Status:
COMPLETED
MAO-B Occupancy in Depressed Patients
Lead Sponsor:
Centre for Addiction and Mental Health
Conditions:
Major Depressive Disorder
Treatment Resistant Depression
Eligibility:
All Genders
18-80 years
Phase:
NA
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.
Detailed Description
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, ...
Eligibility Criteria
Inclusion
- 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.
Exclusion
- 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
- electroconvulsive therapy or mechanical brain stimulation treatment within the previous 6 months (the effects of these on MAO-B level are unknown but since they could stimulate astrogliosis which could influence MAO-B level these are included as exclusionary)
- 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
- weight over 400lbs and height over 7ft (requirements for fitting in the scanners and hospital gowns)
- the total radiation dose over the currently approved guideline of 20 millisievert (mSv) in a 12-month period. Note: The sievert is a derived unit of ionizing radiation dose in the International System of Units (SI) and is a measure of the health effect of low levels of ionizing radiation on the human body.
- history of undergoing a number of PET scans that, including the number of PET scans under this protocol, will bring the total to more than 8 PET scans/lifetime, exceeding permissible limit for subjects participating in research set by our centre's guidelines
- elevated liver transaminases AST and ALT levels as shown by the laboratory test results
- Additional Requirements for Receiving Tranylcypromine :
- not taking any anesthetics, meperidine (Demerol), anti-asthmatics, anti-hypertensives, dextromethorphan, buspirone, narcotics, codeine (e.g. found in Tylenol), over the counter medication for colds, hay fever, sinus decongestants, eye drops that contain tetrahydrozoline hydrochloride (Visine); SSRI medication including selective reuptake inhibitors (SSRI), amitriptyline, nortriptyline, protriptyline, desipramine, imipramine, doxepin, perphenazine, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, trimipramine; stimulant medication such as: amphetamines, ephedrine, cocaine, methylphenidate, methyldopa, dopamine, levodopa, tryptophan as well as energy-enhancing and weight-reducing preparations for at least 2 weeks
- not taking fluoxetine for at least 6 weeks
- inadequate response to serotonin reuptake inhibitor medication
- inadequate response to medication that raises norepinephrine
- inadequate response to lithium addition to an antidepressant or patient does not want to take lithium due to side effects (such as intention tremor or hypothyroidism risk)
- inadequate response to a medication that raises both serotonin and norepinephrine
- inadequate response to wellbutrin or participant is not able to take wellbutrin due to a contraindication or side effect or participant does not wish to take wellbutrin
- inadequate response to wellbutrin added to a second antidepressant or participant is not able to take wellbutrin due to a contraindication or side effect or participant does not wish to take wellbutrin
- awareness and willingness to follow medication and substance use requirements required of taking tranylcypromine or rasagiline
- Exclusion
- previous hypersensitivity to monoamine oxidase inhibitors
- previous history of hypersensitivity to tyramine
- self report of previous diagnosis of cerebrovascular or cardiovascular disorders
- self report history of recurrent or frequent headaches
- diagnosis of phaeochromocytoma and catecholamine-releasing paragangliomas
- systolic blood pressure not between 91 and 139 mmHg (inclusive)
- diastolic blood pressure not between 51 and 90 mmHg (inclusive)
- a decrease in systolic blood pressure of 20 mm Hg or diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with BP from the sitting position
- use of triptans or tryptamines (e.g. sumatriptan or rizatriptan) in the past 2 weeks.
- 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
- Participants must be antidepressant free for at least 4 weeks prior to scanning (most antidepressants affect monoamines as does duloxetine so a longer period of being medication free is required to be able to separate effect of duloxetine from previous medication).
- Participant must not have a history of non-response to duloxetine at a daily dose of 60mg daily or higher.
Key Trial Info
Start Date :
April 15 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 3 2023
Estimated Enrollment :
50 Patients enrolled
Trial Details
Trial ID
NCT04841798
Start Date
April 15 2021
End Date
July 3 2023
Last Update
July 27 2023
Active Locations (1)
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1
CAMH
Toronto, Ontario, Canada, M5T 1L8