PET Biomarkers in Treatment Resistant Depression

• Sponsor: New York State Psychiatric Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01031810
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 13
• Location: 1
• Arm: 1
• Duration (Months): 40
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: tranylcypromine	Phase 4

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

• Study Type: Interventional
• Actual Enrollment: 13 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Developing a Biomarker to Predict Response in Treatment Resistant Depression
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Other: tranylcypromine patients will receive treatment with tranylcypromine	Drug: tranylcypromine; MAO-Inhibitor 60mg-120mg; Other Names: Parnate

Outcome Measures

Primary Outcome Measures

1. Hamilton Depression Rating Scale Scores 17 at Baseline [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.

2. Hamilton Depression Rating Scale Scores 17 at week12 [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.

Secondary Outcome Measures

1. Quick Inventory of Depression- Self Report 16 [Weeks 00]

   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

2. Quick Inventory of Depression- Self Report 16 [Week 04]

   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

3. Quick Inventory of Depression- Self Report 16 [Week 12]

   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

4. Quick Inventory of Depression- Self Report 16 [Week 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New York State Psychiatric Institute	New York	New York	United States	10032

Sponsors and Collaborators

• New York State Psychiatric Institute
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Patrick J McGrath, MD, New York State Psychiatric Institute, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: New York State Psychiatric Institute
• ClinicalTrials.gov Identifier: NCT01031810
• Other Study ID Numbers: 6025; RC1MH088405-01
• First Posted: Dec 15, 2009
• Last Update Posted: Sep 18, 2014
• Last Verified: Oct 1, 2013

• Keywords provided by New York State Psychiatric Institute: Treatment Resistant depression; Major Depression; MDD; Depression
• Additional relevant MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Tranylcypromine

Study Results

Participant Flow

Arm/Group Title	Tranylcypromine
Arm/Group Description	Patients will receive treatment with tranylcypromine tablets taken orally on a twice daily schedule. Dosage was initially 10 mg daily and was increased weekly up to 120 mg daily.
Period Title: Overall Study
STARTED	13
COMPLETED	9
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine
Overall Participants	13
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.3 (10.5)
Sex: Female, Male (Count of Participants)
Female	8 61.5%
Male	5 38.5%
Region of Enrollment (participants) [Number]
United States	13 100%

Outcome Measures

1. Primary Outcome

Title	Hamilton Depression Rating Scale Scores 17 at Baseline
Description	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.
Time Frame	Week 00 (baseline)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine Baseline Hamd17
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	23.2 (5.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tranylcypromine
	Comments	Compare the mean differences between baseline (week00) and week12 hamd17 summary scores
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	paired t-test 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.56
	Confidence Interval	(2-Sided) 95%; 3.25 to 19.86
	Parameter Dispersion	Type: Standard Deviation; Value: 10.81
	Estimation Comments

2. Secondary Outcome

Title	Quick Inventory of Depression- Self Report 16
Description	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
Time Frame	Weeks 00

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine tranylcypromine: monoamine oxidase inhibitor (MAOI) 60mg-120mg
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	17.78 (3.03)

3. Secondary Outcome

Title	Quick Inventory of Depression- Self Report 16
Description	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
Time Frame	Week 04

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine tranylcypromine: MAO-Inhibitor 60mg-120mg
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	13.0 (6.27)

4. Secondary Outcome

Title	Quick Inventory of Depression- Self Report 16
Description	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
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine tranylcypromine: MAO-Inhibitor 60mg-120mg
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	10.38 (5.04)

5. Secondary Outcome

Title	Quick Inventory of Depression- Self Report 16
Description	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
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine tranylcypromine: MAO-Inhibitor 60mg-120mg
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	9.89 (5.23)

6. Primary Outcome

Title	Hamilton Depression Rating Scale Scores 17 at week12
Description	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.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine Baseline Hamd17
Measure Participants	9
Mean (Standard Deviation) [Score on a scale]	11.67 (6.29)

Adverse Events

Time Frame	Adverse event data were collected weekly from baseline(week 00) to week 16.
Arm/Group Title	Tranylcypromine
Arm/Group Description	patients will receive treatment with tranylcypromine
All Cause Mortality
	Tranylcypromine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Tranylcypromine
	Affected / at Risk (%)	# Events
Total	0/9 (0%)
Other (Not Including Serious) Adverse Events
	Tranylcypromine
	Affected / at Risk (%)	# Events
Total	5/9 (55.6%)
Gastrointestinal disorders
Constipation	4/9 (44.4%)	4
General disorders
Dizziness	4/9 (44.4%)	5

Limitations/Caveats

Early termination leading to small numbers of subjects analyzed

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.