Major Depressive DisorderPhase 4NCT01031810
PET Biomarkers in Treatment Resistant Depression
A Phase 4 study testing tranylcypromine in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
The primary objectives of the study are to test whether brain Mono Amine Oxidase-A (MAO-A) levels are elevated in patients with treatment-resistant major depression, and to explore whether MAO-A brain levels predict treatment outcome with Mono Amine Oxidase Inhibitor (MAOI) medication in this population. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- tranylcypromine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to Mar 2013
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Primary diagnosis of Major Depressive Disorder
- Subjects aged 18-65
- Depressed subjects must have Treatment-Resistant Depression (TRD) two previous adequate antidepressant treatment trial failures within the current depressive episode from different classes
- Minimum baseline Montgomery Asberg Depression Rating Scale (MADRS) score of 22
- Signs informed consent form
- Subjects must be willing to be have a PET scan
- Subjects must be antidepressant medication free for 3 weeks prior to PET scan
Who cannot join
- Significant past or present neurological disorder, including seizures, stroke, or head trauma
- History of bipolar disorder, psychosis, schizoaffective disorder, or schizophrenia
- Moderate or high level of suicide risk, as determined by a score of 3 or 4 on item 3 of the HAM-D scale. Also excluded will be those who present a significant suicide risk by history or current psychiatrist's assessment.
- Personality disorder which might interfere with compliance or increase suicide risk
- Alcohol or drug abuse or dependence in the past year; history of lifetime IV drug use or use of methylene diamine methamphetamine (MDMA or "ecstasy") more than twice
- Current thyroid dysfunction (past or currently treated dysfunction is acceptable)
Show all 21Show fewer
- Clinically significant or unstable medical conditions or laboratory abnormalities, including hypertension (repeated BP > 140 systolic, > 90 diastolic)
- Intake of investigational (unapproved) drug in the past 3 months
- Electroconvulsive therapy (ECT) in three months prior to screening
- Use of Vagal Nerve Stimulation (VNS)
- Positive drug of abuse screen
- Anticoagulant treatment which cannot be discontinued for 10 days prior to PET scanning
- Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
- Dementia (clinical and neurocognitive criteria)
- Claustrophobia of a severity which would not permit the participant to undergo an MRI or a PET scan
- Recent (< 7 days) consumption of Ayahuasca Tea or other South American non-standard decoction.
- Presence of metallic devices, implants and other contraindications to scanning
- Current, past or anticipated exposure to radiation, that may include being badged for radiation exposure in the workplace or participation in nuclear medicine research protocols
- Smokers (use of tobacco products in the previous 3 months)
- Potential participants having taken an antidepressant medication in the last 3 weeks. Participants otherwise eligible may elect to discontinue medication which has not been significantly helpful according to their report, their current psychiatrist's report (if available), and the evaluating psychiatrist. No patient will be asked to discontinue an effective antidepressant medication to participate.
- History of previous MAO-I treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Developing a Biomarker to Predict Response in Treatment Resistant Depression
The primary objectives of the study are to test whether brain Mono Amine Oxidase-A (MAO-A) levels are elevated in patients with treatment-resistant major depression, and to explore whether MAO-A brain levels predict treatment outcome with Mono Amine Oxidase Inhibitor (MAOI) medication in this population.
Read the detailed description
While Major Depressive Disorder (MDD) is prevalent and disabling, compelling recent data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study indicate that only about half of patients attain remission from MDD, even after multiple antidepressant medication trials. Further, no biomarker has been validated which can select an effective treatment for such patients, presenting critical unmet intellectual and clinical challenges. The recent landmark finding of an markedly elevated level of monoamine oxidase A (MAO-A) in the brains of depressed patients with MDD compared to controls, using positron emission tomography (PET) with a positron-emitting carbon isotope, (carbon 11 [11C]) labeled monoamine oxidase inhibitor (MAOI), has provided an unparalleled opportunity to address these challenges. It has long been known that MAOIs are effective for some patients with treatment-resistant MDD, although their side effect profile makes them highly unacceptable both to patients and physicians, severely curtailing their utility.
