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

NCT ID: NCT02980484

Last Updated: 2018-03-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2017-08-31

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.

Conditions

Major Depressive Disorder; Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active rTMS

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

Group Type: EXPERIMENTAL

Active

Intervention Type: PROCEDURE

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.

Sham/crossover rTMS

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.

Group Type: SHAM_COMPARATOR

Sham

Intervention Type: PROCEDURE

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

Interventions

Active

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

Sham

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

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shan H Siddiqi, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

201603051

Identifier Type: -

Identifier Source: org_study_id