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Repetitive Transcranial Magnetic Stimulation for Treating Depression: A Functional Magnetic Resonance Imaging Study

Primary Purpose

Major Depressive Disorder

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Transcranial Magnetic Stimulation

About this trial

This is an interventional basic science trial for Major Depressive Disorder focused on measuring transcranial magnetic stimulation, TMS, rTMS, depression, fcMRI, EEG

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

SCREENING/DIAGNOSTIC REQUIREMENTS:

Male or female outpatients, ages 18-50 (some literature has shown increasing cortical distance with age that may affect treatment outcome
Hamilton Rating Scale of Depression (HRSD-24) > 18
New onset major depression or untreated recurrent major depression per DSM-IV-TR38 criteria.
Not taking antidepressant medication or any other psychotropic medication
Using an adequate contraceptive method
Able to give informed consent
Available for 4 weeks of daily therapy, working hours, Mon.-Fri.
English-speaking

Exclusion Criteria:

DIAGNOSTIC EXCLUSIONS:

Co-morbid psychiatric diagnosis of bipolar disorder, acute OCD, schizophrenia or schizoaffective or concurrent treatment with outpatient ECT, or personality disorder or MDD with suicidal ideation as determined by history and/or by P.I. examination requiring hospital admission or referral for acute care.
Previous failure to respond to treatment with rTMS
Failure to achieve satisfactory improvement in depression after two or more adequate trials of antidepressant medications.

MEDICAL EXCLUSIONS:

Patients newly diagnosed with thyroid dysfunction
History of drug and/or ETOH dependence
History of seizures
History of head injury with loss of consciousness > 5 minutes
Any implantable metal object in the skull or near their head
Any implantable devices such as a cardiac pacemaker, vagal nerve stimulator, etc.
Positive urine pregnancy test
Severe migraine headaches uncontrolled with routine non-narcotic medication
Any medical condition in the opinion of the Investigator that might confound the results of the study Contraindications to fcMRI procedure
Intake of NSAIDS, narcotic or muscle relaxants within 72 hours of the fMRI protocol.
Claustrophobia.
Left-handedness (may influence cerebral cortical hemispheric dominance).
Inability to tolerate, or medical contraindication to MRI testing (e.g. metal prostheses or implants, history of claustrophobia)

PROTOCOL SPECIFIC EXCLUSIONS:

Unable to determine motor threshold for determining treatment dose with rTMS device
Mini Mental Status Exam (MMSE)70 score < 24.

Sites / Locations

Washington University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transcranial Magnetic Stimulation

Arm Description

Open-label transcranial magnetic stimulation

Outcomes

Primary Outcome Measures

Hamilton Depression Rating Scale-24 Point Version (HDRS-24)

HDRS-24 will be used to measure response to rTMS treatment. A 50% decrease in HDRS-24 score will indicate treatment response; HDRS-24 < 10 will indicate remission.

Secondary Outcome Measures

fCMRI Results

Imaging studies will be compared to determine if any changes in functional connectivity can be correlated with treatment response.

Full Information

NCT ID

NCT01162382

First Posted

November 30, 2009

Last Updated

February 8, 2019

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01162382

Brief Title

Repetitive Transcranial Magnetic Stimulation for Treating Depression: A Functional Magnetic Resonance Imaging Study

Official Title

Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depressive Disorder: A Functional Connectivity Magnetic Resonance Imaging (fcMRI) Study

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Terminated

Why Stopped

Grant support ended following which the key personnel (PI) left the institution.

Study Start Date

January 2010 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This protocol, "Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depressive Disorder (MDD): A Functional Connectivity Magnetic Resonance Imaging (fcMRI) Study," is an open-label pilot treatment study. The purpose of the present protocol is to treat participants with a diagnosis of Major Depressive Disorder with 4 weeks of rTMS, performing fcMRI and EEG studies prior to and following treatment to determine if treatment response is related to changes in fcMRI and/or EEG results. The investigators hypothesize that patients who respond to treatment will display changes in functional connectivity patterns thought to be related to the occurrence of depressive symptoms.

Detailed Description

Depression is accompanied by rumination that supports inwardly focused cognitive attention on negative events and emotions. There is evidence to indicate that one aspect of this ruminative behavior lies in an abnormal increase in intra-regional connectivity among elements of the default mode network (DMN). It is also widely recognized that depression is associated with disturbances of cognition that include deficits in attentional processing, including both reductions in processing speed and deficits in selective attentional processing that are considered a part of executive function. Thus, there is at least equal reason to believe that attention and executive control networks might show changes in intra-regional functional connectivity. Given the attentional deficits associated with MDD, we hypothesize that there will be a weakening of intra-network resting state BOLD functional connectivity (rs-fcMRI) in addition to the strengthened connectivity reported by others.Further, we suggest that these shifts in intra-regional connectivity extend to the well-recognized anti-correlated activity between these two networks and support the intrusion of introspective, ruminative thought on cognitive activities that require externally directed attention. To test this hypothesis, we will use fMRI resting state functional connectivity to examine shifts in network connectivity prior to and following rTMS treatment for depression.

