated depressive symptoms.
Negative change from baseline implies a decrease in depressive symptoms.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Percentage Change in General Anxiety Disorder 7-Item Assessment Score
Overall change in total General Anxiety Disorder 7-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other.
This assesses anxiety severity as baseline. Scores of 5, 10, and 15 are cut-off points for mild, moderate, and severe anxiety, respectively.
All 7 items are summed to compute a total score, ranging from 0-21. Higher scores indicate more severe self-rated anxiety symptoms.
Negative change from baseline implies a decrease in anxiety symptoms.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment
Comparison of the response rate (>50% improvement) and remission rate (score <5) for the Patient Health Questionnaire 9-Item Assessment between the 2 groups post-treatment.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Response and Remission Rates on Montgomery-Asberg Depression Rating Scale
Comparison of the response rate (>50% improvement) and remission rate (score <10) for the MADRS between the 2 groups post-treatment.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Response Rates on General Anxiety Disorder 7-Item Assessment
Comparison of the response rate (>50% improvement) for the General Anxiety Disorder 7-Item Assessment between the 2 groups post-treatment.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Secondary outcomes (2)
Montreal Cognitive Assessment Score Changes
Change in Montreal Cognitive Assessment scores from baseline to final timepoint. Reported here as the mean difference in total Montreal Cognitive Assessment score from baseline to endpoint.
Montreal Cognitive Assessment is used a screen for cognitive impairment, calculated by adding the points from each task, which range from 0-30.
Higher scores indicate little to no cognitive impairment 26 or above: Normal cognition 18-25: Mild cognitive impairment 10-17: Moderate cognitive impairment Fewer than 10: Severe cognitive impairment
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Emotion Measures
T Score Changes in National Institutes of Health Toolbox Emotional Battery A T score of 50 corresponds to the population mean. Scores may range from 20-80 with a standard deviation of 10. Higher T scores indicate a higher endorsement of each domain. Here, we present changes in mean score from pre-treatment to post-treatment. In that way, a positive value represents a decrease in average T score, and vice versa.
Measured: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2017
- Study start1 May 2018
- Primary completion13 Sep 2022
- Study completion13 Sep 2022
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 Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nicholas Trapp
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nicholas Trapp, University of Iowa
- Investigators
- Nicholas T Trapp, M.D., Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03378570
- Sponsor's protocol ID
- 201709834
- Status last verified
- Jan 2025
- First submitted
- 14 Dec 2017
- Last updated
- 3 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Trapp NT, Pace BD, Neisewander B, Ten Eyck P, Boes AD. A randomized trial comparing beam F3 and 5.5 cm targeting in rTMS treatment of depression demonstrates similar effectiveness. Brain Stimul. 2023 Sep-Oct;16(5):1392-1400. doi: 10.1016/j.brs.2023.09.006. Epub 2023 Sep 14.
PubMed 37714408
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Repetitive Transcranial Magnetic Stimulation Prefrontal Target Location on Outcomes for Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT03378570
- Acronym / sponsor ID
- 201709834
- Conditions
- Major Depressive Disorder, Depression
- Keywords
- Transcranial Magnetic Stimulation, rTMS, F3, 5.5cm rule, Targeting, TMS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Nicholas TrappUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 13 Sep 2022 (actual)
- Study completion
- 13 Sep 2022 (actual)
- First posted
- 20 Dec 2017 (actual)
- Results
- Posted 3 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the effects of different treatment locations using repetitive transcranial magnetic stimulation (rTMS) to treat major depressive disorder.
