Functional Brain Imaging Study of Response to Repetitive TMS (rTMS) Treatment of Major Depression

NCT01768052 | Unknown

• 1 other identifier: 2012P002394
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators plan to use optical brain imaging technology to observe patients with current major depression before, during, and after repetitive Transcranial Magnetic Stimulation (rTMS) clinical treatment. Clinical treatment involves 20-30 rTMS sessions over the course of 4-6 weeks. Our primary hypotheses are as follows:

1. 1.Primary Hypothesis: In patients with a positive response to rTMS, the investigators will observe an increase in the strength of connectivity as measured by fMRI among brain regions in the cognitive control network after 4 weeks of treatment.
2. 2.Secondary Hypothesis: Brain activation measured by functional Near-Infrared Spectroscopy(fNIRS) in the dorso-lateral prefrontal cortex (DLPFC) during rTMS will increase as the number of treatments increase. Detection of this increase in brain activity at the beginning of the treatment help researchers and physicians assess treatment response.

Conditions

Major Depression

Keywords

MDD, major depression, treatment-resistant

Outcome Measures

Primary Outcomes (1)

• Change in the connectivity strength in the CCN as assessed by fMRI

  •To determine if an increase in the strength of connectivity as measured by fMRI among brain regions in the CCN is observed after 4 weeks of treatment (approximately 20 treatment sessions) in patients with a positive response to rTMS. Participants will undergo fMRI scans prior to beginning TMS treatment (Week 0) and after completing TMS treatment (Weeks 5-7, depending on length of treatment time). Participants will undergo fNIRS monitoring during the TMS treatment sessions (average: Weeks 1-4).

  Participants will be followed for the duration of their TMS treatment and pre- and post-fMRI scans, an expected average of 5-7 weeks

Secondary Outcomes (1)

• Change in brain activation in DLPFC as assessed by fNIRS monitoring

  Participants will be followed for the duration of their TMS treatment, an expected average of 4-6 weeks

Study Arms (1)

functional Near Infrared Spectroscopy

Noninvasive functional Near Infrared Spectroscopy (fNIRS) monitoring will take place during patients' clinical rTMS treatment sessions.

Device: functional Near Infrared Spectroscopy

Interventions

functional Near Infrared Spectroscopy DEVICE

fNIRS monitoring during rTMS treatment sessions.

Also known as: ISS Imagent

functional Near Infrared Spectroscopy

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Male and female participants with major depressive disorder (single or recurrent episode), current episode depressed with current episode duration of three years or less. Of note, subjects are referred by the Transcranial Magnetic Stimulation (TMS) Service at McLean Hospital only.

You may qualify if:

• Subjects must be 21-45 years old.
• Current episode of depression must be of a duration of three years or less
• Participants must have a score of 18 or more on the 24-item version of the HDRS
• Participants must have failed at least one adequate trial of antidepressant medication in this or the most recent depressive episode, but not more than four medications.
• Alternatively, they can have shown an inability to tolerate four such agents due to side effects
• Participants may be medicated or un-medicated.
• Women entering this study must complete a urine pregnancy screen prior to fMRI scanning unless they are post-menopausal, clinically defined as no menses in greater than 12 months or having had surgical removal of the ovaries.
• Subjects must be in inpatient/outpatient treatment with a prescribing mental health clinician.
• Subjects will meet DSM-IV criteria for or Major Depressive Disorder and be currently depressed.
• Subject must have a HAM-D score ≥ 18 and a MADRS score \> 18.
• At the discretion of a study psychiatrist or PI, a HAM-D/MADRS score of less than 18 may be accepted if enough depressive symptoms are present and the subject meets DSM criteria for depression.
• Capable of giving informed consent, including compliance with restrictions and restrictions listed on consent form.

You may not qualify if:

• Currently pregnant or planning to be pregnant during the course of the study, as verified by positive pregnancy test on fMRI scan days, or childbearing potential and not using adequate contraception. Adequate contraception includes birth control pills, birth control shots, or a non-metallic, MRI-compatible intrauterine device (IUD). Those not of childbearing potential include post-menopausal for more than 6 months, surgically sterilized, or male participants.
• Active neurological diseases, history of seizure disorder, dementias, or acute medically unstable or unmanaged physical illnesses.
• Failed more than four antidepressant medications in this or the most recent depressive episode
• Any contraindication to MRI scanning as assessed by pre-screening MRI questionnaire (including, but not limited to, the presence of ferrous implant, pacemaker, etc…).
• History of clinically significant claustrophobia.
• Weight greater than 250 pounds (\>113.4kg).
• Evidence of drug use, nicotine use, alcohol use, or caffeine use by participant and/or clinical observation on the fMRI scanning days.
• Patients who, in the investigators' judgment, will not likely be able to comply with the study protocol.

