Cortical Excitability and Inhibition in MDD

Completed

• Conditions: Major Depressive Disorder, Recurrent, Mild; Depressive Disorder, Major
• Interventions: Device: Transcranial Magnetic Stimulation (TMS); Device: Magnetic Resonance Spectroscopy and Imaging

• Registration Number: NCT01718730
• Lead Sponsor: Mayo Clinic

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.

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 Timeline

• Study Start: 2012-10
• Study First Submitted: 2012-10-29
• Study First Submitted QC: 2012-10-29
• Study First Posted: 2012-10-31
• Primary Completion: 2019-08
• Study Completion: 2019-08
• Status Verified: 2019-10
• Last Update Submitted: 2019-10-20
• Last Update Posted: 2019-10-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

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.

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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.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Mild depression	Transcranial Magnetic Stimulation (TMS)	Subjects with mild, but clinically significant depression
MDD without response to SSRI	Transcranial Magnetic Stimulation (TMS)	Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI
Mild depression	Magnetic Resonance Spectroscopy and Imaging	Subjects with mild, but clinically significant depression
Moderate to Severe MDD	Magnetic Resonance Spectroscopy and Imaging	Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI
MDD with response to SSRI	Magnetic Resonance Spectroscopy and Imaging	Subjects with moderate to severe major depressive disorder that has responded to an SSRI
MDD with response to SSRI	Transcranial Magnetic Stimulation (TMS)	Subjects with moderate to severe major depressive disorder that has responded to an SSRI
MDD without response to SSRI	Magnetic Resonance Spectroscopy and Imaging	Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI
Moderate to Severe MDD	Transcranial Magnetic Stimulation (TMS)	Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI

Primary Outcome Measures

Name	Time	Method
Cortical Excitability and Inhibition at Motor Cortex	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

Name	Time	Method
Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex	Baseline	Glutamate concentrations will be measured with proton magnetic resonance imaging at 3T.

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States