Depressive DisorderPhase 1NCT01568684
Brain Imaging, Genetics and Treatment for Major Depression
A Phase 1 study testing Citalopram in people with Depressive Disorder and Depressive Disorder, Major, run by National Institute of Mental Health (NIMH).
Trial summary
Background: Antidepressants help many people with depression, however, some do not seem to benefit as much. Currently, it is not possible to determine who will improve with certain antidepressants. Studies have shown that genes may influence whether an antidepressant works for an individual. Read more about this study
- Who is it for?
- Ages 25 to 55 years
- Conditions the study is for
- Depressive Disorder, Depressive Disorder, Major, Depression
- What is being tested?
- Citalopram
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 12 Mar 2012to 11 Dec 2012
- Phase
- Phase 1
- 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 25 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male and female subjects aged between 25 and 55 years
- Score of 18 or higher on the 17-item Hamilton Depression Rating Scale (HDRS17). We have set the HDRS17 cutoff score to greater than or equal to18 to increase the contrast signals between remitters and non-remitters, MRS imaging and genotypic groups.
- Meets DSM-IV criteria for chronic or recurrent non-psychotic MDD
- No more than 3 failed FDA-approved antidepressant treatments within the current episode
- No alcohol use in the last 7 days
- Fluent in English or Spanish
- Capacity to understand the nature of the study and provide informed consent
Who cannot join
- Lifetime history of schizophrenia, schizoaffective disorder or psychosis not otherwise specified
- Lifetime history of bipolar disorder (I, II, or not otherwise specified)
- Lifetime history of anorexia nervosa or bulimia nervosa
- Current primary obsessive-compulsive disorder (OCD)
- History of intolerability to citalopram
- Lack of response to an adequate trial of citalopram or escitalopram in the current or previous episodes of MDD
Show all 24Show fewer
- Have failed to respond to more than three antidepressants during current major depressive episode
- Lack of response to 7 or more sessions of ECT in the current or previous episodes of MDD
- Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
- Females who are sexually active and who are not willing to use effective contraception for 8-weeks while participating in this study or are pregnant or breast feeding
- Concomitant medication use which contraindicates the use of the study medication
- Requires any of the following exclusionary medications: antipsychotic medications, anticonvulsant medications, antidepressant medications, mood stabilizers, central nervous system stimulants
- Patients on thyroid medication for hypothyroidism: stable on thyroid medication for < 2 months
- Current participation in any modality of psychotherapy and the patient is not willing to forgo it during participation
- Have a history of drug or alcohol dependence or current abuse within the last 3 months
- Past history of significant head injury with loss of consciousness for about 24 hours or more
- Current or past history of seizure disorder
- Suicidal ideation with plan and/or intent
- Have received any investigational drug within the last 30 days
- Metallic (ferromagnetic) implants, including pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pump, shrapnel fragments, and possible small metal fragments in the eye
- Unable to lie flat on back for up to 2 hours
- Claustrophobia in scanner
- Positive drug screen
- HIV-positive.
About this study
Official title: Pharmacogenetics and Neuroimaging in Major Depressive Disorder (PAN-D)
Background:
- Antidepressants help many people with depression, however, some do not seem to benefit as much. Currently, it is not possible to determine who will improve with certain antidepressants. Studies have shown that genes may influence whether an antidepressant works for an individual. Other studies have shown that depressed people tend to have lower levels of a chemical called glutamate in parts of their brain, and that glutamate levels increase after recovering from depression. Researchers want to study the antidepressant citalopram (Celexa) to see how it affects glutamate levels in the brain. They also want to study how a person s genes affect their response to this treatment.
Read more
Objectives:
- To see whether glutamate levels and certain genes affect how a person responds to a particular antidepressant medication.
Eligibility:
- Individuals between 25 and 55 years of age who have been diagnosed with major depression (without psychotic features). Participants may not have tried more than three antidepressant treatments.
Design:
- Participants will be screened with a physical exam and medical history. They will answer questions about mood and current feelings of depression, as well as family history of depression. Blood and urine samples will be collected.
- This study will have two phases. The first phase may last up to 7 weeks depending on current antidepressant use and involves one to seven outpatient visits. The second phase lasts 8 weeks and involves five outpatient visits, one every 2 weeks.
- In the first phase, participants will stop taking their current antidepressant medications for at least 2 weeks before the next phase of the study. Participants who are on fluoxetine (Prozac) will need to be off it for 6 weeks.
- At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.
- In the second phase, participants will take citalopram at the standard dose. They will answer questions about mood and response to the medication. They will also provide blood and saliva samples for tests.
- At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.
