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fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI

Primary Purpose

Major Depressive Disorder, Traumatic Brain Injury

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Active

Sham

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring rTMS

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Adults age 18 to 65
History of traumatic brain injury (TBI) at least two weeks prior to study initiation
Presence of an active major depressive episode as defined by DSM-5 criteria, including depression secondary to traumatic brain injury
Baseline score of 10 or greater on Montgomery-Asberg Depression Rating Scale (MADRS)
Failure of at least one prior antidepressant trial after the traumatic brain injury

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
Depression secondary to a general medical illness, with the exception of TBI
Dysphoria better explained by a baseline personality disorder than a major depressive episode
Dysphoria better explained by a baseline anxiety disorder (including post-traumatic stress disorder) rather than a major depressive episode
Active suicidal ideation

Contraindications to rTMS treatment:

Seizure disorder
Significantly elevated seizure risk, as determined by clinician assessment
TBI associated with elevated seizure risk, including penetrating injury and/or cortical intraparenchymal hemorrhage
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

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active rTMS

Sham/crossover rTMS

Arm Description

Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.

Rather than receiving active treatment, subjects will receive sham treatment designed to be indistinguishable from active treatment to the patient. After completion of the sham course, patients will have the option to receive open-label active treatment at no cost.

Outcomes

Primary Outcome Measures

Improvement in depressive symptoms

This will be measured as the mean percentage change in baseline scores on Montgomery-Asberg Depression Rating Scale (MADRS) before treatment and immediately after the 4-week treatment period.

Secondary Outcome Measures

Changes in resting-state fMRI and DTI findings

MRI imaging will be conducted to assess resting-state functional connectivity using functional magnetic resonance imaging (fMRI). More detailed structural (DTI) and functional (fMRI) imaging will be measured in a subgroup of patients.

Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries

The NIH Toolbox Cognitive battery will be used to determine change in cognitive symptoms with treatment. Emotional battery and TBI-QoL scales will be used to determine change in general neuropsychiatric symptom burden.

Changes in temperament and character

Will administer the 140-question Temperament and Character Inventory (TCI-R140) before and after treatment.

Response and remission rates in depressive symptoms

Percentage of subjects achieving response (>50% improvement in MADRS) and remission (final MADRS score <7) before treatment and immediately after the 4-week treatment period.

Changes in headache scales

Mean percentage improvement in HIT-6 headache scores

Changes in tinnitus score

Mean percentage improvement in tinnitus severity score and mini-Tinnitus Questionnaire scores

Full Information

NCT ID

NCT02980484

First Posted

February 25, 2016

Last Updated

March 26, 2018

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT02980484

Brief Title

fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI

Official Title

fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Terminated

Why Stopped

Investigators left the institution for unrelated reasons

Study Start Date

August 2016 (undefined)

Primary Completion Date

August 2017 (Actual)

Study Completion Date

August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This pilot study aims to investigate the efficacy of fMRI-targeted repetitive transcranial magnetic stimulation (rTMS) in treatment of major depression associated with traumatic brain injury (TBI). Half of patients will receive active treatment, while the other will receive a sham treatment with the option of receiving open-label active treatment afterwards.

Detailed Description

rTMS is an FDA-approved treatment for major depressive disorder, but its utility has not yet been investigated for major depression associated with traumatic brain injury. This will be a prospective double-blind randomized sham-controlled crossover study. Patients in the treatment group will receive 20 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC) and low-frequency rTMS over the right DLPFC. The DLPFC will be identified as target by using individual subject-level resting state network estimation (Hacker et al, 2013). Patients in the control group will receive 20 sham treatments designed to be visibly indistinguishable from active treatment, and will subsequently have the option to be crossed over to receive active treatment with the aforementioned protocol. A subgroup of patients in each group will receive more detailed diffusion imaging (diffusion tensor and diffusion kurtosis imaging) and resting state fMRI scans before and after the treatment in order to assess for changes in white matter integrity and functional connectivity associated with the treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder, Traumatic Brain Injury

Keywords

rTMS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

Randomized double-blind sham-controlled trial with an optional open-label crossover extension for subjects randomized to sham group.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active rTMS

Arm Type

Experimental

Arm Description

Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above.

Arm Title

Sham/crossover rTMS

Arm Type

Sham Comparator

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Active

Intervention Description

Repetitive transcranial magnetic stimulation (rTMS) will be applied to the left dorsolateral prefrontal cortex (DLPFC) (4000 pulses, 10 Hz, 5-sec trains, 25-sec inter-train interval) followed by the right DLPFC (1000 pulses, 1 Hz frequency, single train). The DLPFC will be identified using individual subject-level resting-state network estimation (Hacker et al, 2013). Each treatment will be completed over the course of 1 hour, and each subject will receive a total of 20 treatments over the course of 20 consecutive weekdays.

Intervention Type

Procedure

Intervention Name(s)

Sham

Intervention Description

Treatment that looks and feels similar to active rTMS will be administered as a sham treatment.

Primary Outcome Measure Information:

Title

Improvement in depressive symptoms

Description

This will be measured as the mean percentage change in baseline scores on Montgomery-Asberg Depression Rating Scale (MADRS) before treatment and immediately after the 4-week treatment period.

Time Frame