Accelerated TMS to a Novel Brain Target in MDD and PTSD

April 13, 2023 updated by: University of Pennsylvania
This is a Clinical Trial designed to evaluate novel transcranial magnetic stimulation (TMS) methods for treating depression/PTSD. TMS is an FDA-approved procedure for treatment-resistant depression. The use of the stimulation in this current study is considered experimental. The purpose of this research study is to compare the effects of TMS at two different brain regions. This information will help the investigators to determine which treatment strategies provide the greatest clinical benefit to patients. Results of the study will provide brain and behavior measures for future work, which may be critical to developing effective disease markers and novel treatments for psychiatric conditions.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Non-invasive transcranial magnetic stimulation (TMS) is now FDA-approved for the treatment of major depressive disorder (MDD). However, there is growing evidence that the targeting strategy for delivering TMS treatment would yield superior clinical outcomes if it were more tailored to individual neuroanatomy. The current study take this idea one step further and suggest that functional MRI guided TMS might yield an even greater leap forward in promoting optimal clinical outcomes.

The sgACC has been well established as a brain area sensitive to negative mood inductions and implicated in neural abnormalities associated with affective and stress disorders. It is therefore one of the primary targets for deep brain stimulation (DBS) treatment of MDD using surgically implanted DBS devices. Recent posthoc imaging studies of patients who have undergone TMS treatment for depression suggest that treatment outcomes tended to be better when patients were by chance stimulated in an area of lateral prefrontal cortex that had high levels of functional connectivity with sgACC. Based on this finding and on interleaved TMS/fMRI probe data, the investigators contend that targeting delivery of TMS to the brain surface non-invasively as indicated by sgACC resting functional connectivity may be especially effective in downregulating sgACC and thereby producing superior clinical outcomes.

Researchers have used TMS/fMRI to better understand causal communication among circuits typically examined with resting fMRI alone. Recent work suggests that there are specific sites that, when stimulated, influence subcortical brain areas implicated in affective disorders such as the sgACC. Previously, TMS targets were based on brain atlases mapped onto individual brain surfaces. This proposal will utilize more individualized targeting from participants' own resting connectivity data to guide stimulation that we show is especially effective in influencing downstream brain areas of interest. The investigators will focus on a target region of the lateral prefrontal cortex (LPFC) that data suggest is particularly effective at influencing the sgACC. As an alternative brain target, we will also test the efficacy of the dorsolateral prefrontal cortex as a target given its precedence in the literature as an effective stimulation site for remediating depressive symptoms. The target will be chosen based on an atlas and will adjust the target coordinates based on the inverse of a nonlinear normalization of each participant's brain to standard brain space. Thus, individual anatomical differences will be taken account with this target though without guidance from individual functional imaging data.

To increase generalizability to other disorders and to patients with comorbid anxiety and depression (the typical clinical profile), the investigators will recruit patients who are diagnosed PTSD and have symptoms of depression or those who experience trauma-induced MDD. Participants will be scanned in an MRI to get anatomical and resting fMRI data to guide TMS, then participants will be invited to participate in two rounds of two week TMS treatment to each site (order counterbalanced) with one month between treatments. Participants will be monitored to assess PTSD symptoms, depressive symptoms,and quality of life before, acutely after, and one month following TMS treatments to evaluate the effectiveness of each site in mitigating symptoms or improving functioning.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 60 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 18-60 years old, male or female, any race
  2. Patients must currently meet sufficient DSM criteria for PTSD and have symptoms of depression; or meet criteria for trauma-induced MDD
  3. Capacity to give informed consent and follow study procedures
  4. English speaking

Exclusion Criteria:

  1. Outside age range
  2. Patient does not meet sufficient DSM criteria for PTSD or MDD
  3. Psychiatric medication use
  4. Significant handicaps (e.g. mental handicap) that would interfere with testing procedures
  5. MRI contraindications
  6. Additional TMS contraindications
  7. Medication use that substantially reduces seizure threshold to TMS (olanzapine, chlorpromazine, lithium)
  8. Opiate medication
  9. Known neurological disorders including multiple sclerosis, encephalopathy, seizure disorder, brain tumors
  10. Current alcohol or substance abuse disorder (moderate or severe)
  11. Current schizophrenia or other psychotic disorder, or current bipolar disorder
  12. Refusal to abstain from illicit drug use for the duration of the study
  13. Refusal to abstain from alcohol within 24 hours of the MRI scan
  14. Pregnancy
  15. Newly initiated psychotherapy (less than 6 weeks)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: First Round: fMRI-guided Target/Video, Second Round: 6cm Target/Task

First round: This site of stimulation will be created from participants' individualized resting connectivity data. We will identify a cortical target in the left prefrontal cortex (LPFC) that influences the subgenual anterior cingulate cortex (sgACC). Two daily sessions (~10min apart) of intermittent theta-burst stimulation will be administered to this fMRI-guided target for 10 consecutive weekdays. Between the two iTBS sessions, participants will watch a relaxing nature video.

