Major Depressive DisorderGPIINCT02307617
Glutamate Probes in Adolescent Depression
An observational study of Major Depressive Disorder and Major Depressive Disorder, Recurrent, run by Mayo Clinic at 1 site in United States.
Trial summary
The purpose of this study is to learn if measures of brain chemicals from a brain scan called Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) and brain activity (known as cortical excitability and inhibition) collected by Transcranial Magnetic Stimulation (TMS) are different in adolescents with depression who… Read more about this study
- Who is it for?
- Ages 13 to 21 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Major Depressive Disorder, Recurrent, Major Depressive Disorder, Remitted
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2014to 17 Apr 2017
- 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
- Healthy volunteers accepted
- 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 \& 4):
- Must have a diagnosis of Major Depressive Disorder (MDD)
- Single episode or recurrent; moderate to severe.
- The MDD diagnosis is based on the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children - Past and Lifetime (K-SADS-PL).
- This semi-structured psychiatric interview will be administered by a psychiatrist, Ph.D. level psychologist, or equivalent professional with extensive clinical experience.
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- Must have a Childhood Depression Rating Scale-Revised (CDRS-R) score of ≥ 40
- Must have a Clinical Global Impression Severity (CGI-S) Scale of ≥ 4
- Group 1: (Healthy Controls; 50 Subjects): Healthy volunteers who are 13-21 years of age with no current or lifetime mental health diagnoses and no current or lifetime psychotropic medication treatment.
- Group 2: (50 subjects): Subjects with moderate to severe MDD for which an SSRI has been clinically indicated.
- If initiating SSRI treatment, medication must be started ± 7 days of the baseline visit
- Subjects and parents in group 2 will be eligible to return in 6-8 weeks for a follow up visit that includes mood assessments and evaluations.
- Subjects who have been adherent to their clinically prescribed medication will be eligible for a second MRI/MRS scan and TMS measures within 7 days of the second visit.
- Subjects who choose not to initiate treatment with an SSRI will have a baseline visit only
- Subjects who discontinue or change their medication after the baseline will not be eligible for a follow-up visit
- Group 3: (50 subjects): Subjects with moderate to severe MDD that has responded to treatment with an SSRI.
- Response will be defined as a 1 (very much) or 2 (much) improved on a CGI-Improvement Scale. This is the current acceptable standard in child and adolescent psychopharmacological research.
- Group 4: (50 subjects): Subjects with moderate to severe MDD that has not responded to treatment with an SSRI as defined above with CGI scale score.
- Subject and parent or guardian (if under age 18) must be capable of providing informed consent
- Subjects and at least 1 parent must be fluent in English. • Subjects 18 years of age or older do not require an English-speaking parent
Who cannot join
- 4.2 Exclusion Criteria For all Subjects:
- Contraindications to MRI/MRS, as determined by the MRI safety screen and MRI safety codes.
- 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 the study only)
- Prior brain surgery.
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- Risk for increased intracranial pressure such as a brain tumor.
- Any unstable medical condition.
- 4.2.1 Exclusion Criteria for Healthy Control Group only:
- Current or past mental health diagnoses in subjects or first degree relatives of subjects.
- Current or past mental health medications.
- 4.2.2 Exclusion Criteria for MDD Groups only:
- Primary Axis I or II disorder other than MDD.
- Unprovoked seizure history, seizure disorder, history of febrile seizures, first degree relative with epilepsy
- Taking medication(s) that lower seizure threshold
- Any significant findings on the TMS adult safety screen (TASS).
- 4.2.3 Exclusion Criteria for Group 2 only:
- 1. Subject has started SSRI medication more than 7 days prior to the baseline visit.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to learn if measures of brain chemicals from a brain scan called Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) and brain activity (known as cortical excitability and inhibition) collected by Transcranial Magnetic Stimulation (TMS) are different in adolescents with depression who are in different stages of treatment.
Researchers are conducting this study to learn more about how the brain works in adolescents with depression and without depression (healthy controls). This is important because it may identify a biological marker (a measure of how bad an illness is) for depression that could one day be used to identify depressed adolescents who would benefit from certain treatments (medications for example) or to monitor how well treatments are working.
Read the detailed description
This is a cross-sectional and longitudinal neurophysiology research study of 200 adolescent subjects in varying stages of major depressive disorder (MDD). The aims of this study are designed to gain an understanding of (1) the role of glutamate in the neurophysiology and pharmacologic treatment of child and adolescent MDD; (2) the role of gamma-aminobutyric acid (GABA) in the neurophysiology and pharmacologic treatment of child and adolescent MDD; (3) the trajectory of glutamatergic and GABAergic functioning in human development with MDD.
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3 Tesla (3T). Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
- Conditions
- Major Depressive Disorder, Major Depressive Disorder, Recurrent, Major Depressive Disorder, Remitted
- Keywords
- Major depressive disorder, MDD, healthy control, selective serotonin reuptake inhibitor, SSRI, depression, transcranial magnetic stimulation, TMS, magnetic resonance spectroscopy, MRS, adolescent, mild MDD, mild depression, cortical excitability, cortical inhibition, cortical silent period, motor threshold, intracortical facilitation, intracortical inhibition, motor cortex
- Medical subject headings
- Depressive Disorder, Major, Recurrence, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 2 | Adolescent participants who plan to start selective serotonin reuptake inhibitor (SSRI) treatment for their depression. Data will be collected prior to the start of the medication and again 6 weeks after the start of the medication. | |
| Medication Responders | Adolescent participants who have responded to SSRI treatment for their depression. | |
| Medication Non-Responders | Adolescent participants with depression that has not responded to SSRI treatment. | |
| Healthy Controls | Adolescent participants who have no current or past mental health diagnoses. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentrations of GABA and glutamate in the brains of adolescents with MDD.
