We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Cortical Excitability and Inhibition in MDD

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01718730
Recruitment Status : Recruiting
First Posted : October 31, 2012
Last Update Posted : October 19, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

Study Description
Brief Summary:

The purpose of this study is to learn if measures of brain activity are different in children and adolescents with depression who are in different stages of treatment. This is important because it may identify a biological marker for depression that could one day be used to identify depressed children who would benefit from certain treatments (medications for example), or to monitor how well treatments are working. Brain activity measures(known as cortical excitability and inhibition) will be collected by Transcranial Magnetic Stimulation (TMS). TMS is a noninvasive (no surgery or implants) brain stimulation technology which can make parts of the brain work without putting any wires or chemicals into the body. Measurements will take place over one 3-hour visit. This study does not provide any form of treatment.

*There is an optional portion of the study that uses a brain scan to gather measures of brain structure and brain chemicals. The brain scan is called magnetic resonance and spectroscopy (MRI/MRS). MRI/MRS uses magnetic fields to study the structure of the brain and brain chemicals. The PI will determine eligibility for the MRI/MRS portion of the study.


Condition or disease Intervention/treatment
Major Depressive Disorder, Recurrent, Mild Depressive Disorder, Major Device: Transcranial Magnetic Stimulation (TMS) Device: Magnetic Resonance Spectroscopy and Imaging

Detailed Description:

This study is focused on understanding the neurophysiology of major depressive disorder (MDD), and the impact of selective serotonin reuptake inhibitors (SSRIs) in children and adolescents. This is a cross-sectional study which will utilize single and paired-pulse transcranial magnetic stimulation (TMS) to collect measures of glutamatergic cortical excitability (the motor threshold and intracortical facilitation), and GABAergic cortical inhibition (the cortical silent period and intracortical inhibition) of the motor cortex in chilren and adolescents in various disease states of MDD. The optional proton magnetic resonance spectroscopy and imaging scans (MRS/MRI) at 3 Tesla (3T) will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.

This is a biomarker study (MRI/MRS and TMS neurophysiology measures); treatment is not provided in any form. This study will not utilize Repetitive Transcranial Magnetic Stimulation (rTMS).


Study Design

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder
Study Start Date : October 2012
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2018
Groups and Cohorts

Group/Cohort Intervention/treatment
Mild depression
Subjects with mild, but clinically significant depression
Device: Transcranial Magnetic Stimulation (TMS)
Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
Other Name: Device: Magstim Model 200
Device: Magnetic Resonance Spectroscopy and Imaging
MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
Other Name: MRS/MRI
Moderate to Severe MDD
Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI
Device: Transcranial Magnetic Stimulation (TMS)
Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
Other Name: Device: Magstim Model 200
Device: Magnetic Resonance Spectroscopy and Imaging
MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
Other Name: MRS/MRI
MDD with response to SSRI
Subjects with moderate to severe major depressive disorder that has responded to an SSRI
Device: Transcranial Magnetic Stimulation (TMS)
Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
Other Name: Device: Magstim Model 200
Device: Magnetic Resonance Spectroscopy and Imaging
MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
Other Name: MRS/MRI
MDD without response to SSRI
Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI
Device: Transcranial Magnetic Stimulation (TMS)
Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
Other Name: Device: Magstim Model 200
Device: Magnetic Resonance Spectroscopy and Imaging
MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
Other Name: MRS/MRI


Outcome Measures

Primary Outcome Measures :
  1. Cortical Excitability and Inhibition at Motor Cortex [ Time Frame: Baseline ]
    Motor Threshold (MT) is a single-pulse TMS measure of cortical excitability. A higher MT indicates decreased cortical excitability. Intracortical Facilitation (ICF) is a paired-pulse TMS measure of cortical excitability. A higher ICF indicates increased cortical excitability. Cortical Silent Period (CSP) is a single-pulse TMS measure of cortical inhibition. Longer CSP durations indicate greater cortical inhibition. Intracortical Inhibition (ICI) is a paired pulse TMS measure of cortical inhibition. A lower ICI indicates increased cortical inhibition, and a higher ICI indicates decreased cortical inhibition.


Secondary Outcome Measures :
  1. Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex [ Time Frame: Baseline ]
    Glutamate concentrations will be measured with proton magnetic resonance imaging at 3T.


Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   13 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This protocol will plan to screen depressed children and adolescents who are seeking treatment at Mayo Clinic in Rochester, MN, using strict inclusion and exclusion criteria. These adolescents will represent gender and minority distribution consistent with the Rochester metro/rural area demographic distribution. This study will be inclusive of all races, genders, and socioeconomic classes.
Criteria

Inclusion Criteria:

  • Adolescents from the ages of 13 to 21, male or female.
  • Subjects with MDD (groups 2, 3, and 4):
  • Must have a Children's Depression Rating Scale, Revised (CDRS-R) score of 40 or higher
  • Must have a Clinical Global Impression-Severity scale (CGI-S) score of 4 or higher.
  • Group 1: (50 subjects): Subjects who have mild (CDRS-R score < 40) but clinically significant depression.
  • Group 2: (50 subjects): Subjects with moderate to severe MDD who have not yet initiated treatment with an SSRI.
  • Group 3: (50 subjects): Subjects with moderate to severe MDD that has responded to treatment with an SSRI.
  • Group 4: (50 subjects): Subjects with moderate to severe MDD which has not responded to treatment with an SSRI.
  • Capable of providing informed assent (consent if age 18) in addition to consent by parent or guardian.
  • Subjects and at least 1 parent must be fluent in English.

Exclusion Criteria:

  • Primary Axis I or II disorder other than MDD.
  • Unprovoked seizure history, seizure disorder, history of febrile seizures, family history of epilepsy.
  • Any significant findings on the TMS Adult Safety Screen (TASS) or contraindications to MRI/MRS
  • Subjects who are judged by the Principal Investigator to be at imminent risk for self harm or suicide as indicated by interview or C-SSRS.
  • Pregnancy or suspected pregnancy in females.
  • Metal in the head (except the mouth*), implanted medication pumps, cardiac pacemaker.

    * Subjects with braces will be excluded from MRI/MRS portion of study only

  • Prior brain surgery.
  • Risk for increased intracranial pressure such as a brain tumor.
  • Any unstable medical condition.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01718730


Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Katrina Schaefer    507-255-5452    schaefer.katrina@mayo.edu   
Contact: Paul Croarkin, D.O.    507-255-7164      
Principal Investigator: Paul E Croarkin, D.O.         
Sponsors and Collaborators
Mayo Clinic
Neuronetics
Investigators
Principal Investigator: Paul E Croarkin, D.O. Mayo Clinic
More Information

Responsible Party: Paul E. Croarkin, PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01718730     History of Changes
Other Study ID Numbers: 12-000335
First Posted: October 31, 2012    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Paul E. Croarkin, Mayo Clinic:
TMS
Adolescent
Child
MDD
Major depressive disorder
Mild MDD
Mild depression
SSRI
Motor cortex
Cortical excitability
Cortical inhibition
Cortical silent period
Motor threshold
Intracortical facilitation
Intracortical inhibition
gamma-aminobutyric acid (GABA)
Glutamate
N-methyl-D-aspartate (NMDA)
Magnetic resonance spectroscopy
MRS

Additional relevant MeSH terms:
Disease
Depressive Disorder
Depression
Depressive Disorder, Major
Recurrence
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Disease Attributes