Neural and Antidepressant Effects of Propofol

Study Overview
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Brief Summary
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This study will compare the antidepressant effects of propofol at two different doses while measuring potential treatment-related biomarkers.

Detailed Description
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Aim 1: Compare the clinical antidepressant effects of high-dose versus low-dose propofol. Aim 2: Characterize the dose-dependent effects of propofol on brain function and gene expression

Official Title
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Neural and Antidepressant Effects of Propofol

Conditions
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Treatment Resistant Depression

Intervention / Treatment
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* Drug: Propofol
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-55 years Diagnosis of major depressive disorder or bipolar disorder Current moderate-to-severe depressive episode Episode duration more than 2 months and less than 5 years Failure of at least 2 adequate antidepressant medication trials within the past 2 years 16-item Quick Inventory of Depressive Symptomatology, self-rated (QIDS) > 10 24-item Hamilton Depression Rating Scale (HDRS) > 18 Exclusion Criteria: Contraindication to propofol, egg lecithin, soybean oil, or other study drugs Lifetime history of a serious suicide attempt(Gvion and Levi-Belz, 2018) Recent suicidal behavior(past 3 months) Body mass index > 40 kg/m2 Daily use of benzodiazepine, opioid, ACE inhibitor, or ARB medication Symptomatic coronary artery disease or heart failure Poorly controlled hypertension or diabetes Abnormal kidney or liver function Pregnant or breast feeding Traumatic brain injury or significant neurologic signs (past year) Substance use disorder, moderate-to-severe(past 3 months) Obsessive compulsive disorder (past month) Post-traumatic stress disorder (past month) Schizophrenia-spectrum disorder (lifetime) Neurocognitive disorder (past year) Personality disorder as a current focus of treatment ECT within the past 3months Inappropriate for ECT, or poor response to ECT within the past 5 years Incompetent to provide consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants randomized to the high dose will exit the study after treatment. Participants randomized to the low dose who have not experienced response are able to crossover to the high dose.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propofol High Dose<br>high propofol injectable, individually dosed, three times per week | Drug: Propofol<br>* Series of 6 treatments with propofol.<br>* Other names: Diprivan;|
| Experimental: Propofol Low Dose<br>low propofol injectable, individually dosed, three times per week | Drug: Propofol<br>* Series of 6 treatments with propofol. May be able to cross over and receive 6 additional treatments with the high dose of propofol.<br>* Other names: Diprivan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale | 24-item Hamilton Depression Rating Scale, total score Higher values represent more severe depressive symptoms Maximum score, 76; minimum score, 0 Remission defined as total score < 10 Response defined as decrease of total score from baseline of 50% or greater | approximately 17 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Depression Rating Scale | 24-item Hamilton Depression Rating Scale, total score Higher values represent more severe depressive symptoms Maximum score, 76; minimum score, 0 Remission defined as total score < 10 Response defined as decrease of total score from baseline of 50% or greater | approximately 36 days after randomization |