Major DepressionPhase 4Bio-KNCT03156504
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.
A Phase 4 study testing Ketamine Hydrochloride in people with Major Depression and Bipolar I Disorder, run by Mayo Clinic at 4 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depression, Bipolar I Disorder, Bipolar II Disorder
- What is being tested?
- Ketamine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jun 2017to 12 Mar 2020
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 18Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Michigan
Ann Arbor, Michigan, 48109
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
Mayo Clinic
Rochester, Minnesota, 55905
About this study
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).
Read the 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).
- Being tested
- Ketamine Hydrochloride
- Medical subject headings
- Depressive Disorder, Major, Bipolar Disorder, Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine HydrochlorideDrug
Also called Ketalar
Subjects will receive three IV ketamine infusions at 0.5 mg/kg, infused over 100 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | 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). Receives: Drug: Ketamine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 hours post infusion #3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2017
- Study start1 Jun 2017
- Primary completion12 Feb 2020
- Study completion12 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Network of Depression Centers
- Responsible party
- Principal investigator, Jennifer L. Vande Voort, M.D., Mayo Clinic
- Investigators
- Mark A Frye, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03156504
- Sponsor's protocol ID
- 16-009737
- Acronym
- Bio-K
- Status last verified
- Feb 2022
- First submitted
- 15 May 2017
- Last updated
- 15 Mar 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Singh B, MahmoudianDehkordi S, Vande Voort JL, Parikh SV, Achtyes ED, Goes FS, Bobo WV, Greden JF, Scaini G, Tye S, Frye MA, Kaddurah-Daouk R. Metabolomic correlates of intravenous racemic ketamine in treatment-resistant major depressive disorder: the Bio-K/NNDC multicenter trial. World J Biol Psychiatry. 2026 Sep 6:1-15. doi: 10.1080/15622975.2026.2724510. Online ahead of print.
PubMed 42702010Singh B, Parikh SV, Voort JLV, Pazdernik VK, Achtyes ED, Goes FS, Yocum AK, Nykamp L, Becerra A, Smart L, Greden JF, Bobo WV, Frye MA, Burdick KE, Ryan KA. Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial. Psychiatry Res. 2024 May;335:115829. doi: 10.1016/j.psychres.2024.115829. Epub 2024 Feb 28.
PubMed 38479192Parikh SV, Vande Voort JL, Yocum AK, Achtyes E, Goes FS, Nykamp L, Singh B, Lopez-Vives D, Sera CE, Maixner D, Tarnal V, Severe J, Bartek S, Tye SJ, Rico J, Stoppel CJ, Becerra A, Smart L, Miller CR, Frye MA, Greden JF, Bobo WV. Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression. J Affect Disord. 2024 Mar 1;348:143-151. doi: 10.1016/j.jad.2023.12.033. Epub 2023 Dec 22.
PubMed 38142892
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03156504
- Acronym / sponsor ID
- Bio-K / 16-009737
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Network of Depression Centers
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 12 Feb 2020 (actual)
- Study completion
- 12 Mar 2020 (actual)
- First posted
- 17 May 2017 (actual)
- Results
- Posted 15 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: Ketamine HydrochlorideSubjects 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketamine HydrochlorideAlso: KetalarSubjects will receive three IV ketamine infusions at 0.5 mg/kg, infused over 100 minutes. | Drug | Ketamine |
Primary outcome
Clinical Remission of Depression
Time frame: 24 hours post infusion #3
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
Time frame: 24 hours post infusion #3
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42702010Singh B, MahmoudianDehkordi S, Vande Voort JL, Parikh SV, Achtyes ED, Goes FS, Bobo WV, Greden JF, Scaini G, Tye S, Frye MA, Kaddurah-Daouk R. Metabolomic correlates of intravenous racemic ketamine in treatment-resistant major depressive disorder: the Bio-K/NNDC multicenter trial. World J Biol Psychiatry. 2026 Sep 6:1-15. doi: 10.1080/15622975.2026.2724510. Online ahead of print.
- Derived from this study: PubMed 38479192Singh B, Parikh SV, Voort JLV, Pazdernik VK, Achtyes ED, Goes FS, Yocum AK, Nykamp L, Becerra A, Smart L, Greden JF, Bobo WV, Frye MA, Burdick KE, Ryan KA. Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial. Psychiatry Res. 2024 May;335:115829. doi: 10.1016/j.psychres.2024.115829. Epub 2024 Feb 28.
- Derived from this study: PubMed 38142892Parikh SV, Vande Voort JL, Yocum AK, Achtyes E, Goes FS, Nykamp L, Singh B, Lopez-Vives D, Sera CE, Maixner D, Tarnal V, Severe J, Bartek S, Tye SJ, Rico J, Stoppel CJ, Becerra A, Smart L, Miller CR, Frye MA, Greden JF, Bobo WV. Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression. J Affect Disord. 2024 Mar 1;348:143-151. doi: 10.1016/j.jad.2023.12.033. Epub 2023 Dec 22.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark A Frye, MD principal investigator
Mayo Clinic
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine Hydrochloride in people with Major Depression and Bipolar I Disorder, run by Mayo Clinic at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Remission of Depression (time frame: 24 hours post infusion #3). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03156504, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2022.