Read the detailed description
Objective:
Major depressive disorder (MDD) is a serious, debilitating, life-shortening illness that affects many persons of all ages and backgrounds. Although many patients suffering from MDD can expect improvement with antidepressant treatment, only a minority experience full remission, and little is known about the basis for individual differences in treatment outcome. The rationale for this study follows from the findings that treatment response in major depression is associated with: 1) variation in the genes encoding the serotonin 2A receptor (HTR2A) and the KA1 subunit of the glutamate-kainate receptor (GRIK4); and 2) increases in prefrontal glutamate/glutamine (glx) concentration measured by [+H] magnetic resonance spectroscopy (MRS). The central hypothesis is that genes associated with citalopram treatment outcome modulate glutamate concentrations in prefrontal brain (PFB) and thus facilitate response to citalopram treatment. Such information is important because it would ultimately allow the development of better treatments for MDD.
Study population:
A total of 104 moderate to severe MDD outpatients aged 25-55 with a baseline 17-item Hamilton Depression Rating Scale (HDRS) score of greater than or equal to18 who meet DSM-IV criteria for non-psychotic major depressive disorder (MDD) will be enrolled in the course of the study.
Design:
Subjects will be screened with an on-site research psychiatric evaluation using a structured interview (MINI plus). After screening, participants will provide a DNA sample, which will be analyzed to determine the patient s genotype at several relevant loci. All patients will then complete an eight-week period of citalopram treatment, during which time they will be evaluated bi-weekly with self-report questionnaires and clinician ratings to determine change of MDD symptoms. Participants will also undergo pre- and post-treatment MRS scans to determine glutamate concentration in the prefrontal brain.
Treatment outcome measures:
The Quick Inventory of Depressive Symptomatology - Clinician-Rated (QIDS-C16) will be the primary clinical outcome measure and will be collected at baseline and at each treatment visit. Additionally, levels of glutamate in the prefrontal regions of the brain will be measured by MRS. Clinical response will be defined as a decrease of 50 percent or greater in QIDS-C16 score from baseline, and remission will be defined as a QIDS-C16 score of less than 6.
This proposal is part of a K99 training grant and has undergone extensive external review (K99MH085098-01A2).
- Conditions
- Depressive Disorder, Depressive Disorder, Major, Depression
- Being tested
- Citalopram
- Keywords
- Magnetic Resonance Spectroscopy, Depression, Depression Treatment, Major Depression, Unipolar Depression
- Medical subject headings
- Depressive Disorder, Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CitalopramOther
Treatment
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in prefrontal glutamate concentration after citalopram treatment.
Secondary outcomes (2)
Changes in depressive symptoms after citalopram treatment.
Association between glutamate changes and genetic variation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2012 (estimated)
- Study start12 Mar 2012
- Primary completion11 Dec 2012
- Study completion11 Dec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
- Investigators
- Gonzalo Laje, M.D., Principal investigator, National Institute of Mental Health (NIMH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01568684
- Sponsor's protocol ID
- 120099
- Other IDs
- 12-M-0099
- Status last verified
- 11 Dec 2012
- First submitted
- 30 Mar 2012
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Caetano SC, Fonseca M, Olvera RL, Nicoletti M, Hatch JP, Stanley JA, Hunter K, Lafer B, Pliszka SR, Soares JC. Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients. Neurosci Lett. 2005 Aug 26;384(3):321-6. doi: 10.1016/j.neulet.2005.04.099.
PubMed 15936878Cho MK. Understanding incidental findings in the context of genetics and genomics. J Law Med Ethics. 2008 Summer;36(2):280-5, 212. doi: 10.1111/j.1748-720X.2008.00270.x.
PubMed 18547195HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.
PubMed 13638508
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetics and Neuroimaging in Major Depressive Disorder (PAN-D)
- ClinicalTrials.gov ID
- NCT01568684
- Acronym / sponsor ID
- 120099
- Conditions
- Depressive Disorder, Depressive Disorder, Major, Depression
- Keywords
- Magnetic Resonance Spectroscopy, Depression, Depression Treatment, Major Depression, Unipolar Depression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 12 Mar 2012
- Primary completion
- 11 Dec 2012 (actual)
- Study completion
- 11 Dec 2012 (actual)
- First posted
- 2 Apr 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.
Background:
- Antidepressants help many people with depression, however, some do not seem to benefit as much. Currently, it is not possible to determine who will improve with certain antidepressants. Studies have shown that genes may influence whether an antidepressant works for an individual. Other studies have shown that depressed people tend to have lower levels of a chemical called glutamate in parts of their brain, and that glutamate levels increase after recovering from depression. Researchers want to study the antidepressant citalopram (Celexa) to see how it affects glutamate levels in the brain. They also want to study how a person s genes affect their response to this treatment.
Objectives:
- To see whether glutamate levels and certain genes affect how a person responds to a particular antidepressant medication.
Eligibility:
- Individuals between 25 and 55 years of age who have been diagnosed with major depression (without psychotic features). Participants may not have tried more than three antidepressant treatments.
Design:
- Participants will be screened with a physical exam and medical history. They will answer questions about mood and current feelings of depression, as well as family history of depression. Blood and urine samples will be collected.
- This study will have two phases. The first phase may last up to 7 weeks depending on current antidepressant use and involves one to seven outpatient visits. The second phase lasts 8 weeks and involves five outpatient visits, one every 2 weeks.
