The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.
Primary Aim: To identify the best performing condition across a single intravenous infusion of ketamine (KET) 0.1 mg/kg, KET 0.25 mg/kg, KET 0.50 mg/kg) and midazolam (MID) 0.03 mg/kg on Montgomery-Asberg Depression Rating Scale (MADRS) treatment response (at least a 50% improvement in depression from baseline) 7 days after the infusion in up to 72 Veterans with Late-Life Treatment Resistant Depression (LL-TRD) , using a triple blind (patient, rater, anesthesiologist) Bayesian adaptive randomization design. Hypothesis 1: Single KET 0.5 mg/kg infusion is superior to KET 0.1 mg/kg, KET 0.25 mg/kg, and MID 0.03 mg/kg measured by the proportion of participants demonstrating \> 50% reduction on MADRS scores 7 days post-treatment. Secondary Aim: To evaluate the durability of day 7 treatment response across 3 sub-anesthetic doses of a single KET (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and MID (0.03 mg/kg) infusion in veterans with LL-TRD during a 4 week follow-up. Hypothesis 2: a single KET 0.5 mg/kg infusion will be superior to a single infusion of KET 0.1 mg/kg, KET 0.25 mg/kg, and MID 0.03 mg/kg as measured by the proportion of participants demonstrating \> 50% reduction on MADRS scores at 28 days post-infusion. Tertiary Aim: To evaluate the immediate and longer-term safety and tolerability of the most effective KET infusion relative to MID in vets with LL-TRD. Hypothesis 3: KET infusion at the most effective dose will be safe and well tolerated compared to MID, as assessed by psychoactive and general side effect rating scales during and up to 4 weeks post study infusion. Exploratory Aims: 1. To measure the effects of the most effective dose of KET relative to MID on neurocognitive performance. 2. To measure the effects the most effective dose of KET relative to MID on peripheral biomarkers of cellular plasticity and inflammation. 3. To measure the effects the most effective dose of KET relative to MID on resting-state quantitative electroencephalography.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
33
Michael E. DeBakey VA Medical Center, Houston, TX
Houston, Texas, United States
Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores
To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.
Time frame: Day 7 post-infusion
Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS
Patients with a day 7 treatment response (at least a 50% improvement from baseline in Montgomery-Asberg Depression Rating Scale \[MADRS\]) are followed until day 28 post-infusion; day 7 non-responders are not followed. Outcome measure is the percentage of patients who continue to be responder at day 28, and is interpreted as a measure of durability of efficacy.
Time frame: 28 days post-infusion follow-up
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
single 40 min infusion of MID 0.03mg/Kg