MAO-B Occupancy in Depressed Patients

NCT04841798 | Completed DMC

• 1 other identifier: REB#094/2018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study is looking at assessing monoamine oxidase B (MAO-B) occupancy in depressed patients before and after medication treatment using positron emission tomography (PET) scan.

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Outcome Measures

Primary Outcomes (2)

• MAO-B occupancy of tranylcypromine at standard treating dose

  MAO-B Occupancy is an overall occupancy measure that is intended to be derived from Lassen Plot. The Lassen Plot will include MAO-B total distribution volume (VT) values before and after treatment in regions that optimize the plot. It is expected that these will include prefrontal cortex, anterior cingulate cortex, dorsal putamen, ventral striatum, hippocampus, and cerebellum. To quantify the regional monoamine oxidase B (MAO-B) occupancy we use a measure called the total distribution volume (VT) an index of MAO-B density. The percent change, termed occupancy can range from 0% to 100%.

  3 years

• MAO-B occupancy of rasagiline at standard treating dose

  MAO-B Occupancy is an overall occupancy measure that is intended to be derived from Lassen Plot. The Lassen Plot will include MAO-B total distribution volume (VT) values before and after treatment in regions that optimize the plot. It is expected that these will include prefrontal cortex, anterior cingulate cortex, dorsal putamen, ventral striatum, hippocampus, and cerebellum. To quantify the regional monoamine oxidase B (MAO-B) occupancy we use a measure called the total distribution volume (VT) an index of MAO-B density. The percent change, termed occupancy can range from 0% to 100%.

  3 years

Secondary Outcomes (2)

• Rasagiline effect on MAO-B distribution volume (VT) in the prefrontal cortex

  3 years

• Rasagiline effect on MAO-B distribution volume (VT) and cognition in MDE post COVID-19

  3 years

Study Arms (3)

Duloxetine

OTHER

Assessment of MAO-B distribution volume in the prefrontal cortex before and after duloxetine at 60 mg daily.

Other: [11C]SL25.1188 PET radiotracer

Rasagiline

OTHER

Assessment of regional MAO-B distribution volume before and after rasagiline at 1.0 mg daily.

Other: [11C]SL25.1188 PET radiotracer

Tranylcypromine

OTHER

Assessment of regional MAO-B distribution volume before and after tranylcypromine at 30 to 60 mg daily.

Other: [11C]SL25.1188 PET radiotracer

Interventions

[11C]SL25.1188 PET radiotracer OTHER

Monoamine oxidase B (MAO-B) occupancy before and after medication treatment using \[11C\]SL25.1188 PET

Duloxetine; Rasagiline; Tranylcypromine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age 18 to 80
• DSM-5 diagnosis of current MDE and MDD verified by the research version of SCID for DSM-5
• early onset type MDD with first MDE prior to age 40
• score greater than or equal to 17 on the 17 item Hamilton Depression Rating Scale (HDRS)28
• antidepressant free for at least 2 weeks (by self report)
• worsening of MDE symptoms or new onset MDE symptoms after COVID-19 may receive rasagiline and complete all procedures except the second \[11-C\]SL25.1188 PET scan - participants with this criteria will be enrolled in the alternative criteria that is similar to the general criteria except for the second PET scan.

You may not qualify if:

• history of psychotic symptoms
• history of antisocial or borderline personality disorders (screened with the Structured Clinical Interview for Personality Disorders (SCID) for Diagnostic and Statistical Manual-5 (DSM-5) (unless occuring after COVID)
• history of neurodegenerative illness
• cigarette smoking for the past 6 months (there are reports that cigarette smoking lowers monoamine oxidase B 31, 32.)
• currently abusing street drugs
• current alcohol use disorder
• diagnosis of liver or kidney disease
• positive for hepatic dysfunction as measured by aspartate transaminase (AST) and alanine transaminase (ALT) tests
• diagnosis of cardiovascular disease such as hypertension/hypotension, angina or tachycardia
• positive pregnancy test (in our Centre women up to 65 years of age are given a urine pregnancy test prior to every PET scan)
• currently breastfeeding
• recent use of MAO-B inhibitor treatments (within the previous 4 weeks)
• disorders of coagulation, blood or ongoing use of anticoagulant medication
• presence of metal objects or implanted electrical devices in the body that would preclude MRI scanning
• claustrophobia

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead

Study Sites (1)

CAMH

Toronto, Ontario, M5T 1L8, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Jeffrey H Meyer, MD, PhD

  CAMH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 12, 2021
• Study Start: April 15, 2021
• Primary Completion: July 1, 2023
• Study Completion: July 3, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

CA (1)