6. Conditions and Keywords

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

Major Depressive Disorder

Keywords

transcranial magnetic stimulation, TMS, rTMS, depression, fcMRI, EEG

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

4 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Transcranial Magnetic Stimulation

Arm Type

Experimental

Arm Description

Open-label transcranial magnetic stimulation

Intervention Type

Device

Intervention Name(s)

Transcranial Magnetic Stimulation

Other Intervention Name(s)

Magstim Rapid stimulator

Intervention Description

Four 100-second trains and then one 65-second train, with 30-second inter-train intervals, at 1 Hz and 120% of the resting motor threshold will be applied over the right dorsolateral prefrontal cortex. Subsequently, twenty-five 30-second trains, with a 30-second inter-train interval, at 10 Hz and 120% of the resting motor threshold will be applied over the left dorsolateral prefrontal cortex.

Primary Outcome Measure Information:

Title

Hamilton Depression Rating Scale-24 Point Version (HDRS-24)

Description

HDRS-24 will be used to measure response to rTMS treatment. A 50% decrease in HDRS-24 score will indicate treatment response; HDRS-24 < 10 will indicate remission.

Time Frame

At study entry and within 2 days of exiting 4 weeks of rTMS treatment

Secondary Outcome Measure Information:

Title

fCMRI Results

Description

Imaging studies will be compared to determine if any changes in functional connectivity can be correlated with treatment response.

Time Frame

At study entry and within 2 days of exiting 4 weeks of rTMS treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: SCREENING/DIAGNOSTIC REQUIREMENTS: Male or female outpatients, ages 18-50 (some literature has shown increasing cortical distance with age that may affect treatment outcome Hamilton Rating Scale of Depression (HRSD-24) > 18 New onset major depression or untreated recurrent major depression per DSM-IV-TR38 criteria. Not taking antidepressant medication or any other psychotropic medication Using an adequate contraceptive method Able to give informed consent Available for 4 weeks of daily therapy, working hours, Mon.-Fri. English-speaking Exclusion Criteria: DIAGNOSTIC EXCLUSIONS: Co-morbid psychiatric diagnosis of bipolar disorder, acute OCD, schizophrenia or schizoaffective or concurrent treatment with outpatient ECT, or personality disorder or MDD with suicidal ideation as determined by history and/or by P.I. examination requiring hospital admission or referral for acute care. Previous failure to respond to treatment with rTMS Failure to achieve satisfactory improvement in depression after two or more adequate trials of antidepressant medications. MEDICAL EXCLUSIONS: Patients newly diagnosed with thyroid dysfunction History of drug and/or ETOH dependence History of seizures History of head injury with loss of consciousness > 5 minutes Any implantable metal object in the skull or near their head Any implantable devices such as a cardiac pacemaker, vagal nerve stimulator, etc. Positive urine pregnancy test Severe migraine headaches uncontrolled with routine non-narcotic medication Any medical condition in the opinion of the Investigator that might confound the results of the study Contraindications to fcMRI procedure Intake of NSAIDS, narcotic or muscle relaxants within 72 hours of the fMRI protocol. Claustrophobia. Left-handedness (may influence cerebral cortical hemispheric dominance). Inability to tolerate, or medical contraindication to MRI testing (e.g. metal prostheses or implants, history of claustrophobia) PROTOCOL SPECIFIC EXCLUSIONS: Unable to determine motor threshold for determining treatment dose with rTMS device Mini Mental Status Exam (MMSE)70 score < 24.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jose Garcia, MD

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

19629020

Citation

Demitrack MA, Thase ME. Clinical significance of transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant depression: synthesis of recent data. Psychopharmacol Bull. 2009;42(2):5-38.

Results Reference

background

PubMed Identifier

18824195

Citation

Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJ. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev. 2009 Mar;33(3):279-96. doi: 10.1016/j.neubiorev.2008.09.002. Epub 2008 Sep 9.

Results Reference

background

PubMed Identifier

17573044

Citation

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. doi: 10.1016/j.biopsych.2007.01.018. Epub 2007 Jun 14.

Results Reference

background

PubMed Identifier

19358877

Citation

Savitz JB, Drevets WC. Imaging phenotypes of major depressive disorder: genetic correlates. Neuroscience. 2009 Nov 24;164(1):300-30. doi: 10.1016/j.neuroscience.2009.03.082. Epub 2009 Apr 7.

Results Reference

background

PubMed Identifier

19897176

Citation

Zou K, Deng W, Li T, Zhang B, Jiang L, Huang C, Sun X, Sun X. Changes of brain morphometry in first-episode, drug-naive, non-late-life adult patients with major depression: an optimized voxel-based morphometry study. Biol Psychiatry. 2010 Jan 15;67(2):186-8. doi: 10.1016/j.biopsych.2009.09.014.

Results Reference

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Repetitive Transcranial Magnetic Stimulation for Treating Depression: A Functional Magnetic Resonance Imaging Study

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