Characterizing Synaptic Density in Treatment Resistant Depression
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age25-65
SponsorUnity Health Toronto
About this trial
The purpose of this study is to better understand how certain brain systems work in people with depression, especially in those whose symptoms have not improved with antidepressant treatments. The investigators are particularly interested in synaptic density, which helps to understand how different parts of the brain communicate with one another. Synaptic density levels have implications on overall brain function and cognition. By comparing brain function in people with treatment-resistant depression, people with treatment-responsive depression, and healthy controls, investigators hope to better understand why some individuals do not respond to antidepressants. This research may help guide the development of more effective treatments in the future.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
DSM-5 criteria for a Major Depressive Episode (MDE) within a MDD, confirmed through MINI diagnosis (Sheehan et al, 2015)
Age between 25 and 65 years
Hamilton Depression Rating Scale - 17 item (HRSD-17; Hamilton, 1960) > 14 (moderate to severe symptoms)
Free of psychotropic medications (with the exception of SSRIs or SNRIs) for at least 5 half-lives before PET scanning per investigator discretion, after which an insignificant amount of drug is circulating through the body and accessing the brain. This determination will be based on self-report from the participant of when their last dose was. Use of benzodiazepines (except for diazepam) or sedative hypnotics (e.g. zopiclone) is allowable, but the last dose must be at least 72 hours prior to scanning.
Disqualifiers
Pregnancy/lactation
Medical condition requiring immediate investigation or treatment
Recent (< 6 months)/current history of drug abuse/dependence
Lifetime history of psychosis, other Axis I comorbidities are allowable
Trial population
Participants will be recruited from clinics at St. Michael's Hospital and the Centre for Addiction and Mental Health as well as from research programs at the two sites, which have ongoing MDD clinical trials where patients are required to be unmedicated prior to initiating treatment.
Trial design
Design model
Case-control
Time perspective
Cross-sectional
Treatments tested in this trial
PET scans
Diagnostic testPET scans and PHNO scans
Treatment groups
45 Participants
are divided into 3 treatment groupsGroup A: Treatment Resistant Depression1 intervention
Group B: Major Depressive Disorder1 intervention
Group C: Healthy Control1 intervention
Trial outcomes
Primary outcomes
1
Synaptic Density
Synaptic density represents a promising biomarker for TRD, as it provides a direct index of neural circuit integrity and synaptic architecture (Appelbaum et al, 2022; Serano et al, 2022). Interventions shown to be effective in treatment-resistant populations, including rapid-acting antidepressants and neuromodulatory approaches, have been proposed to engage in synaptic plasticity-related mechanisms (Duman et al, 2016). As such, synaptic density measured using SV2A PET may offer insight into circuit-level abnormalities relevant to depression severity and treatment resistance, therefore offering a mechanistically informed approach for characterizing the biological correlates of TRD and supports its use in PET-based investigations of this population
Time frame
3 yearsSponsors and contacts
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Unity Health Toronto
Lead sponsor
Centre for Addiction and Mental Health
Collaborator
Source ClinicalTrials.gov