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

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01162382
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arm: 1
• Duration (Months): 44
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Device: Transcranial Magnetic Stimulation	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depressive Disorder: A Functional Connectivity Magnetic Resonance Imaging (fcMRI) Study
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Transcranial Magnetic Stimulation Open-label transcranial magnetic stimulation

Device: Transcranial Magnetic Stimulation; 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.; Other Names: Magstim Rapid stimulator

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale-24 Point Version (HDRS-24) [At study entry and within 2 days of exiting 4 weeks of rTMS treatment]

   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

1. fCMRI Results [At study entry and within 2 days of exiting 4 weeks of rTMS treatment]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Jose Garcia, MD, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Review.
• 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. Review.
• 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.
• 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. Review.
• Zou K, Deng W, Li T, Zhang B, Jiang L, Huang C, Sun X, Sun X. Changes of brain morphometry in first-episode, drug-naïve, 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.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01162382
• Other Study ID Numbers: WUSM3621222-201110079
• First Posted: Jul 14, 2010
• Last Update Posted: Feb 18, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by Washington University School of Medicine: transcranial magnetic stimulation; TMS; rTMS; depression; fcMRI; EEG
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major

Study Results

Participant Flow

Arm/Group Title	Transcranial Magnetic Stimulation
Arm/Group Description	Open-label transcranial magnetic stimulation Transcranial Magnetic Stimulation: 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.
Period Title: Overall Study
STARTED	0
COMPLETED	0
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Transcranial Magnetic Stimulation
Arm/Group Description	Open-label transcranial magnetic stimulation Transcranial Magnetic Stimulation: 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.
Overall Participants	0
Age () []
<=18 years
Between 18 and 65 years
>=65 years
Age () []
Sex: Female, Male () []
Female
Male
Region of Enrollment (participants) []

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

No data are available for this study as the study was terminated and PI has left the institution. Multiple efforts to contact the PI for the relevant data have failed.

Arm/Group Title	Transcranial Magnetic Stimulation
Arm/Group Description	Open-label transcranial magnetic stimulation Transcranial Magnetic Stimulation: 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.
Measure Participants	0

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

No data are available for this study as the study was terminated and PI has left the institution. Multiple efforts to contact the PI for the relevant data have failed.

Arm/Group Title	Transcranial Magnetic Stimulation
Arm/Group Description	Open-label transcranial magnetic stimulation Transcranial Magnetic Stimulation: 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.
Measure Participants	0

Adverse Events

Time Frame	No data are available for this study as the study was terminated and PI has left the institution. Multiple efforts to contact the PI for the relevant data have failed.
Adverse Event Reporting Description	No data are available for this study as the study was terminated and PI has left the institution. Multiple efforts to contact the PI for the relevant data have failed.
Arm/Group Title	Transcranial Magnetic Stimulation
Arm/Group Description	Open-label transcranial magnetic stimulation Transcranial Magnetic Stimulation: 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.
All Cause Mortality
	Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Transcranial Magnetic Stimulation
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

No data are available for this study as the study was terminated and PI has left the institution. Multiple efforts to contact the PI for the relevant data have failed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.