Clinical trial NCT01031810: PET Biomarkers in Treatment Resistant Depression
Official title: Developing a Biomarker to Predict Response in Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: Treatment Resistant depression
Major Depression
MDD
Depression
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2009-12-15
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: INCLUSION:

1. Primary diagnosis of Major Depressive Disorder
2. Subjects aged 18-65
3. Depressed subjects must have Treatment-Resistant Depression (TRD) two previous adequate antidepressant treatment trial failures within the current depressive episode from different classes
4. Minimum baseline Montgomery Asberg Depression Rating Scale (MADRS) score of 22
5. Signs informed consent form
6. Subjects must be willing to be have a PET scan
7. Subjects must be antidepressant medication free for 3 weeks prior to PET scan

EXCLUSION

1. Significant past or present neurological disorder, including seizures, stroke, or head trauma
2. History of bipolar disorder, psychosis, schizoaffective disorder, or schizophrenia
3. 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.
4. Personality disorder which might interfere with compliance or increase suicide risk
5. 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
6. Current thyroid dysfunction (past or currently treated dysfunction is acceptable)
7. Clinically significant or unstable medical conditions or laboratory abnormalities, including hypertension (repeated BP \> 140 systolic, \> 90 diastolic)
8. Intake of investigational (unapproved) drug in the past 3 months
9. Electroconvulsive therapy (ECT) in three months prior to screening
10. Use of Vagal Nerve Stimulation (VNS)
11. Positive drug of abuse screen
12. Anticoagulant treatment which cannot be discontinued for 10 days prior to PET scanning
13. Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months.
14. Dementia (clinical and neurocognitive criteria)
15. Claustrophobia of a severity which would not permit the participant to undergo an MRI or a PET scan
16. Recent (\< 7 days) consumption of Ayahuasca Tea or other South American non-standard decoction.
17. Presence of metallic devices, implants and other contraindications to scanning
18. 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
19. Smokers (use of tobacco products in the previous 3 months)
20. 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.
21. History of previous MAO-I treatment

Primary outcomes:
measure: Hamilton Depression Rating Scale Scores 17 at Baseline
timeFrame: Week 00 (baseline)
measure: Hamilton Depression Rating Scale Scores 17 at week12
timeFrame: Week 12
Secondary outcomes:
measure: Quick Inventory of Depression- Self Report 16
timeFrame: Weeks 00
measure: Quick Inventory of Depression- Self Report 16
timeFrame: Week 04
measure: Quick Inventory of Depression- Self Report 16
timeFrame: Week 12
measure: Quick Inventory of Depression- Self Report 16
timeFrame: Week 16
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
Study officials:
affiliation: New York State Psychiatric Institute, Columbia University
name: Patrick J McGrath, MD
role: PRINCIPAL_INVESTIGATOR
References: