The UTHealth Ketamine Project

Study Overview
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Brief Summary
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The primary objective of this study is to determine the effectiveness of serial infusions of intravenous (IV) ketamine in adults with treatment resistant depression (TRD).

Detailed Description
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Thus, in the current study we want to naturalistically explore the antidepressant effects of serial slow IV infusions (40 minutes) of ketamine at a dose of 0.5 mg/kg, over a treatment period of 8 weeks in an academic psychiatric hospital. This is a minimal sedation treatment. The primary outcome measure of this study will be remission estimated based on the severity of depressive scores. After the 8 weeks of treatment, there will be a four week observational period. During the observational period, participants will receive treatment as usual and will be contacted over the phone for follow-up questions regarding their overall health status, mood and clinical state. They will also complete a neurocognitive task at the end of the 4 week observational period

Official Title
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A Naturalistic Study of Serial Infusion of Low-dose Ketamine for Treatment Resistant Depressive Disorders in an Academic Psychiatric Hospital: The UTHealth Ketamine Project

Conditions
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Treatment Resistant Depression, Major Depressive Disorder, Bipolar Disorder

Intervention / Treatment
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* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with major depressive disorder (MDD) or bipolar disorder (BD) patients with documented treatment resistant disorder (TRD) (according to Diagnostic Statistical Manual (DSM-IV TR)), and who have failed (defined as patient does not reach remission within the 8 week trial of an antidepressant or combination at a therapeutic dose) of at least two trials of first line evidence-based treatments and/or electroconvulsive therapy (ECT) Exclusion Criteria: Being younger than 18 of age or older than 65. Diagnosed with intellectual disability, e.g. mental retardation (MR), neurodegenerative diseases, e.g. early-onset neurocognitive disturbances such as frontotemporal dementia (FTD) or behavioral disorders, e.g. adult onset Attention Deficit Hyperactivity Disorder (ADHD). Diagnosed with bipolar disorder not otherwise specified (BD-NOS) or rapid cycling BD Diagnosed with personality disorders (PD). Previously or currently diagnosed with psychosis (schizoaffective disorder - SAD) or schizophrenia - SCZ). Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., obstructive sleep apnea requiring Continuous Positive Airway Pressure (CPAP), liver insufficiency, kidney insufficiency, cardiovascular problems, systemic infections, cancer, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases); history of any brain diseases, including seizures, stroke, meningitis, encephalitis, dementia, degenerative brain diseases, and head injury with loss of consciousness for any period of time. Diagnosed specifically with a cardiovascular disorders such as Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) or suffering from Chronic Obstructive Pulmonary Disease (COPD) or asthma. Suffering from uncontrolled hypertension or diastolic BP over 100. Cardiac clearance prior to enrolling in the study/medical records from physician will be required per patient's primary care physician (PCP). Patients with increased risk of laryngospasm, active upper respiratory infections, respiratory depression, increased intracranial pressure, hyperthyroidism, or porphyria. Current substance abuse or dependence. Only patients who achieved stable, full remission for at least 6 months will be included. Pregnancy or Breast feeding. All female in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study. Unable to understand the design and requirements of the study Unable to sign the informed consent for any reason An assigned responsible adult has provided assent to assist in patient's study participation. The responsible adult agrees to be present at each study appointment as well as provide transportation to study appointments for the patient.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ketamine<br> | Drug: Ketamine<br>* Ketamine will be infused (slow IV infusions of ketamine (0.5 mg/kg) over 40 minutes) twice weekly over a period of 4 weeks and weekly for the following 4 weeks of the study treatment period (8 weeks total).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Will be Measured Through Number of Adverse Events |  | Baseline through week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Treatment Will be Measured on of Clinical Global Impressions (CGI) |  | Baseline, week 8, week 12 | 
| Severity of Depressive Symptoms as Assessed by the PHQ-9 | The Patient Health Questionnaire (PHQ)-9 is the 9-item depression module from the full Patient Health Questionnaire (PHQ) PHQ-9 total score ranges from 0 to 27 (each of the 9 items can be scored from 0 (not at all) to 3 (nearly every day)), and a higher score indicates greater depression. | Baseline, week 8, week 12 |