PET Biomarkers in Treatment Resistant Depression

Major Depressive Disorder Clinical Trial

Official title:

Developing a Biomarker to Predict Response in Treatment Resistant Depression

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01031810
• Other study ID #: 6025
• Secondary ID: RC1MH088405-01
• Status: Terminated
• Phase: Phase 4
• First received: December 12, 2009
• Last updated: September 15, 2014
• Start date: November 2009
• Est. completion date: March 2013

Study information

• Verified date: October 2013
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder

Intervention

Drug:
• tranylcypromine
MAO-Inhibitor 60mg-120mg

Locations

Country	Name	City	State
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Week 00 (baseline)	No
Primary	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.	Week 12	No
Secondary	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	Weeks 00	No
Secondary	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	Week 04	No
Secondary	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	Week 12	No
Secondary	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	Week 16	No

External Links

•   Columbia University Psychiatry website
•   Depression Evaluation Service website
•   New York State Psychiatric Institute official website