MDDPhase 4NCT01557946
Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression
A Phase 4 study testing citalopram in people with MDD and Citalopram, run by Mclean Hospital at 1 site in United States.
Trial summary
Primarily, this study seeks to evaluate whether citalopram treatment is associated with an increase in the Glutamine (Gln)/Glutamate (Glu) ratio in the anterior cingulate cortex (ACC) from baseline to day 3 of treatment. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- MDD, Citalopram, Major Depressive Disorder
- What is being tested?
- citalopram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to Sep 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female age ≥ 18 and ≤ 65
- Meets DSM-IV criteria for MDD
- Current score of ≥ 18 on the 21-item Hamilton Depression Rating Scale (HAM-D).
Who cannot join
- Unwillingness or inability to provide written informed consent.
- Current suicidal ideation
- Active psychotic symptoms
- Lifetime history of bipolar disorder, schizophrenia, or OCD
- Failed treatment with an adequate trial of ≥ 2 antidepressants during the current major depressive episode ("failure" will be defined as ≤ 50% subjective improvement, and an "adequate trial" will be defined as at least 4 weeks of treatment using at least the minimum dose of the antidepressant recommended by the manufacturer in product labeling)
- DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine dependence, within three months prior to screening
Show all 12Show fewer
- Any history of treatment with electroconvulsive therapy
- Positive urine toxicology screen for any drug of abuse or excluded medication at screening. Opiate pain medication being taken for a medical condition is exempt from needing a negative opiate screen.
- Clinically significant medical or neurologic disease, as judged by the principal investigator, which would increase the risk to the participant or interfere with interpretation of results
- Female participants with a positive urine pregnancy test at screening
- 12. Pregnancy. Females of childbearing potential must be using an effective contraceptive method (e.g., abstinence, prescription oral contraceptives, contraceptive injections, double-barrier method, male partner sterilization).
- 13. Any screening laboratory abnormality deemed clinically significant by the investigator 14. A QTc interval on screening ECG of ≥ 450 msec. 15. Use of any excluded medications (see Section 6.7 below) that cannot be discontinued during the screening phase 16. Previous failure to respond to treatment with citalopram that would, in the judgment of the investigator, constitute an adequate trial in MDD 17. Treatment with any investigational medications within 30 days prior to screening 18. Any contraindications to having an MRI scan, including cardiac pacemakers, metal vascular clips or stents, artificial heart valves, certain kinds of prostheses, brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings (wounded in military combat, sheetmetal workers, welders, and others), transdermal drug delivery systems, and certain tattoos with metallic ink 19. Left-handedness
Trial locations and contacts
1 site in 1 country.
About this study
Primarily, this study seeks to evaluate whether citalopram treatment is associated with an increase in the Glutamine (Gln)/Glutamate (Glu) ratio in the anterior cingulate cortex (ACC) from baseline to day 3 of treatment. Additionally, this study would like to examine whether citalopram treatment is associated with an increase in the Gln/Glu ratio in the ACC from baseline to day 7 of treatment. In order to more fully examine baseline neurochemical and functional abnormalities in participants with MDD, we also seek to scan a group of age- and sex-matched non-depressed comparison individuals in order to perform between-group analyses of baseline neuroimaging measures.
Read the detailed description
Little is known about the acute effects of standard antidepressant treatments on brain glutamate and gamma-amino-butyric acid (GABA) levels, and their association with clinical response. In the current study, we used proton magnetic resonance spectroscopy (1H-MRS) to examine longitudinally the effects of citalopram on the glutamine/glutamate ratio and GABA levels in the pregenual anterior cingulate cortex (pgACC) - a region that has been repeatedly implicated in antidepressant response - of individuals with major depressive disorder (MDD). We acquired 1H-MRS scans at baseline and at days 3, 7, and 42 of citalopram treatment in nineteen unmedicated individuals with MDD. Ten age- and sex-matched non-depressed comparison individuals were scanned once and did not receive citalopram. The association between baseline metabolites and the change in metabolites from baseline to each time point and change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 42 was assessed by longitudinal regression analysis, adjusting for age, sex, and baseline MADRS, using generalized estimating equations.
- Conditions
- MDD, Citalopram, Major Depressive Disorder
- Being tested
- citalopram
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
citalopramDrug
Also called Celexa
citalopram 20-40 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Major Depression | Experimental | Participants with major depressive disorder received citalopram 20-40 mg daily for 6 weeks. MRI scans were acquired at baseline and days 3, 7, and 42. Receives: Drug: citalopram |
| Healthy Volunteers | No intervention | Healthy volunteer participants did not receive citalopram and performed one MRI scan. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Difference From Baseline to Day 3 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group
Estimated mean difference (day 3 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 3 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.
Measured: Change from Baseline to Day 3
Secondary outcomes (1)
Mean Difference From Baseline to Day 7 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group
Estimated mean difference (day 7 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 7 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.
