An interventional study of [11C]SL25.1188 PET radiotracer in Major Depressive Disorder and Treatment Resistant Depression, sponsored by Centre for Addiction and Mental Health. Completed at 1 site in Canada. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2023-07-27.
Sponsored by Centre for Addiction and Mental Health · Not applicable, Interventional, and Other
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.
BACKGROUND
1.1 Problem of Treatment Resistant Depression and a Proposed Solution
Problem of Major Depressive Disorder: Major depressive disorder (MDD) known to the layperson as clinical depression, is an illness composed of repeated major depressive episodes of variable length and persistence (MDE).
MDD is the leading cause of death and disability in moderate to high income countries. MDD is common with 5% of adults in the midst of a major depressive episode (MDE) and the lifetime prevalence of MDD is 10 to 20%. MDD is also often treatment resistant, with 50% of people having inadequate responses. Plausible Mechanism of Treatment Resistance: It is generally believed that there are multiple underlying pathologies in MDD and the mismatch of treatment to pathology results in treatment resistance. Hence it is important to determine whether common brain pathologies are targeted by common treatments like serotonin and norepinephrine reuptake inhibitors, and to establish the degree to which alternative treatments might better target such brain pathologies. Then with this information matching of treatment to identified disease pathologies can be optimized.
STUDY OBJECTIVES
Overview Rationale for Objectives The abnormal elevation in MAO-B level in MDE of MDD was most prominent in the prefrontal cortex, hence the investigators prioritize this region in our objectives. As detailed in the introduction, the investigators will assess MAO-B occupancy of tranylcypromine because it is a MAO-B inhibitor, albeit non-selective, that is approved in Canada for clinical use to treat MDD. The investigators assess rasagiline as a selective MAO-B inhibitor that does not require stringent dietary restriction of tyramine at the 1mg dose, which is approved for Parkinson's Disease in Canada and has potential to be purposed to treat MDD. The investigators will also include assessment of MAO-B VT before and after duloxetine to verify the widespread assumption that the commonly prescribed medications that inhibit the reuptake of serotonin and norepinephrine, do not affect MAO-B level.
Primary Objectives
To measure MAO-B occupancy of rasagiline at 1mg total daily, a dose not requiring stringent tyramine dietary restriction in the prefrontal cortex.
Secondary Objective
The methods to quantitate more exact occupancy inherently require some MAO-B occupancy to occur, so in the case of objective 3, the related measure of change in MAO-B VT will be assessed. In addition, investigators will evaluate MAO-B occupancy of the interventions listed in objectives 1 and 2 within other brain regions with either reasonably high MAO-B density or whose dysfunction is implicated in the pathophysiology of MDD, including the anterior cingulate cortex, ventral striatum, dorsal striatum, thalamus, hippocampus, and midbrain. With respect to objective 4, it is expected that participants with more elevated MAO-B VT will have a greater response to rasagiline.
4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.
This study's enrollment of 50 is below the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.
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Inclusion Criteria:
Exclusion Criteria:
Additional Requirements for Receiving Tranylcypromine :
Exclusion
Additional Requirements for Taking Rasagiline
Inclusion
● Participant does not wish to take tranylcypromine due to concerns regarding side effects or the strict dietary restrictions of reduced tyramine intake required for taking tranylcypromine.
Additional Requirements for Taking Duloxetine:
Inclusion
Assessment of MAO-B distribution volume in the prefrontal cortex before and after duloxetine at 60 mg daily.
Other: [11C]SL25.1188 PET radiotracer
Assessment of regional MAO-B distribution volume before and after rasagiline at 1.0 mg daily.
Other: [11C]SL25.1188 PET radiotracer
Assessment of regional MAO-B distribution volume before and after tranylcypromine at 30 to 60 mg daily.
Other: [11C]SL25.1188 PET radiotracer
Monoamine oxidase B (MAO-B) occupancy before and after medication treatment using \[11C\]SL25.1188 PET
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%.
Time frame: 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%.
Time frame: 3 years
Rasagiline effect on MAO-B distribution volume (VT) in the prefrontal cortex
Rasagiline effect on MAO-B distribution volume (VT) in the prefrontal cortex. 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%.
Time frame: 3 years
Rasagiline effect on MAO-B distribution volume (VT) and cognition in MDE post COVID-19
Rasagiline effect on the total Hamilton Depression Rating Scale (HDRS). The Hamilton Rating Scale for Depression (HRSD) scoring is based on the 17-item scale. Scores of 0-7 are considered as being normal, 8-13 higher than normal, 14-16 modestly clinical, 17-19 mild depression, 20-23 moderate depression and scores 24 or greater are considered severe depression. The maximum sore being 52. Higher scores represent worse outcomes.
Time frame: 3 years
This study is completed, as verified in Jul 2023. You cannot join it, but the record below documents what was studied.
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Centre for Addiction and Mental Health