This study seeks to: 1) replicate this study using PET scans in 20 subjects with MDD but extending it to patients with treatment-resistant depression (TRD). (Results from these participants with be compared to those from 10 non-depressed controls; 2) explore the correlation of the brain MAO-A level biomarker to treatment outcome by treating the 20 PET-imaged TRD patients with an MAOI, hypothesizing that their MAOI response will be related to their level of MAO-A. Brain MAO-A is an ideal candidate biomarker for this study since it appears to be significantly abnormally elevated in MDD, yet it has a broad range of values even among depressed patients. Most importantly, the MAO-A biomarker is known to be the single pharmacologic target of the treatment, making it appear likely that outcome with MAOI treatment will be related to MAO-A.
- Conditions
- Major Depressive Disorder
- Being tested
- tranylcypromine
- Keywords
- Treatment Resistant depression, Major Depression, MDD, Depression
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tranylcypromineDrug
Also called Parnate
MAO-Inhibitor 60mg-120mg
| Study group | Role | What they receive |
|---|---|---|
| tranylcypromine | Other | patients will receive treatment with tranylcypromine Receives: Drug: tranylcypromine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Rating Scale Scores 17 at Baseline
HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor.
Scale range (0-52):
A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.
Measured: Week 00 (baseline)
Hamilton Depression Rating Scale Scores 17 at week12
HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor.
Scale range (0-52):
A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.
Measured: Week 12
Secondary outcomes (4)
Quick Inventory of Depression- Self Report 16
Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit
Scale range (0-27):
Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16
Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression
Measured: Weeks 00
Quick Inventory of Depression- Self Report 16
Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit
Scale range (0-27):
Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16
Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression
Measured: Week 04
Quick Inventory of Depression- Self Report 16
Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit
Scale range (0-27):
Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16
Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression
Measured: Week 12
Quick Inventory of Depression- Self Report 16
Quick Inventory of Depression- Self Report assesses 16 depressive symptoms experienced in the past week, based on self-rating, measured at study exit visit
Scale range (0-27):
Each of the four possible answers to each quiz is given an ascending numerical value from 0 to 3, and the total test score is the sum of the following: The highest number from questions 1-4 The number from question 5 The highest number from questions 6-9 The total of each question from 10-14 The highest number from questions 15-16
Total score interpretation: 0-5 no depression, 6-10 mild depression, 11-15 moderate depression, 16-20 severe depression, 20 and above very severe depression
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2009 (estimated)
- Study startNov 2009
- Primary completionMar 2013
- Study completionMar 2013
Why it stopped: Needed PET facility closed
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 Major Depressive DisorderStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Patrick J McGrath, MD, Principal investigator, New York State Psychiatric Institute, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01031810
- Sponsor's protocol ID
- 6025
- Other IDs
- RC1MH088405-01
- Status last verified
- Oct 2013
- First submitted
- 12 Dec 2009
- Last updated
- 18 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing a Biomarker to Predict Response in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT01031810
- Acronym / sponsor ID
- 6025
- Conditions
- Major Depressive Disorder
- Keywords
- Treatment Resistant depression, Major Depression, MDD, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Needed PET facility closed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Nov 2009
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 15 Dec 2009 (estimated)
- Results
- Posted 18 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives of the study are to test whether brain Mono Amine Oxidase-A (MAO-A) levels are elevated in patients with treatment-resistant major depression, and to explore whether MAO-A brain levels predict treatment outcome with Mono Amine Oxidase Inhibitor (MAOI) medication in this population.