- In the first phase, participants will stop taking their current antidepressant medications for at least 2 weeks before the next phase of the study. Participants who are on fluoxetine (Prozac) will need to be off it for 6 weeks.
- At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.
- In the second phase, participants will take citalopram at the standard dose. They will answer questions about mood and response to the medication. They will also provide blood and saliva samples for tests.
- At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry.
Detailed description
Objective:
Major depressive disorder (MDD) is a serious, debilitating, life-shortening illness that affects many persons of all ages and backgrounds. Although many patients suffering from MDD can expect improvement with antidepressant treatment, only a minority experience full remission, and little is known about the basis for individual differences in treatment outcome. The rationale for this study follows from the findings that treatment response in major depression is associated with: 1) variation in the genes encoding the serotonin 2A receptor (HTR2A) and the KA1 subunit of the glutamate-kainate receptor (GRIK4); and 2) increases in prefrontal glutamate/glutamine (glx) concentration measured by [+H] magnetic resonance spectroscopy (MRS). The central hypothesis is that genes associated with citalopram treatment outcome modulate glutamate concentrations in prefrontal brain (PFB) and thus facilitate response to citalopram treatment. Such information is important because it would ultimately allow the development of better treatments for MDD.
Study population:
A total of 104 moderate to severe MDD outpatients aged 25-55 with a baseline 17-item Hamilton Depression Rating Scale (HDRS) score of greater than or equal to18 who meet DSM-IV criteria for non-psychotic major depressive disorder (MDD) will be enrolled in the course of the study.
Design:
Subjects will be screened with an on-site research psychiatric evaluation using a structured interview (MINI plus). After screening, participants will provide a DNA sample, which will be analyzed to determine the patient s genotype at several relevant loci. All patients will then complete an eight-week period of citalopram treatment, during which time they will be evaluated bi-weekly with self-report questionnaires and clinician ratings to determine change of MDD symptoms. Participants will also undergo pre- and post-treatment MRS scans to determine glutamate concentration in the prefrontal brain.
Treatment outcome measures:
The Quick Inventory of Depressive Symptomatology - Clinician-Rated (QIDS-C16) will be the primary clinical outcome measure and will be collected at baseline and at each treatment visit. Additionally, levels of glutamate in the prefrontal regions of the brain will be measured by MRS. Clinical response will be defined as a decrease of 50 percent or greater in QIDS-C16 score from baseline, and remission will be defined as a QIDS-C16 score of less than 6.
This proposal is part of a K99 training grant and has undergone extensive external review (K99MH085098-01A2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male and female subjects aged between 25 and 55 years
- Score of 18 or higher on the 17-item Hamilton Depression Rating Scale (HDRS17). We have set the HDRS17 cutoff score to greater than or equal to18 to increase the contrast signals between remitters and non-remitters, MRS imaging and genotypic groups.
- Meets DSM-IV criteria for chronic or recurrent non-psychotic MDD
- No more than 3 failed FDA-approved antidepressant treatments within the current episode
- No alcohol use in the last 7 days
Key exclusion criteria (24 listed)
- Lifetime history of schizophrenia, schizoaffective disorder or psychosis not otherwise specified
- Lifetime history of bipolar disorder (I, II, or not otherwise specified)
- Lifetime history of anorexia nervosa or bulimia nervosa
- Current primary obsessive-compulsive disorder (OCD)
- History of intolerability to citalopram
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 |
|---|---|---|
| CitalopramTreatment | Other | – |
Primary outcome
Changes in prefrontal glutamate concentration after citalopram treatment.
2 secondary outcomes
Changes in depressive symptoms after citalopram treatment.
Association between glutamate changes and genetic variation.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 15936878Caetano SC, Fonseca M, Olvera RL, Nicoletti M, Hatch JP, Stanley JA, Hunter K, Lafer B, Pliszka SR, Soares JC. Proton spectroscopy study of the left dorsolateral prefrontal cortex in pediatric depressed patients. Neurosci Lett. 2005 Aug 26;384(3):321-6. doi: 10.1016/j.neulet.2005.04.099.
- Background: PubMed 18547195Cho MK. Understanding incidental findings in the context of genetics and genomics. J Law Med Ethics. 2008 Summer;36(2):280-5, 212. doi: 10.1111/j.1748-720X.2008.00270.x.
- Background: PubMed 13638508HAMILTON M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-5. doi: 10.1111/j.2044-8341.1959.tb00467.x. No abstract available.
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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.
Gonzalo Laje, M.D. principal investigator
National Institute of Mental Health (NIMH)
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Citalopram in people with Depressive Disorder and Depressive Disorder, Major, run by National Institute of Mental Health (NIMH).
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 7 inclusion and 24 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: withdrawn, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Changes in prefrontal glutamate concentration after citalopram treatment.. 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 NCT01568684, which also lists 3 linked publications.
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 17 Dec 2019.