Symptom-specific TMS Targets for Depression and Anxiety

• ClinicalTrials.gov Identifier: NCT04604210
• Recruitment Status: Recruiting
• First Posted: October 27, 2020
• Last Update Posted: August 3, 2022
• Sponsor: Brigham and Women's Hospital
• Information provided by (Responsible Party): Shan Siddiqi, MD, Brigham and Women's Hospital

Study Description

Brief Summary:

This pilot study aims to compare two different treatment targets for transcranial magnetic stimulation, an FDA-approved treatment for major depressive disorder (MDD), in terms of their relative efficacy for depression versus anxiety.

Condition or disease	Intervention/treatment	Phase
Depression; Anxiety; Major Depressive Disorder	Procedure: Transcranial magnetic stimulation	Phase 2

Detailed Description:

Transcranial magnetic stimulation (TMS) is a safe, noninvasive FDA-cleared technique that is commonly used as a treatment for MDD. It has been shown to focally activate specific brain regions that are believed to be underactive in these patients. This study aims to compare two different TMS targets in the prefrontal cortex. TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.

This will be a prospective double-blind randomized controlled trial to assess the comparative efficacy of two different TMS targets within the prefrontal cortex (PFC). The "dysphoric" target in the dorsolateral PFC is believed to be more effective for depression, while the "anxiosomatic" target in the dorsomedial PFC is believed to be more effective for anxiety.

Patients with comorbid depression and anxiety will receive 6 weeks of TMS following standard clinical parameters (30 treatments over 6 weeks, 10 Hz frequency, 3000 pulses) with MRI-guided neuronavigation. Participants will be randomized to either the dysphoric or anxiosomatic target. Both targets are believed to be effective treatments for this patient population. Participants and raters will remain blinded to the group assignment. All participants will receive resting-state functional MRI scans before and after the course of treatment in order to study physiological changes.

The dysphoric target is expected to induce greater relative improvement in depression, while the anxiosomatic target is expected to induce greater relative improvement in anxiety.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Parallel-group double-blind randomized, controlled trial
• Masking: Triple (Participant, Investigator, Outcomes Assessor)

Masking Description

Participants will be blinded to which target is expected to improve which symptom.

Study investigators (with the exception of the treatment administrator), including the outcomes assessor, will be blinded to which participant is receiving which treatment.

• Primary Purpose: Treatment
• Official Title: A Pilot Randomized Trial of Distinct Symptom-specific Targets for Transcranial Magnetic Stimulation in Patients With Depression and Anxiety
• Actual Study Start Date: February 3, 2021
• Estimated Primary Completion Date: November 1, 2023
• Estimated Study Completion Date: January 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dysphoric target; The "dysphoric" target is a region in the dorsolateral prefrontal cortex. TMS targeted to this region has been shown to be more effective for depression than anxiety.	Procedure: Transcranial magnetic stimulation; Transcranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression. It has been shown to focally activate specific brain regions that are believed to be underactive in patients suffering from depression. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.; Other Name: TMS
Experimental: Anxiosomatic target; The "anxiosomatic" target is a region in the dorsomedial prefrontal cortex. TMS targeted to this region has been shown to be more effective for anxiety than depression.	Procedure: Transcranial magnetic stimulation; Transcranial magnetic stimulation (TMS) is a noninvasive FDA-approved technique that is commonly used as a treatment for depression. It has been shown to focally activate specific brain regions that are believed to be underactive in patients suffering from depression. In this study, TMS will be administered within FDA-approved guidelines under the supervision of a physician with experience in administering the treatment and monitoring for complications.; Other Name: TMS

Outcome Measures

Primary Outcome Measures :

1. Beck Depression Inventory (BDI) [ Time Frame: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments) ]
   The primary outcome will be the rank-transformed ratio of BDI change to BAI change
2. Beck Anxiety Inventory (BAI) [ Time Frame: Baseline (before treatment), 3 weeks (after 15 treatments), and 6 weeks (after 30 treatments) ]
   The primary outcome will be the rank-transformed ratio of BDI change to BAI change