Detailed description
While Major Depressive Disorder (MDD) is prevalent and disabling, compelling recent data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study indicate that only about half of patients attain remission from MDD, even after multiple antidepressant medication trials. Further, no biomarker has been validated which can select an effective treatment for such patients, presenting critical unmet intellectual and clinical challenges. The recent landmark finding of an markedly elevated level of monoamine oxidase A (MAO-A) in the brains of depressed patients with MDD compared to controls, using positron emission tomography (PET) with a positron-emitting carbon isotope, (carbon 11 [11C]) labeled monoamine oxidase inhibitor (MAOI), has provided an unparalleled opportunity to address these challenges. It has long been known that MAOIs are effective for some patients with treatment-resistant MDD, although their side effect profile makes them highly unacceptable both to patients and physicians, severely curtailing their utility.
This study seeks to: 1) replicate this study using PET scans in 20 subjects with MDD but extending it to patients with treatment-resistant depression (TRD). (Results from these participants with be compared to those from 10 non-depressed controls; 2) explore the correlation of the brain MAO-A level biomarker to treatment outcome by treating the 20 PET-imaged TRD patients with an MAOI, hypothesizing that their MAOI response will be related to their level of MAO-A. Brain MAO-A is an ideal candidate biomarker for this study since it appears to be significantly abnormally elevated in MDD, yet it has a broad range of values even among depressed patients. Most importantly, the MAO-A biomarker is known to be the single pharmacologic target of the treatment, making it appear likely that outcome with MAOI treatment will be related to MAO-A.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tranylcypromine | Other | Drug: tranylcyprominepatients will receive treatment with tranylcypromine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Primary diagnosis of Major Depressive Disorder
- Subjects aged 18-65
- Depressed subjects must have Treatment-Resistant Depression (TRD) two previous adequate antidepressant treatment trial failures within the current depressive episode from different classes
- Minimum baseline Montgomery Asberg Depression Rating Scale (MADRS) score of 22
- Signs informed consent form
Key exclusion criteria (21 listed)
- Significant past or present neurological disorder, including seizures, stroke, or head trauma
- History of bipolar disorder, psychosis, schizoaffective disorder, or schizophrenia
- Moderate or high level of suicide risk, as determined by a score of 3 or 4 on item 3 of the HAM-D scale. Also excluded will be those who present a significant suicide risk by history or current psychiatrist's assessment.
- Personality disorder which might interfere with compliance or increase suicide risk
- Alcohol or drug abuse or dependence in the past year; history of lifetime IV drug use or use of methylene diamine methamphetamine (MDMA or "ecstasy") more than twice
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 |
|---|---|---|
| tranylcypromineAlso: ParnateMAO-Inhibitor 60mg-120mg | Drug | tranylcypromine |
Primary outcome
Hamilton Depression Rating Scale Scores 17 at Baseline
Time frame: Week 00 (baseline)
HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor. Scale range (0-52): A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.
Hamilton Depression Rating Scale Scores 17 at week12
Time frame: Week 12
HAM-D is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. Each item on the questionnaire is scored on a 3 or 5 point scale, depending on the item, and the total score is compared to the corresponding descriptor. Scale range (0-52): A score of 0-7 is considered to be normal. Scores of 20 or higher indicate moderate, severe, or very severe depression, and are usually required for entry into a clinical trial.
4 secondary outcomes
Quick Inventory of Depression- Self Report 16
Time frame: Weeks 00
Quick Inventory of Depression- Self Report 16
Time frame: Week 04
Quick Inventory of Depression- Self Report 16
Time frame: Week 12
Quick Inventory of Depression- Self Report 16
Time frame: Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Depression Evaluation Service websiteLink provided by the sponsor.
- New York State Psychiatric Institute official websiteLink provided by the sponsor.
- Columbia University Psychiatry websiteLink provided by the sponsor.
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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.
Patrick J McGrath, MD principal investigator
New York State Psychiatric Institute, Columbia University
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 tranylcypromine in people with Major Depressive Disorder, run by New York State Psychiatric Institute 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 7 inclusion and 21 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: stopped early, as of the sponsor's last update on 18 Sep 2014. 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 18 Sep 2014). 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?
Hamilton Depression Rating Scale Scores 17 at Baseline (time frame: Week 00 (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 18 Sep 2014.