Second round: After 3 weeks, participants will undergo another set of two daily iTBS sessions for 10 consecutive weekdays to their 'standard' target (6cm anterior of their hand knob). Between the two iTBS sessions, participants will complete a working memory task.
Device: 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. In this study, we used administered theta burst TMS stimulation.
Behavioral: Task
Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.
Procedure: fMRI-guided TMS target
Administration of TMS to individualized targeting from the participant's fMRI scans. Our preliminary data suggest this target region is particularly effective at influencing the sgACC.
Experimental: First Round: 6cm Target/Video, Second Round: fMRI-guided Target/Task

First round: This 'standard' target will be identified by measuring 6cm anterior of the hand knob. Two daily sessions (~10min apart) of intermittent theta-burst stimulation will be administered to this to this target for 10 consecutive weekdays. Between the two iTBS sessions, participants will watch a relaxing nature video.

Second round: After 3 weeks, participants will undergo another set of two daily iTBS sessions for 10 consecutive weekdays to their fMRI-guided target (cortical target influencing sgACC). Between the two iTBS sessions, participants will complete a working memory task.
Device: 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. In this study, we used administered theta burst TMS stimulation.
Behavioral: Task
Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.
Procedure: fMRI-guided TMS target
Administration of TMS to individualized targeting from the participant's fMRI scans. Our preliminary data suggest this target region is particularly effective at influencing the sgACC.
Experimental: First Round: fMRI-guided Target/Task, Second Round: 6cm Target/Video

First round: This site of stimulation will be created from participants' individualized resting connectivity data. We will identify a cortical target in the left prefrontal cortex (LPFC) that influences the subgenual anterior cingulate cortex (sgACC). Two daily sessions (~10min apart) of intermittent theta-burst stimulation will be administered to this fMRI-guided target for 10 consecutive weekdays. Between the two iTBS sessions, participants will complete a working memory task.

Second round: After 3 weeks, participants will undergo another set of two daily iTBS sessions for 10 consecutive weekdays to their 'standard' target (6cm anterior of their hand knob). Between the two iTBS sessions, participants will watch a relaxing nature video.
Device: 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. In this study, we used administered theta burst TMS stimulation.
Behavioral: Task
Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.
Procedure: fMRI-guided TMS target
Administration of TMS to individualized targeting from the participant's fMRI scans. Our preliminary data suggest this target region is particularly effective at influencing the sgACC.
Experimental: First Round: 6cm Target/Task, Second Round: fMRI-guided Target/Task

First round: This 'standard' target will be identified by measuring 6cm anterior of the hand knob. Two daily sessions (~10min apart) of intermittent theta-burst stimulation will be administered to this to this target for 10 consecutive weekdays. Between the two iTBS sessions, participants will complete a working memory task.

Second round: After 3 weeks, participants will undergo another set of two daily iTBS sessions for 10 consecutive weekdays to their fMRI-guided target (cortical target influencing sgACC). Between the two iTBS sessions, participants will watch a relaxing nature video.
Device: 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. In this study, we used administered theta burst TMS stimulation.
Behavioral: Task
Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.
Procedure: fMRI-guided TMS target
Administration of TMS to individualized targeting from the participant's fMRI scans. Our preliminary data suggest this target region is particularly effective at influencing the sgACC.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Change in Depression Severity of TMS at fMRI-guided Brain Target vs Standard Brain Target
Time Frame: Before and after the first round of two weeks of TMS treatment (two daily iTBS sessions over 10 consecutive weekdays)

We used the Montgomery-Asberg Depression Rating Scale (MADRS) to measure depression severity after TMS at fMRI-guided brain target vs standard brain target. The MADRS is clinician-rated and consists of 10 items; each item is rated on a 0-6 scale, resulting in a maximum total score of 60 points. Higher MADRS score indicates more severe depression.

For this outcome, we calculated the change (percent decrease) from the participant's baseline MADRS score to their MADRS score after the first round of TMS (to either fMRI-guided brain target or standard brain target). If the outcome is positive, there was a reduction in the MADRS total score, or a reduction in the presence of depressive symptoms after TMS. If the change is negative, there was an increase in the MADRS total score, or an increase in the presence of depressive symptoms after TMS.

Higher positive values means better outcome (or more symptom reduction).
Before and after the first round of two weeks of TMS treatment (two daily iTBS sessions over 10 consecutive weekdays)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation between resting-state connectivity and degree of clinical change
Time Frame: Baseline through study completion, approximately 7 weeks
Correlation between resting-state connectivity prior to TMS and the degree of clinical change in response to TMS treatment targeting this circuit
Baseline through study completion, approximately 7 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cures Within Reach

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Desmond Oathes, Ph.D., University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 20, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 4, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 10, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2017

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 4, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 13, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 826007

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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