Major Depressive DisorderPhase 2NCT02980484
fMRI-neuronavigated rTMS for the Treatment of Major Depression Associated With TBI
A Phase 2 study testing Active in people with Major Depressive Disorder and Traumatic Brain Injury, run by Washington University School of Medicine at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Traumatic Brain Injury
- What is being tested?
- Active
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Aug 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 25Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury
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.
Read the 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
- Being tested
- Active, Sham
- Keywords
- rTMS
- Medical subject headings
- Depressive Disorder, Major, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ActiveProcedure or surgery
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.
ShamProcedure or surgery
Treatment that looks and feels similar to active rTMS will be administered as a sham treatment.
| Study group | Role | What they receive |
|---|---|---|
| Active rTMS | Experimental | Subjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above. Receives: 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. Receives: Procedure: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Secondary outcomes (6)
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.
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
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.
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in temperament and character
Will administer the 140-question Temperament and Character Inventory (TCI-R140) before and after treatment.
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
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.
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in headache scales
Mean percentage improvement in HIT-6 headache scores
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in tinnitus score
Mean percentage improvement in tinnitus severity score and mini-Tinnitus Questionnaire scores
Measured: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study startAug 2016
- Primary completionAug 2017
- Study completionAug 2017
Why it stopped: Investigators left the institution for unrelated reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomized double-blind sham-controlled trial with an optional open-label crossover extension for subjects randomized to sham group.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shan H Siddiqi, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02980484
- Sponsor's protocol ID
- 201603051
- Status last verified
- Mar 2018
- First submitted
- 25 Feb 2016
- Last updated
- 29 Mar 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: De-identified neuroimaging data will be submitted to FITBIR (Federal Interagency TBI Research)
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- fMRI-neuronavigated Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depression Associated With Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02980484
- Acronym / sponsor ID
- 201603051
- Conditions
- Major Depressive Disorder, Traumatic Brain Injury
- Keywords
- rTMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigators left the institution for unrelated reasons
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Aug 2016
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 2 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized double-blind sham-controlled trial with an optional open-label crossover extension for subjects randomized to sham group.
| Arm | Type | Receives |
|---|---|---|
| Active rTMS | Experimental | Procedure: ActiveSubjects will receive a full course of 20 rTMS treatments over 20 consecutive weekdays as described above. |
| Sham/crossover rTMS | Sham comparator | Procedure: ShamRather 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ActiveRepetitive 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. | Procedure or surgery | Active rTMS |
| ShamTreatment that looks and feels similar to active rTMS will be administered as a sham treatment. | Procedure or surgery | Sham/crossover rTMS |
Primary outcome
Improvement in depressive symptoms
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
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.
6 secondary outcomes
Changes in resting-state fMRI and DTI findings
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in NIH Toolbox Cognitive, Emotional, and Quality of Life batteries
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in temperament and character
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Response and remission rates in depressive symptoms
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in headache scales
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Changes in tinnitus score
Time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)
Results and safety
The study was stopped early (reason given: Investigators left the institution for unrelated reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
- Individual participant dataSharing planned: Yes. De-identified neuroimaging data will be submitted to FITBIR (Federal Interagency TBI Research)
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shan H Siddiqi, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Active in people with Major Depressive Disorder and Traumatic Brain Injury, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Investigators left the institution for unrelated reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in depressive symptoms (time frame: Difference between pre-treatment (baseline) and post-treatment (4 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2018.