Sponsors & Collaborators

• Mclean Hospital: lead
• National Alliance for Research on Schizophrenia and Depression: collaborator

Study Sites (2)

McLean Hospital

Belmont, Massachusetts, 02478, United States

RECRUITING

McLean Imaging Center/McLean TMS Service

Belmont, Massachusetts, 02478, United States

RECRUITING

Related Publications (11)

• Hallett M. Transcranial magnetic stimulation: a primer. Neuron. 2007 Jul 19;55(2):187-99. doi: 10.1016/j.neuron.2007.06.026.

  PMID: 17640522 BACKGROUND

• Sheline YI, Price JL, Yan Z, Mintun MA. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11020-5. doi: 10.1073/pnas.1000446107. Epub 2010 Jun 1.

  PMID: 20534464 BACKGROUND

• Veer IM, Beckmann CF, van Tol MJ, Ferrarini L, Milles J, Veltman DJ, Aleman A, van Buchem MA, van der Wee NJ, Rombouts SA. Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Front Syst Neurosci. 2010 Sep 20;4:41. doi: 10.3389/fnsys.2010.00041. eCollection 2010.

  PMID: 20941370 BACKGROUND

• Schlosser RG, Wagner G, Koch K, Dahnke R, Reichenbach JR, Sauer H. Fronto-cingulate effective connectivity in major depression: a study with fMRI and dynamic causal modeling. Neuroimage. 2008 Nov 15;43(3):645-55. doi: 10.1016/j.neuroimage.2008.08.002. Epub 2008 Aug 9.

  PMID: 18761094 BACKGROUND

• Vasic N, Walter H, Sambataro F, Wolf RC. Aberrant functional connectivity of dorsolateral prefrontal and cingulate networks in patients with major depression during working memory processing. Psychol Med. 2009 Jun;39(6):977-87. doi: 10.1017/S0033291708004443. Epub 2008 Oct 10.

  PMID: 18845009 BACKGROUND

• Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, Filippini N, Watkins KE, Toro R, Laird AR, Beckmann CF. Correspondence of the brain's functional architecture during activation and rest. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5. doi: 10.1073/pnas.0905267106. Epub 2009 Jul 20.

  PMID: 19620724 BACKGROUND

• Villringer A, Chance B. Non-invasive optical spectroscopy and imaging of human brain function. Trends Neurosci. 1997 Oct;20(10):435-42. doi: 10.1016/s0166-2236(97)01132-6.

  PMID: 9347608 BACKGROUND

• Hanaoka N, Aoyama Y, Kameyama M, Fukuda M, Mikuni M. Deactivation and activation of left frontal lobe during and after low-frequency repetitive transcranial magnetic stimulation over right prefrontal cortex: a near-infrared spectroscopy study. Neurosci Lett. 2007 Mar 6;414(2):99-104. doi: 10.1016/j.neulet.2006.10.002. Epub 2007 Feb 9.

  PMID: 17293047 BACKGROUND

• Kozel FA, Tian F, Dhamne S, Croarkin PE, McClintock SM, Elliott A, Mapes KS, Husain MM, Liu H. Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity. Neuroimage. 2009 Oct 1;47(4):1177-84. doi: 10.1016/j.neuroimage.2009.05.016. Epub 2009 May 14.

  PMID: 19446635 BACKGROUND

• Tian F, Kozel FA, Yennu A, Croarkin PE, McClintock SM, Mapes KS, Husain MM, Liu H. Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography. J Biomed Opt. 2012 Nov;17(11):116020. doi: 10.1117/1.JBO.17.11.116020.

  PMID: 23139044 BACKGROUND

• Tong Y, Frederick BD. Time lag dependent multimodal processing of concurrent fMRI and near-infrared spectroscopy (NIRS) data suggests a global circulatory origin for low-frequency oscillation signals in human brain. Neuroimage. 2010 Nov 1;53(2):553-64. doi: 10.1016/j.neuroimage.2010.06.049. Epub 2010 Jun 28.

  PMID: 20600975 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Yunjie Tong, PhD

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

• Blaise Frederick, Ph.D.

  Mclean Hospital

  STUDY DIRECTOR

• Oscar Morales, M.D.

  McLean Hospital, Transcranial Magnetic Stimulation (TMS) Service

  STUDY DIRECTOR

Central Study Contacts

Yunjie Tong, PhD

CONTACT

617-855-3620; ytong@mclean.harvard.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 15, 2013
• Study Start: June 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: May 4, 2015

Record last verified: 2015-05

Locations

US (2)