Major Depressive Disorder, Recurrent, MildNCT01718730
Cortical Excitability and Inhibition in MDD
An observational study of Major Depressive Disorder, Recurrent, Mild and Depressive Disorder, Major, run by Mayo Clinic at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 13 to 21 years
- Conditions the study is for
- Major Depressive Disorder, Recurrent, Mild, Depressive Disorder, Major
- What is being tested?
- Transcranial Magnetic Stimulation (TMS) and Magnetic Resonance Spectroscopy and Imaging
- Type of treatment
- Medical device
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Aug 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
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.
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder
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.
Read the 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).
- Being tested
- Transcranial Magnetic Stimulation (TMS), Magnetic Resonance Spectroscopy and Imaging
- Keywords
- 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
- Medical subject headings
- Depressive Disorder, Major, Recurrence, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Magnetic Stimulation (TMS)Device
Also called Device: Magstim Model 200
Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition.
Magnetic Resonance Spectroscopy and ImagingDevice
Also called MRS/MRI
MRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex.
| Study group | Role | What they receive |
|---|---|---|
| Mild depression | Subjects with mild, but clinically significant depression Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Magnetic Resonance Spectroscopy and Imaging | |
| Moderate to Severe MDD | Subjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Magnetic Resonance Spectroscopy and Imaging | |
| MDD with response to SSRI | Subjects with moderate to severe major depressive disorder that has responded to an SSRI Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Magnetic Resonance Spectroscopy and Imaging | |
| MDD without response to SSRI | Subjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI Receives: Device: Transcranial Magnetic Stimulation (TMS); Device: Magnetic Resonance Spectroscopy and Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cortical Excitability and Inhibition at Motor Cortex
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.
Measured: Baseline
Secondary outcomes (1)
Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex
Glutamate concentrations will be measured with proton magnetic resonance imaging at 3T.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionAug 2019
- Study completionAug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive Disorder, Recurrent, MildStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Neuronetics
- Responsible party
- Principal investigator, Paul E. Croarkin, Mayo Clinic
- Investigators
- Paul E Croarkin, D.O., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01718730
- Sponsor's protocol ID
- 12-000335
- Status last verified
- Oct 2019
- First submitted
- 29 Oct 2012
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Croarkin PE, Nakonezny PA, Husain MM, Port JD, Melton T, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. Brain Stimul. 2014 Mar-Apr;7(2):243-51. doi: 10.1016/j.brs.2013.11.006. Epub 2013 Dec 3.
PubMed 24360599
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cortical Excitability and Inhibition in Children and Adolescents With Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT01718730
- Acronym / sponsor ID
- 12-000335
- Keywords
- TMS, Adolescent, Child, MDD, Major depressive disorder, Mild MDD, Mild depression, SSRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- Neuronetics
- Study start
- Oct 2012
- Primary completion
- Aug 2019 (actual)
- Study completion
- Aug 2019 (actual)
- First posted
- 31 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Mild depression | – | Device: Transcranial Magnetic Stimulation (TMS), Device: Magnetic Resonance Spectroscopy and ImagingSubjects with mild, but clinically significant depression |
| Moderate to Severe MDD | – | Device: Transcranial Magnetic Stimulation (TMS), Device: Magnetic Resonance Spectroscopy and ImagingSubjects with moderate to severe major depressive disorder who have not yet initiated treatment with an SSRI |
| MDD with response to SSRI | – | Device: Transcranial Magnetic Stimulation (TMS), Device: Magnetic Resonance Spectroscopy and ImagingSubjects with moderate to severe major depressive disorder that has responded to an SSRI |
| MDD without response to SSRI | – | Device: Transcranial Magnetic Stimulation (TMS), Device: Magnetic Resonance Spectroscopy and ImagingSubjects with moderate to severe major depressive disorder which has not responded to treatment with an SSRI |
Who may qualify
- Ages
- 13 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- 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.
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Magnetic Stimulation (TMS)Also: Device: Magstim Model 200Single and paired-pulse TMS applied to the motor cortex will collect measures of cortical excitability and inhibition. | Device | MDD with response to SSRI, MDD without response to SSRI, Mild depression, Moderate to Severe MDD |
| Magnetic Resonance Spectroscopy and ImagingAlso: MRS/MRIMRS/MRI Scans will examine glutamate concentrations in the motor cortex and anterior cingulate cortex. | Device | MDD with response to SSRI, MDD without response to SSRI, Mild depression, Moderate to Severe MDD |
Primary outcome
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.
1 secondary outcome
Glutamate Concentrations in the Motor Cortex and Anterior Cingulate Cortex
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Derived from this study: PubMed 24360599Croarkin PE, Nakonezny PA, Husain MM, Port JD, Melton T, Kennard BD, Emslie GJ, Kozel FA, Daskalakis ZJ. Evidence for pretreatment LICI deficits among depressed children and adolescents with nonresponse to fluoxetine. Brain Stimul. 2014 Mar-Apr;7(2):243-51. doi: 10.1016/j.brs.2013.11.006. Epub 2013 Dec 3.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Major Depressive Disorder, Recurrent, Mild
Recruiting
Mindfulness-Based Cognitive Therapy (MBCT) for the Prevention of Depression Relapse or Recurrence Using Videoconference
Major Depressive Disorder, Recurrent, in Remission, Major Depressive Disorder, Recurrent, Mild
Active, not recruiting
Prevention of Alzheimer's Disease With CR Plus tDCS in Mild Cognitive Impairment and Depression (PACt-MD)
Mild Cognitive Impairment, Major Depressive Disorder, Recurrent, In Remission
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul E Croarkin, D.O. principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depressive Disorder, Recurrent, Mild and Depressive Disorder, Major, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cortical Excitability and Inhibition at Motor Cortex (time frame: Baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01718730, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.