Bipolar Depression, Major Depressive Disorder, Treatment Resistant Depression
Conditions
Brief summary
This is a feasibility study and the goal of this project is to evaluate whether peak ACC GABA and glutamate, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission, Montgomery Asberg Depression Rating Scale (MADRS) total score of \<10, to the anti-glutamatergic antidepressant ketamine. As MRS is expensive, we also aim to study a correlation between change in peripheral metabolites (GABA and glutamate) and central GABA and glutamate levels.
Detailed description
Aims: This feasibility study aims to better understand the neurobiology of major depression and how ketamine may therapeutically impact brain function. This research may provide important insights into the mechanism of ketamine response, thus, potentially increasing the likelihood of successful treatment interventions and decrease the number of ineffective treatments and/or risk for serious side effects. SPECIFIC AIMS: Utilizing novel dynamic sliding-window functional MR spectroscopy (fMRS) and liquid chromatography-mass spectrometry (LCMS), we aim to evaluate the relationship between GABA and glutamate (central-baseline to peak and peripheral-baseline to 24 hours) levels with a change in depression symptoms (baseline to 24 hours), after a single infusion of intravenous (IV) ketamine, in subjects with treatment-resistant depression (TRD).
Interventions
DRUGKetamine
We will enroll 20 adults (aged 18-65 years) with treatment-resistant depression and will provide two i.v. ketamine infusions (0.5 mg/kg, infused over 40 minutes) and measure their depressive symptom responses. Biomarkers will be developed using blood samples from study subjects, taken prior to (predictive biomarkers), and following ketamine treatment (change biomarkers). This will be an open-label feasibility trial.
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in this study, the following will be required: * Ability to provide informed consent; * Current psychiatric inpatient (voluntary only) or outpatient treatment; * Male or female; * Age 18-65 years; * Meets diagnostic criteria for major depressive disorder/bipolar depression without psychotic features per the SCID DSM-IV-TR; * PHQ-9 total score ≥ 15 at screening and at baseline (just prior to first acute phase ketamine infusion); * Treatment-resistant depression (TRD), as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT) or an acute series of Transcranial magnetic stimulation (TMS); * Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.
Exclusion criteria
Based on ketamine's known difficulties with the induction of perceptual/psychomimetic symptoms, the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate percent change in the anterior cingulate cortex (ACC) GABA and Glutamate (baseline to peak) during a 40-minute IV ketamine infusion and remission (MADRS ≤9) at 24 hour | 24 hour | Percent change in central metabolites and association with remission |
| To evaluate a correlation between percent change in ACC GABA and Glutamate/Glx levels (baseline to peak) with a change in MADRS (baseline to 24 hours). | 24 hour | Change in central metabolite and association with change in depression scores |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare the percent change in peripheral GABA/Glutamate levels between remitters and non-remitters | 24 hour | Change in peripheral metabolites and association with remission |
| To evaluate the correlation between percent change in peripheral GABA and glutamate levels with a change in MADRS scores. | 24 hour | Change in peripheral metabolites and association with change in depression (MADRS) scores |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBalwinder Singh, MD, MS
Mayo Clinic
Outcome results
None listed