Accelerated TMS to a Novel Brain Target in MDD and PTSD

NCT03114891 | Completed Results DMC FDA Device

• 1 other identifier: 826007
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Post Traumatic Stress Disorder; Major Depressive Disorder

Keywords

post-traumatic stress; depression; ptsd; tms

Outcome Measures

Primary Outcomes (1)

• Percent Change in Depression Severity of TMS at fMRI-guided Brain Target vs Standard Brain Target

  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)

Study Arms (4)

First Round: fMRI-guided Target/Video, Second Round: 6cm Target/Task

EXPERIMENTAL

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); Behavioral: Task; Procedure: fMRI-guided TMS target

First Round: 6cm Target/Video, Second Round: fMRI-guided Target/Task

EXPERIMENTAL

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); Behavioral: Task; Procedure: fMRI-guided TMS target

First Round: fMRI-guided Target/Task, Second Round: 6cm Target/Video

EXPERIMENTAL

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); Behavioral: Task; Procedure: fMRI-guided TMS target

First Round: 6cm Target/Task, Second Round: fMRI-guided Target/Task

EXPERIMENTAL

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); Behavioral: Task; Procedure: fMRI-guided TMS target

Interventions

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. In this study, we used administered theta burst TMS stimulation.

First Round: 6cm Target/Task, Second Round: fMRI-guided Target/Task; First Round: 6cm Target/Video, Second Round: fMRI-guided Target/Task; First Round: fMRI-guided Target/Task, Second Round: 6cm Target/Video; First Round: fMRI-guided Target/Video, Second Round: 6cm Target/Task

Task BEHAVIORAL

Subject completes a working memory task (Letter Nback) between the two rounds of theta burst stimulation.

First Round: 6cm Target/Task, Second Round: fMRI-guided Target/Task; First Round: 6cm Target/Video, Second Round: fMRI-guided Target/Task; First Round: fMRI-guided Target/Task, Second Round: 6cm Target/Video; First Round: fMRI-guided Target/Video, Second Round: 6cm Target/Task

fMRI-guided TMS target PROCEDURE

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.

First Round: 6cm Target/Task, Second Round: fMRI-guided Target/Task; First Round: 6cm Target/Video, Second Round: fMRI-guided Target/Task; First Round: fMRI-guided Target/Task, Second Round: 6cm Target/Video; First Round: fMRI-guided Target/Video, Second Round: 6cm Target/Task

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Cures Within Reach: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Chen AC, Oathes DJ, Chang C, Bradley T, Zhou ZW, Williams LM, Glover GH, Deisseroth K, Etkin A. Causal interactions between fronto-parietal central executive and default-mode networks in humans. Proc Natl Acad Sci U S A. 2013 Dec 3;110(49):19944-9. doi: 10.1073/pnas.1311772110. Epub 2013 Nov 18.

  PMID: 24248372 BACKGROUND

• Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

  PMID: 15664172 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Depressive Disorder, Major; Depression

Interventions

Transcranial Magnetic Stimulation; potassium channel subfamily K member 3

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Desmond Oathes, Principal Investigator
• Organization: University of Pennsylvania

oathes@pennmedicine.upenn.edu

215-573-9390

Study Officials

• Desmond Oathes, Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: The patients will be blinded as to whether or not their site of stimulation is based on the standard targeting method or our novel fMRI-guided targeting method. In addition, staff members administering TMS will not know if the site of stimulation was created based on the standard targeting method or novel fMRI method.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a randomized study. All subjects will receive active TMS, so there is no placebo or sham condition. However, the patients will be blinded as to whether or not their site of stimulation is based on the standard targeting method or our novel fMRI-guided targeting method. TMS is administered over to one of these two sites over a two week period, and then TMS will be administered to the other site over a subsequent two-week period. All subjects will receive TMS to both sites as a part of the study, but the order is randomized and counterbalanced.

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: April 14, 2017
• Study Start: April 20, 2017
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)