Major Depressive DisorderNCT02727972
Examination of Glutamate and mGluR5 in Psychiatric Disorders
An observational study of Major Depressive Disorder and Post-Traumatic Stress Disorder, run by Yale University at 1 site in United States.
Trial summary
This research study is designed to look at the involvement of the glutamate system in depression. Each subject will undergo a screening appointment to determine study eligibility. Thereafter, the study will take 2 or 3 visits depending on schedule availability and will consist of one MRI scan, and PET scan. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder, Post-Traumatic Stress Disorder, Bipolar Disorder
- What is being tested?
- Cognitive Testing, MRI and PET
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- How many people
- 180 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2012to 13 Jan 2022
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- General inclusion criteria:
- Subjects will be between the ages of 18-70 years old
- English speaking
- No other DSM-5 diagnosis present, besides required as below
- Clinical diagnosis of a current depressive episode
- Medication-free for at least 2 weeks or medicated with a permissible medication
Show all 9Show fewer
- Clinical diagnosis of current PTSD as per DSM-5
- Medication free for at least 2 weeks or medicated with a permissible medication
- No current, or history of, any DSM-5 diagnosis
Who cannot join
- Have a current or past significant medical, neurological or metabolic disorder or head injury that lead to significant long term decline in cognitive abilities as seen by decline in grades or work performance
- Have significant medical illness such that would contraindicate study participation based on above criteria and PI/MD history review
- Have active, significant suicidal ideation
- Have implanted metallic devices or any MR contraindications
- Are women who are pregnant or breastfeeding
- Met DSM-5 criteria for mild substance use disorder (except nicotine and marijuana) within the past 6 months or met DSM-5 criteria for moderate to severe substance use disorder (except nicotine and marijuana) within the past year
Show all 9Show fewer
- Have history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year
- Have given a blood donation within eight weeks of the start of the study
- Have history of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
Trial locations and contacts
1 site in 1 country.
About this study
This research study is designed to look at the involvement of the glutamate system in depression. Each subject will undergo a screening appointment to determine study eligibility. Thereafter, the study will take 2 or 3 visits depending on schedule availability and will consist of one MRI scan, and PET scan. Subjects will also participate in cognitive testing. Depending on camera time, staff availability and subject schedule, total study participation may last 1-2 months.
Read the detailed description
With the recent advancements in positron emission tomography (PET) and radioligand development, the investigators are now able to image and quantify the metabotropic glutamatergic system (mGluR5) in vivo in human subjects. The study proposes a novel investigation of mGluR5 in depression to obtain critical data to advance understanding of the etiology of depression and its associated symptoms of cognitive dysfunction.
Aim 1: To determine mGluR5 availability in individuals with mood disorders compared to healthy controls as measured with PET brain imaging.
Hypothesis 1: The study hypothesizes a decrease in mGluR5 availability in individuals with mood disorders in regions responsible for emotional and cognitive processes, including the amygdala, hippocampus, thalamus, anterior cingulate, and frontal cortices.
Aim 2: To determine if glutamate cycling in individuals with mood disorders is altered as compared to healthy controls as measured with [1H]MRS and [13C]MRS.
Hypothesis 2: The study hypothesizes an increase in glutamate number in individuals with mood disorders as compared to controls.
Aim 3: To determine if the PET alterations in the glutamatergic system of depressed individuals are associated with cognitive deficits observed in depression, including concentration, attention, memory, distractibility, and startle.
Hypothesis 3: The study hypothesizes a positive relationship between mGluR5 availability and cognitive functioning, such that individuals with higher receptor availability will perform better on tests of concentration, attention, memory, distractibility, and startle than individuals with lower receptor availability.
Aim 4: To determine mGluR5 availability in individuals with anxiety and schizophrenia compared to healthy controls as measured with PET brain imaging.
Hypothesis 4: Anxiety disorders such as obsessive compulsive disorder, and delusional disorders such as schizophrenia are frequently comorbid with mood disorders, and the glutamatergic system has been observed to be compromised in these individuals as well. This study will examine if there are regional differences in mGluR5 availability between individuals with depression, bipolar disorder, obsessive compulsive disorder, and schizophrenia.
Aim 5: To examine whether changes in mGluR5 availability are dependent on state, or whether the lower availability is due to trait.
Hypothesis 5: Due to changes in endogenous GLU shown with MRS studies, this study hypothesizes normalization (or increase) in mGluR5 availability in euthymia as compared to depressed state.
