Using intravenous ketamine to treat severe depression that hasn't responded to other treatments
Central and Peripheral GABA and Glutamate Modulation With Intravenous Ketamine for Treatment-Resistant Depression (G2K): A Randomized, Double-Blind, Placebo-Controlled Study
This study is testing if intravenous ketamine can help adults with severe depression that hasn't improved with other treatments feel better.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Locations | 1 site (Rochester, Minnesota) |
| Trial ID | NCT06668571 on ClinicalTrials.gov |
What this trial studies
This study evaluates the effects of intravenous ketamine on adults with treatment-resistant major depressive disorder (MDD). Participants will be randomly assigned to receive either ketamine or a placebo saline infusion while undergoing MRI scans. The study aims to measure changes in central and peripheral levels of GABA and Glutamate, and how these changes correlate with improvements in depression symptoms assessed by the Montgomery Asberg Depression Rating Scale (MADRS). An optional open-label ketamine infusion will be available after the initial phase of the study.
Who should consider this trial
Good fit: Ideal candidates are adults diagnosed with treatment-resistant major depressive disorder who have failed at least two previous antidepressant treatments.
Not a fit: Patients with primary personality disorders or those with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new option for patients suffering from severe depression that has not responded to traditional therapies.
How similar studies have performed: Other studies have shown promising results with ketamine for treatment-resistant depression, indicating that this approach is gaining traction in the field.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Ability to provide informed consent * Meets diagnostic criteria for major depressive disorder without psychotic features per the SCID DSM-IV-TR * PHQ-9 total score ≥ 15 at screening * Treatment-resistant depression, as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, trial of transcranial magnetic stimulation (TMS) 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: * Inability to speak English * Inability to provide consent or have a legal guardian * Patients with a BMI \> 40 kg/m2. * Personality disorder being the primary diagnosis * Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or active psychotic symptoms * Active post-traumatic stress disorder symptoms based on clinical assessment * Ongoing prescription of \> 2 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment * Medications known to affect glutamate (i.e., Riluzole, Carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, Valproate, Gabapentin, Pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug * Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to administration of study drug * Opioid antagonists (naltrexone, naloxone, nalmefene, methylnaltrexone, buprenorphine and naloxone combination) are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug * CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of study drug and at least 24 hours after last dose of study drug. * Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression * ECT in the past 6 months * 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 * A history of bleeding in the brain * Arteriovenous malformation or a history of aneurysm * Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant (s) within the prior 12 months * Any current substance use disorder (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (\> 1 year) remission * History of traumatic brain injury that resulted in loss of consciousness with brain bleeding * History of tonic-clonic (grand mal) seizures * Developmental delay, intellectual disability, or intellectual disorder * Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months * Minor or Major Neurocognitive disorder * Received ketamine treatment for depression within the prior 2 months * History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered * History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 3 months * Hepatic insufficiency (2.5 X ULN for AST or ALT) within 3 months of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver * Gastroesophageal reflux disease that is poorly managed * A diagnosis of Complex Regional Pain Syndrome (CRPS) * Pregnancy, or nursing * History of claustrophobia with active symptoms that would interfere with the MRI * Any contraindication to MRI safety questionnaire * Poorly controlled hypertension.
Where this trial is running
Rochester, Minnesota
- Mayo Clinic in Rochester — Rochester, Minnesota, United States (Recruiting)
Study contacts
- Principal investigator: Balwinder Singh, M.D., M.S. — Mayo Clinic
- Study coordinator: Nicole Reinicke
- Email: reinicke.nicole@mayo.edu
- Phone: 507-422-1835
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.