Structural and Functional Connectivity of Brainstem Monoamine Pathways in Treatment Resistant Depression

Treatment Resistant Depression Clinical Trial

— MAOI  

Official title:

Structural and Functional Connectivity of Brainstem Monoamine Pathways in Treatment Resistant Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03109717
• Other study ID #: 15-1372
• Status: Completed
• Start date: July 2016
• Est. completion date: May 2021

Study information

• Verified date: June 2021
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Study TRD subjects' resistance to at least 2 different antidepressants, we hypothesize that because of their significant depression and treatment resistant status they are most likely to exhibit BSMN pathway abnormalities.

Description:

Potential subjects will be identified during clinical visits. If a patient qualifies to participate in the study they will have to stop any antidepressants that they are taking to prepare for the use of MAOIs. After a two week washout period, subjects will have an fMRI and will be started on a MAOI. They will then be followed up for 8 weeks, which is routine and considered standard care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: May 2021
• Est. primary completion date: November 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria - TRD:

1. age: 18 - 65 yrs.;

2. satisfy criteria for DSM-IV major depressive disorder (MDD);

3. 17-item Hamilton Depression Rating Scale (17-item HDRS) score > 18;

4. treatment resistance depression as defined as report of inadequate response (patient report of minimal improvement or nonresponse) despite past treatment with at least 2 different classes of antidepressants acting on the 5-HT and/or DA monoamine systems(except MAOIs) (as determined with the Antidepressant Treatment History Form (ATHF)20 with score of >3 on each of the items and verified by medical records if available);

5. able to give informed consent;

6. no use of alcohol in the past 1 week and negative urine toxicology screen;

7. MAOI treatment indicated as assessed by an independent psychiatrist not affiliated with the study;

8. voluntary consent to treatment with an MAOI after reviewing all other options and agree to follow safeguards and precautions during treatment.

Inclusion criteria for healthy subjects

1. ages 18-65 years and ability to give voluntary informed consent;

2. no history of psychiatric illness or substance abuse or dependence;

3. no significant family history of psychiatric or neurological illness;

4. not currently taking any prescription or centrally acting medications; no use of alcohol in the past 1 week;

5. and no serious medical or neurological illness.

Exclusion Criteria - TRD:

1. schizophrenia, schizoaffective or primary anxiety disorder;

2. serious medical or neurological illness;

3. history of significant head injury;

4. on fluoxetine treatment;

5. on lithium or have received ECT or rTMS in the last 3 months to avoid long-term effects of such medications;

6. substance or alcohol dependence in the past 6 months or substance abuse in the past 3 months;

7. unable to give informed consent.

Exclusion criteria for both groups:

1. pregnant or breast-feeding;

2. metallic implants or other contraindication to MRI.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Monoamine Oxidase Inhibitor (MAOI)
Monoamine Oxidase Inhibitor

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Kathryn O'Connor

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	17-item Hamilton Depression Rating Scale	Compare baseline and end of study Hamilton depression Rating scale and imaging correlations.	2 years
Primary	Brainstem Structural Connectivity (Sc)	Localize BSMN and measure pathway Sc using diffusion imaging to differentiate between TRD and HC. BSMN can be localized using diffusion imaging, and pathways projecting from BSMN to known targets can be identified. Methods have been developed to localize these nuclei via a combination of diffusion imaging and anatomic imaging. We will identify these nuclei and track their projections to known targets, giving rise to the VTA-NAcc, VTA-AMYG, RN-AM and RN-sgACC pathways. Probabilistic fiber tracking between these nodes will be used to determine a measure of pathway strength.	2 years
Primary	Brainstem Functional Connectivity (Fc)	Measure BSMN pathway Fc to differentiate between TRD and HC. BSMN associated with different neuromodulators, e.g. the VTA and RN, will be associated with distinct functional networks which will be abnormal in TRD compared to HCs.	2 years