Detailed description
Currently there is little standardization between rTMS treatment programs as to what is the best way to localize the left dorsolateral prefrontal cortex, which is the FDA-approved treatment location for clinical rTMS for major depressive disorder (MDD). Different targeting methods yield locations that can vary by up to a few centimeters. By comparing different treatment locations and obtaining neurobehavioral, neuroimaging, cognitive, and neuropsychological measures, this study would provide the opportunity to identify the optimal treatment targeting method when using rTMS for major depressive disorder in a clinical setting. This study will specifically be focusing on comparing the two most common targeting methods: a target 5.5cm anterior to the motor strip on the left prefrontal scalp and the F3 target location on the left prefrontal scalp as identified using the 10-20 EEG system nomenclature.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5.5cm Rule Group | Active comparator | Device: Repetitive transcranial magnetic stimulationrTMS will be targeted at a left prefrontal target 5.5cm anterior to the primary motor strip identified on the scalp during motor threshold testing. |
| F3 Group | Active comparator | Device: Repetitive transcranial magnetic stimulationrTMS will be targeted at the left prefrontal scalp target identified as F3 according to the 10-20 EEG system. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of major depressive disorder
- Age between 18 and 90 years
- rTMS is clinically indicated as determined by clinical rTMS physician team at University of Iowa
Key exclusion criteria (14 listed)
- rTMS contraindication such as implanted ferromagnetic material in the head or history of epilepsy with poorly controlled seizures
- MRI exclusion criteria (if participating in MRI portion of study) including implanted device such as:
- Pacemaker
- Coronary Stent
- Defibrillator
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 stimulationRepetitive transcranial magnetic stimulation will be targeted to a location in the left prefrontal cortex and delivered according to FDA-approved parameters for the treatment of major depressive disorder, specifically high-frequency 10 Hz rTMS for 3000 pulses, 5 days per week for a total number of sessions as deemed clinically appropriate by the patient's clinical TMS treatment team but usually on the order of 20-30 treatments. | Device | 5.5cm Rule Group, F3 Group |
Primary outcome
Percentage Change in Patient Health Questionnaire 9-Item Assessment Score
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Overall change in total Patient Health Questionnaire 9-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assessment measures depression severity at baseline. Total scores of 5, 10, 15, and 20 represent markers for mild, moderate, moderately severe, and severe depression, respectively. All 9 items are summed to compute a total score, ranging from 0-27. Higher scores indicate more severe self-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Percentage Change in Montgomery-Asberg Depression Rating Scale Score
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Overall change in total Montgomery-Asberg Depression Rating Scale score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This scale assesses depression severity at baseline. Scores of 8, 17, and 34 are cut-off points for mild, moderate, severe depression, respectively. This 10 item scale is summed to compute a total score, ranging from 0-60. Higher scores indicate more severe clinician-rated depressive symptoms. Negative change from baseline implies a decrease in depressive symptoms.
Percentage Change in General Anxiety Disorder 7-Item Assessment Score
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Overall change in total General Anxiety Disorder 7-Item Assessment score from pre to post-treatment assessment, comparing results of 2 active groups to assess for superiority of one treatment to the other. This assesses anxiety severity as baseline. Scores of 5, 10, and 15 are cut-off points for mild, moderate, and severe anxiety, respectively. All 7 items are summed to compute a total score, ranging from 0-21. Higher scores indicate more severe self-rated anxiety symptoms. Negative change from baseline implies a decrease in anxiety symptoms.
Response and Remission Rates on Patient Health Questionnaire 9-Item Assessment
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Comparison of the response rate (>50% improvement) and remission rate (score <5) for the Patient Health Questionnaire 9-Item Assessment between the 2 groups post-treatment.
Response and Remission Rates on Montgomery-Asberg Depression Rating Scale
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Comparison of the response rate (>50% improvement) and remission rate (score <10) for the MADRS between the 2 groups post-treatment.
Response Rates on General Anxiety Disorder 7-Item Assessment
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Comparison of the response rate (>50% improvement) for the General Anxiety Disorder 7-Item Assessment between the 2 groups post-treatment.
2 secondary outcomes
Montreal Cognitive Assessment Score Changes
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Emotion Measures
Time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37714408Trapp NT, Pace BD, Neisewander B, Ten Eyck P, Boes AD. A randomized trial comparing beam F3 and 5.5 cm targeting in rTMS treatment of depression demonstrates similar effectiveness. Brain Stimul. 2023 Sep-Oct;16(5):1392-1400. doi: 10.1016/j.brs.2023.09.006. Epub 2023 Sep 14.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicholas T Trapp, M.D. principal investigator
University of Iowa
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 Major Depressive Disorder and Depression, run by Nicholas Trapp 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 14 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 3 Feb 2025. 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 3 Feb 2025). 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?
Percentage Change in Patient Health Questionnaire 9-Item Assessment Score (time frame: Pre-assessment will be obtained within approximately 1 week of starting rTMS. Post-assessment will be obtained immediately following completion of rTMS course, usually 4-6 weeks later.). The study lists 6 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 NCT03378570, 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 3 Feb 2025; AzTrials last refreshed its copy on 30 Oct 2026.