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.
Single-arm, Phase IV biomarker study (n=75) of three IV ketamine infusions (0.5 mg/kg over 100 minutes) for adults with treatment-resistant unipolar or bipolar depression to develop blood-based predictive and change biomarkers.
Detailed Description
This single-group study administers three intravenous ketamine hydrochloride infusions (0.5 mg/kg, each infused over 100 minutes) to adults with treatment-resistant major depression or bipolar depression and measures depressive symptom response.
Blood samples collected before and after treatment will be used to develop and test predictive and change biomarkers, including assessment of mTOR target engagement in white blood cells and composite blood-based markers of ketamine antidepressive effects.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
Ketamine
experimentalThree IV infusions of ketamine hydrochloride (0.5 mg/kg over 100 minutes) with biomarker development from blood samples.
Interventions
- Ketamine0.5 mg/kgvia IV• three sessions• 3 doses total
Each infusion given over 100 minutes; blood samples before and after dosing for biomarker development.
Participants
Inclusion Criteria
- Ability to provide informed consent
- Current psychiatric inpatient (voluntary only) or outpatient treatment
- Meets 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, defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode
- Failed treatments can include pharmacotherapy at adequate dose for ≥8 weeks or an acute series of ≥6 administrations of ECT
- Ability to pass a comprehension assessment 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 daily, or morning dosing of any benzodiazepine at time of assessment
- Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as acute or maintenance depression treatment
- Any active or unstable medical condition judged by study psychiatrist to confer excessive medical risk
- Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed or illicit) within past 12 months
- Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine); persons in complete remission >1 year allowed
- History of traumatic brain injury with loss of consciousness
- Developmental delay, intellectual disability, or mental retardation
- Clinical or self-reported delirium, encephalopathy, or related diagnosis within prior 12 months
- Cognitive disorder (mild or major, per DSM-5)
- Prior participation in another ketamine study for depression within prior 6 months
- History of poor antidepressant response to or poor tolerability of ketamine when previously administered for depression
- History of hypothyroidism unless on stable thyroid medication and asymptomatic for 6 months
- Significant unstable medical condition
- Hepatic insufficiency (AST or ALT ≥2.5× ULN within 1 year), past liver transplant, or clinical cirrhosis
- Pregnancy or nursing
- Prisoners
- Involuntary psychiatric hospitalization
Study Details
- StatusCompleted
- PhasePhase IV
- Typeinterventional
- DesignNon-randomized
- Target Enrollment75 participants
- TimelineStart: 2017-01-06End: 2022-03-12
- Compound
- Topic