Measured: Change from baseline to day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionSep 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MDDStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Open-label administration of citalopram to participants with major depressive disorder. MRI scans performed at baseline and days 3, 7, and 42. An age- and gender-matched group of healthy volunteers did not receive citalopram and received on MRI scan to perform between-group baseline analyses.
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian P. Brennan, MD, Mclean Hospital
- Investigators
- Brian P. Brennan, M.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01557946
- Sponsor's protocol ID
- 2011-P-001192
- Status last verified
- Aug 2017
- First submitted
- 9 Mar 2012
- Last updated
- 12 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression
- ClinicalTrials.gov ID
- NCT01557946
- Acronym / sponsor ID
- 2011-P-001192
- Conditions
- MDD, Citalopram, Major Depressive Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 20 Mar 2012 (estimated)
- Results
- Posted 12 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primarily, this study seeks to evaluate whether citalopram treatment is associated with an increase in the Glutamine (Gln)/Glutamate (Glu) ratio in the anterior cingulate cortex (ACC) from baseline to day 3 of treatment. Additionally, this study would like to examine whether citalopram treatment is associated with an increase in the Gln/Glu ratio in the ACC from baseline to day 7 of treatment. In order to more fully examine baseline neurochemical and functional abnormalities in participants with MDD, we also seek to scan a group of age- and sex-matched non-depressed comparison individuals in order to perform between-group analyses of baseline neuroimaging measures.
Detailed description
Little is known about the acute effects of standard antidepressant treatments on brain glutamate and gamma-amino-butyric acid (GABA) levels, and their association with clinical response. In the current study, we used proton magnetic resonance spectroscopy (1H-MRS) to examine longitudinally the effects of citalopram on the glutamine/glutamate ratio and GABA levels in the pregenual anterior cingulate cortex (pgACC) - a region that has been repeatedly implicated in antidepressant response - of individuals with major depressive disorder (MDD). We acquired 1H-MRS scans at baseline and at days 3, 7, and 42 of citalopram treatment in nineteen unmedicated individuals with MDD. Ten age- and sex-matched non-depressed comparison individuals were scanned once and did not receive citalopram. The association between baseline metabolites and the change in metabolites from baseline to each time point and change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 42 was assessed by longitudinal regression analysis, adjusting for age, sex, and baseline MADRS, using generalized estimating equations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label administration of citalopram to participants with major depressive disorder. MRI scans performed at baseline and days 3, 7, and 42. An age- and gender-matched group of healthy volunteers did not receive citalopram and received on MRI scan to perform between-group baseline analyses.
| Arm | Type | Receives |
|---|---|---|
| Major Depression | Experimental | Drug: citalopramParticipants with major depressive disorder received citalopram 20-40 mg daily for 6 weeks. MRI scans were acquired at baseline and days 3, 7, and 42. |
| Healthy Volunteers | No intervention | –Healthy volunteer participants did not receive citalopram and performed one MRI scan. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female age ≥ 18 and ≤ 65
- Meets DSM-IV criteria for MDD
- Current score of ≥ 18 on the 21-item Hamilton Depression Rating Scale (HAM-D).
Key exclusion criteria (12 listed)
- Unwillingness or inability to provide written informed consent.
- Current suicidal ideation
- Active psychotic symptoms
- Lifetime history of bipolar disorder, schizophrenia, or OCD
- Failed treatment with an adequate trial of ≥ 2 antidepressants during the current major depressive episode ("failure" will be defined as ≤ 50% subjective improvement, and an "adequate trial" will be defined as at least 4 weeks of treatment using at least the minimum dose of the antidepressant recommended by the manufacturer in product labeling)
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 |
|---|---|---|
| citalopramAlso: Celexacitalopram 20-40 mg daily | Drug | Major Depression |
Primary outcome
Mean Difference From Baseline to Day 3 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group
Time frame: Change from Baseline to Day 3
Estimated mean difference (day 3 minus baseline) in the glutamine/glutamate (Gln/Glu) ratio in the rostral anterior cingulate cortex as measured by proton magnetic resonance spectroscopy from baseline to day 3 of citalopram treatment within the depressed group. The change in metabolites from baseline to each time point was assessed by random regression analysis, adjusting for age and sex, using generalized estimating equations to account for the correlation of observations within individuals.
1 secondary outcome
Mean Difference From Baseline to Day 7 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group
Time frame: Change from baseline to day 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Brian P. Brennan, M.D. principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing citalopram in people with MDD and Citalopram, run by Mclean Hospital 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 3 inclusion and 12 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 12 Sep 2017. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Difference From Baseline to Day 3 in Glutamine/Glutamate (Gln/Glu) Ratio Within Depressed Group (time frame: Change from Baseline to Day 3). 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 12 Sep 2017.