- Being tested
- Cognitive Testing, MRI, PET
- Keywords
- depression, bipolar, post-traumatic stress disorder, mood disorders, PET, mGluRr, glutamate system, MRI
- Medical subject headings
- Depressive Disorder, Major, Stress Disorders, Post-Traumatic, Bipolar Disorder, Depression, Mood Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive TestingBehavioural
Verbal assessments as well as computer testing.
MRIOther
Also called Magnetic Resonance Imaging
Anatomical MRIs will be performed on a Siemens 3T Trio at Yale. MR acquisition will be a Sag 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence with 3.34 ms echo time, 2,500 ms repetition time, 1,000 ms inversion time, 7 degree flip angle, and 180 Hz/pixel bandwidth. The image dimensions will be 256 x 256 x 176 and pixel size 0.98 x 0.98 x 1.0 mm. Resting state MRIs will also be obtained as follows: We will be doing 2 six minute scans with subjects in the scanner, eyes open, fixating a cross. TR = 3 secs 45 slices x 3 mm slice thickness = 13.5 cm. In plane resolution = 3 x 3 mm, slice acquisition order = ascending.
PETRadiation
Also called Positron Emission Tomography
High Resolution Research Tomograph (HRRT), the highest resolution human brain scanner available, or HR+ will be used to image subjects. Vital signs (blood pressure, pulse, respiration) will be obtained before and after radiotracer administration. An antecubital venous catheter will be used for IV administration of the radiotracer and for venous blood sampling. A radial artery catheter will be inserted by an experienced physician before the PET scan. At the beginning of each scan, the subject's head will be immobilized and a 6 minute transmission scan using an orbiting 137Cs (HRRT) or 68GE (HR+) point-source is obtained and used for attenuation correction. PET scans will be acquired using bolus or bolus plus constant infusion administration of FPEB or ABP688.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Testing | Cognitive assessments Receives: Behavioral: Cognitive Testing | |
| Magnetic Resonance Imaging | All subjects will have one MRI with a possibility of one functional MRI (fmri). Receives: Other: MRI | |
| Positron Emission Tomography | All subjects will have PET scan using FPEB or ABP688. Receives: Radiation: PET |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evidence of glutamate availability (mGluR5) in psychiatric disorders confirmed by MRI and PET data.
Measured: Through study completion date, an average of 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2016 (estimated)
- Study start21 Feb 2012
- Primary completion13 Jan 2022
- Study completion13 Jan 2022
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 Yale UniversityThe 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
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- VA Office of Research and Development
- Responsible party
- Sponsor
- Investigators
- Irina Esterlis, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02727972
- Sponsor's protocol ID
- 1101007933
- Other IDs
- 1R01MH104459-01
- Status last verified
- Aug 2026
- First submitted
- 17 Mar 2016
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- 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 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Examination of Glutamate and mGluR5 in Psychiatric Disorders
- ClinicalTrials.gov ID
- NCT02727972
- Acronym / sponsor ID
- 1101007933
- Keywords
- depression, bipolar, post-traumatic stress disorder, mood disorders, PET, mGluRr, glutamate system, MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- VA Office of Research and Development
- Study start
- 21 Feb 2012 (actual)
- Primary completion
- 13 Jan 2022 (actual)
- Study completion
- 13 Jan 2022 (actual)
- First posted
- 5 Apr 2016 (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.
This research study is designed to look at the involvement of the glutamate system in depression. Each subject will undergo a screening appointment to determine study eligibility. Thereafter, the study will take 2 or 3 visits depending on schedule availability and will consist of one MRI scan, and PET scan. Subjects will also participate in cognitive testing. Depending on camera time, staff availability and subject schedule, total study participation may last 1-2 months.
Detailed description
With the recent advancements in positron emission tomography (PET) and radioligand development, the investigators are now able to image and quantify the metabotropic glutamatergic system (mGluR5) in vivo in human subjects. The study proposes a novel investigation of mGluR5 in depression to obtain critical data to advance understanding of the etiology of depression and its associated symptoms of cognitive dysfunction.
Aim 1: To determine mGluR5 availability in individuals with mood disorders compared to healthy controls as measured with PET brain imaging.
Hypothesis 1: The study hypothesizes a decrease in mGluR5 availability in individuals with mood disorders in regions responsible for emotional and cognitive processes, including the amygdala, hippocampus, thalamus, anterior cingulate, and frontal cortices.
Aim 2: To determine if glutamate cycling in individuals with mood disorders is altered as compared to healthy controls as measured with [1H]MRS and [13C]MRS.
Hypothesis 2: The study hypothesizes an increase in glutamate number in individuals with mood disorders as compared to controls.
