Treatment of Depression With Connectivity Guided Robotically Delivered rTMS

Major Depressive Disorder Clinical Trial

Official title:

Treatment of Depression With Connectivity Guided Robotically Delivered Repetitive Transcranial Magnetic Stimulation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02802293
• Other study ID #: HSC20160129H
• Secondary ID: HSC20160129H
• Status: Terminated
• Phase: N/A
• Start date: August 17, 2017
• Est. completion date: March 23, 2021

Study information

• Verified date: June 2022
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the clinical effects (if any) of connectivity-guided repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD) to provide clues about the ideal neural networks to target for more robust clinical outcomes, and to identify potential biomarkers of treatment response including changes in brain network connectivity.

Description:

The investigators propose a randomized, double-blind, 4-week trial of TMS to the left dorsolateral prefrontal cortex (DLPFC) for subjects with MDD all of whom at the patient's treatment clinic are concurrently receiving pharmaceutical and psychotherapeutic interventions. Arm 1 delivers active rTMS to the left DLPFC using the standard aiming strategy. Arm 2 delivers active rTMS to the left anterior DLPFC using connectivity-based, image-guided aiming. Arm 3 delivers active rTMS to the left posterior DLPFC using connectivity-based, image-guided aiming. In all three arms, rTMS is administered in an image-guided, robotically-positioned TMS (irTMS) manner to ensure therapist blinding and equivalent subject experiences across arms. In all three arms, the following stimulation protocol will be used: 10 Hz irTMS delivered in 4 sec trains with 26 sec inter-train intervals, 37.5 minutes/session (i.e. 3,000 pulses/session), 5 sessions/week, for 4 weeks. Neuroimaging will be used both for treatment planning and to characterize any TMS-induced network plasticity using resting-state functional magnetic resonance imaging (rs-fMRI) at week 4 of each treatment arm. Clinical assessments will be administered weekly throughout treatment (weeks 1-4) at the patient's treatment clinic. Additional psychological tests will be performed at UT Health-San Antonio's Research Imaging Institute (RII) at the baseline and post-treatment visits in order to track patient progress.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: March 23, 2021
• Est. primary completion date: March 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Males or females with MDD receiving treatment at the iKare Mood Trauma Recovery Clinic between the ages of 18-65 years;

2. Meeting the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria for MDD as determined using the Mini-International Psychiatric Interview (MINI)

3. Meeting the Patient Health Questionnaire-9 (PHQ-9 > 14) and/or the Structured Interview Guide for the Montgomery-Ashberg Depression Rating Scale (SIGMA>18) criteria for treatment resistance in MDD despite completing at least one adequate trial of an Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) at an FDA-recommended dose for at least 6-8 weeks.

4. Subjects on SSRIs or other antidepressants, hypnotic medications including modulators of Gamma-Aminobutryic Acid (GABA)-A receptor function, trazodone, atypical neuroleptic or other psychotropic medications such as prazosin may enter the study if they are deemed to be on a stable dose of their medication.

5. Able to provide written informed consent.

6. Able to read and write English.

Exclusion Criteria:

1. Subjects with a diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or currently exhibiting psychotic features as confirmed by MINI.

2. Serious, active suicidal risk as assessed by evaluating psychiatrist. Serious active suicidal risk is determine as imminent risk of suicide reflected in a subject having a plan and intent to end his or her life. History of suicidality in itself is not exclusion for participation in this protocol so long as the evaluating psychiatrist determines that there is an absence of serious active suicidal risk and the means to keep subjects safe.

3. Substance use disorder during the 3 months prior to screening; except for Mild or Moderate Alcohol Use Disorder according to DSM-V criteria.

4. Any history or signs of serious medical or neurological illness including seizure disorders. Except for seizures, a subject with a clinical abnormality may be included only if the study clinician considers the illness will not introduce additional risk and will not interfere with the study procedures.

5. Females will be excluded if they are pregnant (i.e. positive pregnancy test identified after their intake at the treatment clinic).

6. History of traumatic brain injury (TBI) with loss of consciousness for 20 minutes or more as determined by the Brief Traumatic Brain Injury Screen (TBI Screening Tool).

7. Any history or signs of metal objects (e.g. surgical clips, cardiac pacemakers, metal implants, etc.) in the body at the time of screening. MRI can have risks for persons with foreign bodies implanted in their body.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Device:
• repetitive transcranial magnetic stimulation
The MagPro R30 is an advanced, high performance magnetic stimulator designed primarily for non-invasive clinical use. The non-invasive brain stimulation system will be used to deliver repetitive electromagnetic pulses in this research study's treatment of major depressive disorder.
• robotic arm
This robotic system is based on a commercially available neurosurgical robot. The robot is mounted on a mobile (i.e. retractable wheels) cart which holds the robot controller and the TMS power supply and pulse-generation computer. The robotic system will be used for TMS coil positioning/targeting.

Locations

Country	Name	City	State
United States	Ikare, Mood, Trauma, Recovery Clinic	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio	IKARE Mood, Trauma, Recovery Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

O'Reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, McDonald WM, Avery D, Fitzgerald PB, Loo C, Demitrack MA, George MS, Sackeim HA. Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry. 2007 Dec 1;62(11):1208-16. Epub 2007 Jun 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Depression Severity (MADRS)	Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to four weeks (the conclusion of rTMS treatment)
Secondary	Change in Depression Severity (MADRS)	Measured by the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
Secondary	Clinically Significant Response (MADRS)	Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to four weeks (the conclusion of rTMS treatment)
Secondary	Clinically Significant Response (MADRS)	Defined as greater than or equal to a 50% decrease in the Montgomery-Ashberg Depression Rating Scale. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
Secondary	Remission From Depression (MADRS)	Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to four weeks (the conclusion of rTMS treatment)
Secondary	Remission From Depression (MADRS)	Defined as Montgomery-Ashberg Depression Rating Scale score less than or equal to 10. This is a 10-item diagnostic questionnaire with an overall score range from 0 to 60. A higher score indicates more severe depression: 0 to 6 - normal/symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.	Baseline to sixteen weeks (twelve weeks after the conclusion of rTMS treatment)
Secondary	Functional Connectivity Changes of the Targeted Brain Network(s) Following rTMS Treatment	resting-state fMRI scan will also be used to assess, network-specific functional connectivity differences between each subject's pre-treatment and post-treatment scans.; The purpose of the Z score is to "standardize" distributions so that each has a mean of 0, and standard deviation as 1, so we can then make comparisons.; Standard Score, the "Z-Score": A way to make a comparison between values on two different normal curves by converting the values to the number of standard deviations above or below the mean.	Baseline to four weeks (the conclusion of rTMS treatment)