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

NCT02980484 | Terminated Phase 2

• 1 other identifier: 201603051
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Traumatic Brain Injury

Keywords

rTMS

Outcome Measures

Primary Outcomes (1)

• 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.

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

Secondary Outcomes (6)

• Changes in resting-state fMRI and DTI findings

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

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

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

• Changes in temperament and character

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

• Response and remission rates in depressive symptoms

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

• Changes in headache scales

  Difference between pre-treatment (baseline) and post-treatment (4 weeks)

Study Arms (2)

Active rTMS

EXPERIMENTAL

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

Procedure: Active

Sham/crossover rTMS

SHAM COMPARATOR

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.

Procedure: Sham

Interventions

Active 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.

Active rTMS

Sham PROCEDURE

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

Sham/crossover rTMS

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Brain Injuries, Traumatic

Interventions

Exercise; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Shan H Siddiqi, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: December 2, 2016
• Study Start: August 1, 2016
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: March 29, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)