The BIO-K Study: A Single-Arm, Open-Label, Biomarker Development Clinical Trial of Ketamine for Non-Psychotic Unipolar Major Depression and Bipolar I or II Depression. (Bio-K)

The purpose of this research study is to find out if the medication known as ketamine can help the symptoms of depression. This drug is approved by the Food and Drug Administration (FDA) but the investigators will use it for a non-FDA approved reason (depression).

Study Overview

• Status: Completed
• Conditions: Major Depression; Unipolar Depression; Bipolar I Disorder; Bipolar II Disorder
• Intervention / Treatment: Drug: Ketamine Hydrochloride

Detailed Description

The investigators will enroll 100 adults with treatment-resistant unipolar or bipolar major depression (TRD) across 7 clinical sites and provide three IV ketamine infusions (0.5 mg/kg, infused over 100 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). The investigators will begin by studying the predictive value of mechanistic target of rapamycin (mTOR) target engagement by ketamine using a white blood cell (WBC) assay for antidepressive response to ketamine (Aim 1); however, samples will be used to develop multiple blood-based biomarkers for ketamine antidepressive effects (Aim 2). The investigators will also examine the effect of combining multiple blood-based biomarkers for predicting antidepressive response to ketamine in adults with TRD (Aim 3).

Baseline WBC markers of impaired cellular energy regulation will be associated with measures of clinical response to ketamine (predictive biomarker). Changes in WBC markers of impaired cellular energy regulation will be associated with clinical response to ketamine (change biomarker).

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Ability to provide informed consent
• Current psychiatric inpatient (voluntary only) or outpatient treatment
• Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder
• Patient Health Questionnaire (PHQ-9) total score > 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
• Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode
• Failed antidepressant or mood stabilizing 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)
• Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria

Exclusion Criteria:

• Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms
• Ongoing prescription of > 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment
• Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression
• Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study
• Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed and illicit) within the past 12 months
• Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine) Note: Persons will be allowed to enroll in this study if their drug or alcohol abuse/dependence is in complete (not partial) and sustained (> 1 year) remission
• History of traumatic brain injury that resulted in loss of consciousness
• Developmental delay, mental retardation, or intellectual disorder
• Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months
• Cognitive disorder (mild and major categories, per DSM-5)
• Prior participation in another study of ketamine for depression within the prior 6 months
• History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression
• History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months
• Significant unstable medical condition
• Hepatic insufficiency (2.5 X upper limit of normal (ULN) for aspartate aminotransferase (AST) or ALT) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver
• Pregnancy, or nursing
• Prisoners
• Involuntary psychiatric hospitalization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; Subjects will receive three IV Ketamine Hydrochloride infusions (0.5 mg/kg, infused over 100 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).	Drug: Ketamine Hydrochloride; Subjects will receive three IV ketamine infusions at 0.5 mg/kg, infused over 100 minutes.; Other Names: Ketalar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Remission of Depression	Total number of subjects with ≤ 9 MADRS score 24 hours post Ketamine infusion #3. The Montgomery Åsberg Depression Scale (MÅDRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed). For this study a score of less than or equal to 9 was considered clinical remission of depression.	24 hours post infusion #3
Suicidal Ideation	Total number of subjects to have a reduction of suicidality, as defined by a 50% reduction on the Beck Scale for Suicidal Ideation (BSS) 24 hours post Ketamine infusion #3. The Beck Scale for Suicidal Ideation consists of 19 items which can be used to evaluate a patient's suicidal intentions. Each of the 19 items is rated on a 0-3 point scale (range 0-38, with higher scores indicating greater suicidal ideations or risk), and includes specific items that assess wish to live, wish to die, desire to make an active suicide attempt, passive suicidal desire, duration of suicidal ideations, frequency of suicidal ideations, and subjective level of control over suicidal actions.	24 hours post infusion #3

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Network of Depression Centers
• Investigators: Principal Investigator: Mark A Frye, MD, Mayo Clinic

Publications and helpful links

General Publications

• Parikh SV, Lopez D, Vande Voort JL, Rico J, Achtyes E, Coryell W, Goddard A, Goes F, Greden JF, Singh B, Kaplin A, Frye MA, Maixner D, Watson B, Drake K, Tarnal V, Riva-Posse P, Bobo WV, Bio-K Study Team. Developing an IV Ketamine Clinic for Treatment-Resistant Depression: a Primer. Psychopharmacol Bull. 2021 Jun 1;51(3):109-124. Review.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): February 12, 2020
• Study Completion (Actual): March 12, 2020

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 16-009737

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No