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)

• ClinicalTrials.gov Identifier: NCT03156504
• Recruitment Status: Enrolling by invitation
• First Posted: May 17, 2017
• Last Update Posted: March 21, 2019
• Sponsor: Mayo Clinic
• Collaborator: National Network of Depression Centers
• Information provided by (Responsible Party): Jennifer L. Vande Voort, M.D., Mayo Clinic

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Major Depression; Bipolar I Disorder; Bipolar II Disorder; Unipolar Depression	Drug: Ketamine Hydrochloride	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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.
• Actual Study Start Date: June 1, 2017
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: January 2020

Arms and Interventions

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 Name: Ketalar

Outcome Measures

Primary Outcome Measures :

1. Change in MÅDRS total score. [ Time Frame: Baseline, approximately 1 week ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Maryland

Johns Hopkins Hospital

Baltimore, Maryland, United States, 21287

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Ohio

University of Cincinnati Medical Center

Cincinnati, Ohio, United States, 45219

Sponsors and Collaborators

Mayo Clinic

National Network of Depression Centers

Investigators

• Principal Investigator: Mark A Frye, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Jennifer L. Vande Voort, M.D., Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03156504 History of Changes
• Other Study ID Numbers: 16-009737
• First Posted: May 17, 2017
• Last Update Posted: March 21, 2019
• Last Verified: March 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Disease; Depression; Depressive Disorder; Depressive Disorder, Major; Pathologic Processes; Behavioral Symptoms; Mood Disorders; Mental Disorders; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action