Secondary Outcome Measures :

1. Resting-state functional MRI (rsfMRI) scan [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   Functional MRI scan will be conducted before and after treatment in order to assess for treatment-induced changes in brain connectivity
2. Temperament and Character Inventory, Revised 140-item (TCI-R 140) [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   Psychobiologically-based personality inventory which measures seven personality dimensions (harm avoidance, novelty seeking, reward dependence, persistence, self-directedness, cooperativeness, and persistence). For each dimension, this yields a scaled T-score (mean score of 50 with standard deviation of 10). This is an overall estimate of personality traits, and there are no "better" or "worse" traits.
3. NIH Toolbox cognitive battery [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   An interactive computerized battery of cognitive tasks which is used to compute an overall index of crystallized and fluid cognition. For each cognitive subscale, this yields a scaled T-score (mean score of 100 with standard deviation of 10).
4. Multidimensional task-based emotional assessment [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   An interactive computerized battery of emotional tasks, including Aversion-Reward Conflict, Emotion Conflict Resolution, Multiple Source Interference, Fear Conditioning/Extinction, Gambling, and Associative Learning Tasks. Each task will yield results for accuracy and reaction time.
5. Pain at the stimulation site [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   Participants will be asked to rate treatment-induced pain/discomfort on a scale of 1 to 10
6. Multidimensional battery of emotional questionnaires [ Time Frame: Baseline (before treatment) and 6 weeks (after 30 treatments) ]
   A computerized battery of questionnaires including the Anxiety Sensitivity Index, Adult Temperament Questionnaire, Emotion Reactivity Scale, Barratt Impulsivity Scale, Adult ADHD Self-Rating Scale, Brief Inventory of Executive Functioning. Each scale yields a raw score.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adults age 18 to 65
• Meeting FDA guidelines for clinical TMS (DSM-5 diagnosis of major depressive disorder with at least one failed antidepressant trial)1
• Beck Depression Inventory (BDI) score of 20 or higher
• Beck Anxiety Inventory (BAI) score of 16 or higher

Exclusion Criteria:

• History of:

  • Moderate or severe substance use disorder in the past six months as defined by DSM-5 criteria, with the exception of cannabis and nicotine use disorders.
  • Dementia, as defined by treating neurologist
  • Moderate or severe autism spectrum disorder
  • Bipolar disorder
  • Schizophrenia spectrum disorders

• Current evidence of:

  • Substance-induced mood disorder
  • Active psychotic symptoms
  • Active suicidal ideation

• Contraindications to rTMS treatment:

  • Seizure disorder
  • Significantly elevated seizure risk, as determined by clinician assessment
  • Presence of metallic objects within the head
  • Presence of an implanted neurostimulation device within the head

• Contraindications to MRI

  • Severe claustrophobia
  • Severe pain/illness exacerbated by lying prone in the scanner
  • Presence of non-MRI compatible metal foreign bodies or implants
  • Weight in excess of 350 lbs
  • Shoulder width in excess of maximum tolerable width for scanner

Contacts and Locations

Contacts

Contact: Christopher Lin, BS; 6175251218; bwhtmstrials@bwh.harvard.edu

Locations

United States, Massachusetts

Brigham & Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Christopher Lin, BS

Sponsors and Collaborators

Brigham and Women's Hospital

Investigators

• Principal Investigator: Shan H Siddiqi, MD; Brigham and Women's Hospital

More Information

• Responsible Party: Shan Siddiqi, MD, Assistant Professor, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04604210
• Other Study ID Numbers: 2020P002296
• First Posted: October 27, 2020
• Last Update Posted: August 3, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: De-identified survey response data and/or neuroimaging data may be shared with collaborators for further analysis.

• 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.: Yes

Keywords provided by Shan Siddiqi, MD, Brigham and Women's Hospital:

TMS; Transcranial; Neuromodulation; Brain stimulation; Depression; Anxiety

Additional relevant MeSH terms:

Depression; Depressive Disorder; Anxiety Disorders; Depressive Disorder, Major; Behavioral Symptoms; Mood Disorders; Mental Disorders