Aim 3: To determine if the PET alterations in the glutamatergic system of depressed individuals are associated with cognitive deficits observed in depression, including concentration, attention, memory, distractibility, and startle.
Hypothesis 3: The study hypothesizes a positive relationship between mGluR5 availability and cognitive functioning, such that individuals with higher receptor availability will perform better on tests of concentration, attention, memory, distractibility, and startle than individuals with lower receptor availability.
Aim 4: To determine mGluR5 availability in individuals with anxiety and schizophrenia compared to healthy controls as measured with PET brain imaging.
Hypothesis 4: Anxiety disorders such as obsessive compulsive disorder, and delusional disorders such as schizophrenia are frequently comorbid with mood disorders, and the glutamatergic system has been observed to be compromised in these individuals as well. This study will examine if there are regional differences in mGluR5 availability between individuals with depression, bipolar disorder, obsessive compulsive disorder, and schizophrenia.
Aim 5: To examine whether changes in mGluR5 availability are dependent on state, or whether the lower availability is due to trait.
Hypothesis 5: Due to changes in endogenous GLU shown with MRS studies, this study hypothesizes normalization (or increase) in mGluR5 availability in euthymia as compared to depressed state.
Study design
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cognitive Testing | – | Behavioral: Cognitive TestingCognitive assessments |
| Magnetic Resonance Imaging | – | Other: MRIAll subjects will have one MRI with a possibility of one functional MRI (fmri). |
| Positron Emission Tomography | – | Radiation: PETAll subjects will have PET scan using FPEB or ABP688. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subjects will be between the ages of 18-70 years old
- English speaking
- No other DSM-5 diagnosis present, besides required as below
- Clinical diagnosis of a current depressive episode
- Medication-free for at least 2 weeks or medicated with a permissible medication
Key exclusion criteria (9 listed)
- Have a current or past significant medical, neurological or metabolic disorder or head injury that lead to significant long term decline in cognitive abilities as seen by decline in grades or work performance
- Have significant medical illness such that would contraindicate study participation based on above criteria and PI/MD history review
- Have active, significant suicidal ideation
- Have implanted metallic devices or any MR contraindications
- Are women who are pregnant or breastfeeding
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 |
|---|---|---|
| Cognitive TestingVerbal assessments as well as computer testing. | Behavioural | Cognitive Testing |
| MRIAlso: Magnetic Resonance ImagingAnatomical MRIs will be performed on a Siemens 3T Trio at Yale. MR acquisition will be a Sag 3D magnetization-prepared rapid gradient-echo (MPRAGE) sequence with 3.34 ms echo time, 2,500 ms repetition time, 1,000 ms inversion time, 7 degree flip angle, and 180 Hz/pixel bandwidth. The image dimensions will be 256 x 256 x 176 and pixel size 0.98 x 0.98 x 1.0 mm. Resting state MRIs will also be obtained as follows: We will be doing 2 six minute scans with subjects in the scanner, eyes open, fixating a cross. TR = 3 secs 45 slices x 3 mm slice thickness = 13.5 cm. In plane resolution = 3 x 3 mm, slice acquisition order = ascending. | Other | Magnetic Resonance Imaging |
| PETAlso: Positron Emission TomographyHigh Resolution Research Tomograph (HRRT), the highest resolution human brain scanner available, or HR+ will be used to image subjects. Vital signs (blood pressure, pulse, respiration) will be obtained before and after radiotracer administration. An antecubital venous catheter will be used for IV administration of the radiotracer and for venous blood sampling. A radial artery catheter will be inserted by an experienced physician before the PET scan. At the beginning of each scan, the subject's head will be immobilized and a 6 minute transmission scan using an orbiting 137Cs (HRRT) or 68GE (HR+) point-source is obtained and used for attenuation correction. PET scans will be acquired using bolus or bolus plus constant infusion administration of FPEB or ABP688. | Radiation | Positron Emission Tomography |
Primary outcome
Evidence of glutamate availability (mGluR5) in psychiatric disorders confirmed by MRI and PET data.
Time frame: Through study completion date, an average of 4 years.
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 14 Aug 2026.
- 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.
Irina Esterlis, PhD principal investigator
Yale University
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 Post-Traumatic Stress Disorder, run by Yale University 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 9 inclusion and 9 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 14 Aug 2026. 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?
Evidence of glutamate availability (mGluR5) in psychiatric disorders confirmed by MRI and PET data. (time frame: Through study completion date, an average of 4 years.). 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 14 Aug 2026.