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
Measured: Baseline
The change of GABA and glutamate concentrations in adolescents with MDD after 6 weeks of SSRI treatment.
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
Measured: Baseline to 6 weeks (group 2)
Secondary outcomes (2)
The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD
Glutamatergic and GABAergic function will be measured using single and paired-pulse Transcranial Magnetic Stimulation (TMS) measures of cortical excitability (motor threshold and intracortical facilitation) and inhibition (cortical silent period and intracortical inhibition).
Measured: Baseline
The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD after 6 weeks of SSRI treatment.
Glutamatergic and GABAergic function will be measured using single and paired-pulse Transcranial Magnetic Stimulation (TMS) measures of cortical excitability (motor threshold and intracortical facilitation) and inhibition (cortical silent period and intracortical inhibition).
Measured: Baseline to 6 weeks (group 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2014 (estimated)
- Study start1 Aug 2014
- Primary completion17 Apr 2017
- Study completion17 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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
- Other
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- 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
- NCT02307617
- Sponsor's protocol ID
- 14-004662
- Acronym
- GPII
- Status last verified
- Apr 2021
- First submitted
- 8 Sep 2014
- Last updated
- 23 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamate Probes in Adolescent Depression
- ClinicalTrials.gov ID
- NCT02307617
- Acronym / sponsor ID
- GPII / 14-004662
- Conditions
- Major Depressive Disorder, Major Depressive Disorder, Recurrent, Major Depressive Disorder, Remitted
- Keywords
- Major depressive disorder, MDD, healthy control, selective serotonin reuptake inhibitor, SSRI, depression, transcranial magnetic stimulation, TMS
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 1 Aug 2014 (actual)
- Primary completion
- 17 Apr 2017 (actual)
- Study completion
- 17 Apr 2017 (actual)
- First posted
- 4 Dec 2014 (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 chemicals from a brain scan called Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) and brain activity (known as cortical excitability and inhibition) collected by Transcranial Magnetic Stimulation (TMS) are different in adolescents with depression who are in different stages of treatment.
Researchers are conducting this study to learn more about how the brain works in adolescents with depression and without depression (healthy controls). This is important because it may identify a biological marker (a measure of how bad an illness is) for depression that could one day be used to identify depressed adolescents who would benefit from certain treatments (medications for example) or to monitor how well treatments are working.
Detailed description
This is a cross-sectional and longitudinal neurophysiology research study of 200 adolescent subjects in varying stages of major depressive disorder (MDD). The aims of this study are designed to gain an understanding of (1) the role of glutamate in the neurophysiology and pharmacologic treatment of child and adolescent MDD; (2) the role of gamma-aminobutyric acid (GABA) in the neurophysiology and pharmacologic treatment of child and adolescent MDD; (3) the trajectory of glutamatergic and GABAergic functioning in human development with MDD.
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3 Tesla (3T). Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
Study design
- Observational model
- Case-control
- Time perspective
- Other
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 2 | – | –Adolescent participants who plan to start selective serotonin reuptake inhibitor (SSRI) treatment for their depression. Data will be collected prior to the start of the medication and again 6 weeks after the start of the medication. |
| Medication Responders | – | –Adolescent participants who have responded to SSRI treatment for their depression. |
| Medication Non-Responders | – | –Adolescent participants with depression that has not responded to SSRI treatment. |
| Healthy Controls | – | –Adolescent participants who have no current or past mental health diagnoses. |
Who may qualify
- Ages
- 13 to 21 years
- Sex
- All
- Healthy volunteers
- 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 (20 listed)
- Adolescents from the ages of 13 to 21, male or female.
- Subjects with MDD (Groups 2, 3 \& 4):
- Group 1: (Healthy Controls; 50 Subjects): Healthy volunteers who are 13-21 years of age with no current or lifetime mental health diagnoses and no current or lifetime psychotropic medication treatment.
- Group 2: (50 subjects): Subjects with moderate to severe MDD for which an SSRI has been clinically indicated.
- Group 3: (50 subjects): Subjects with moderate to severe MDD that has responded to treatment with an SSRI.
Key exclusion criteria (18 listed)
- Contraindications to MRI/MRS, as determined by the MRI safety screen and MRI safety codes.
- 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 the study only)
- Prior brain surgery.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Concentrations of GABA and glutamate in the brains of adolescents with MDD.
Time frame: Baseline
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
The change of GABA and glutamate concentrations in adolescents with MDD after 6 weeks of SSRI treatment.
Time frame: Baseline to 6 weeks (group 2)
Glutamate concentrations in the anterior cingulate cortex (ACC) and left dorsolateral prefrontal (L-DLPFC) cortex will be evaluated using proton magnetic resonance spectroscopy (MRS) at 3T. Glutamatergic cortical excitability measures (with motor threshold and intracortical facilitation paradigms), and GABAergic cortical inhibitory measures (with cortical silent period and intracortical inhibition paradigms) will be studied using single and paired-pulse transcranial magnetic stimulation (TMS) paradigms.
2 secondary outcomes
The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD
Time frame: Baseline
The effect of glutamatergic and GABAergic functioning on human development in adolescents with MDD after 6 weeks of SSRI treatment.
Time frame: Baseline to 6 weeks (group 2)
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 23 Apr 2021.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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 and Major Depressive Disorder, Recurrent, 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 20 inclusion and 18 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 23 Apr 2021. 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?
Concentrations of GABA and glutamate in the brains of adolescents with MDD. (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Apr 2021.