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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)

Primary Purpose

Major Depression, Bipolar I Disorder, Bipolar II Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ketamine Hydrochloride
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depression

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins Hospital
  • University of Michigan
  • Mayo Clinic
  • University of Cincinnati Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketamine

Arm Description

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).

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 15, 2017
Last Updated
February 23, 2022
Sponsor
Mayo Clinic
Collaborators
National Network of Depression Centers
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1. Study Identification

Unique Protocol Identification Number
NCT03156504
Brief 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.
Acronym
Bio-K
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.
Study Type
Interventional

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
February 12, 2020 (Actual)
Study Completion Date
March 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
National Network of Depression Centers

4. Oversight

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
Data Monitoring Committee
No

5. 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).
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depression, Bipolar I Disorder, Bipolar II Disorder, Unipolar Depression

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ketamine
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Ketamine Hydrochloride
Other Intervention Name(s)
Ketalar
Intervention Description
Subjects will receive three IV ketamine infusions at 0.5 mg/kg, infused over 100 minutes.
Primary Outcome Measure Information:
Title
Clinical Remission of Depression
Description
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.
Time Frame
24 hours post infusion #3
Title
Suicidal Ideation
Description
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.
Time Frame
24 hours post infusion #3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark A Frye, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Cincinnati Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34421148
Citation
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.
Results Reference
derived
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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.

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