Ketamine for Bipolar Disorder (KET-BD Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Joshua Rosenblat
Stay on your current meds
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?Growing evidence has supported rapid and robust antidepressant effects with subanesthetic doses of intravenous (IV) ketamine for treatment resistant depression (TRD). However, no completed or ongoing randomized control trials (RCTs) have evaluated the effects of repeated doses of IV ketamine for a homogenous sample of patients with treatment-resistant bipolar disorder (TRBD). The primary research goal is to determine the acute antidepressant efficacy, safety and tolerability of four repeated sub-anesthetic doses of IV ketamine in moderate to severe TRBD. Secondary aims include evaluating effects of IV ketamine on suicidal ideations, quality of life, function and duration of effects. Herein, a two-site (University Health Network and Ontario Shores Centre for Mental Health Sciences), phase II, double-blinded, midazolam-controlled, two-week RCT evaluating the efficacy, safety and tolerability of four flexibly-dosed adjunctive ketamine infusions (0.5-0.75mg/kg infused over 40 minutes) for acute treatment of moderate to severe TRBD (type I \& II) is proposed. The primary outcome will be Montgomery-Åsberg Depression Rating Scale (MADRS) scores, determining the between group difference in change from baseline to day 14, using analysis of covariance (ANCOVA), with 14-day MADRS as the outcome and baseline MADRS and stratification variables (sex, bipolar type) as covariates. Secondary outcomes include evaluating response and remission rates, safety, tolerability (including treatment-emergent mania), and effects on suicidality, anxiety, quality of life, function and the duration of effects (to day 28).
Will I have to stop taking my current medications?
You can continue taking your current mood stabilizer or antipsychotic medication as long as it hasn't changed in the last month. However, you must stop using certain medications like benzodiazepines, stimulants, and cannabis during the trial.
How is ketamine different from other drugs for bipolar disorder?
Ketamine is unique for bipolar disorder because it acts rapidly to reduce depressive symptoms and suicidal thoughts, unlike traditional treatments that may take weeks to show effects. It is administered intravenously (through a vein), which allows for quick action, and is often used when other treatments have failed.
1891011Is ketamine safe for use in humans?
Research shows that ketamine, often used with midazolam, is generally safe for sedation and pain management in children, with few side effects that require minor or no intervention.
23459What data supports the effectiveness of the drug Ketamine Hydrochloride, Ketalar, Special K, Midazolam Hydrochloride, Midazolam, Versed for treating Bipolar Disorder?
Research shows that ketamine, when used with midazolam, is effective in improving mood disorders, with a significant effect size observed in studies. Additionally, the combination of ketamine and midazolam has been shown to improve cooperation and behavior in children during medical procedures, suggesting potential benefits in managing symptoms.
267911Eligibility Criteria
This trial is for adults aged 21-65 with moderate to severe bipolar depression that hasn't improved after trying at least two standard treatments. Participants must be on a stable medication regimen and not currently experiencing mania or psychosis. Pregnant or breastfeeding women, those with certain medical conditions, or recent substance abuse are excluded.Inclusion Criteria
My bipolar depression hasn't improved after trying two or more recommended treatments.
I have been diagnosed with Bipolar I or II and am currently having a major depressive episode without experiencing psychosis.
I am between 21 and 65 years old.
Exclusion Criteria
I do not have allergies or health conditions that make ketamine or midazolam unsafe for me.
I am not using ketamine, benzodiazepines, MAOIs, stimulants, or any form of cannabis.
I am currently experiencing symptoms of mania or bipolar disorder.
I have not had major neurological issues or strokes in the last year.
Participant Groups
The study tests if four doses of IV ketamine can safely reduce depression symptoms in treatment-resistant bipolar disorder (TRBD) patients compared to midazolam, a control drug. It's a phase II trial measuring the change in depression severity over two weeks and monitoring quality of life and suicidal thoughts.
2Treatment groups
Experimental Treatment
Active Control
Group I: KetamineExperimental Treatment1 Intervention
Four infusions of ketamine will be administered over two weeks. The first two infusions will be dosed at 0.5mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.5 mg/kg to 0.75 mg/kg, depending on clinical response to first two infusions.
Group II: MidazolamActive Control1 Intervention
Four infusions of midazolam will be administered over two weeks. The first two infusions will be dosed at 0.02mg/kg over a period of 40 minutes. For infusions 3 and 4, patients will be flexibly dosed between 0.02 mg/kg to 0.03 mg/kg, depending on clinical response to first two infusions.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Ontario Shores Centre for Mental Health SciencesWhitby, Canada
Toronto General HospitalToronto, Canada
Toronto Western HospitalToronto, Canada
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Who is running the clinical trial?
Joshua RosenblatLead Sponsor
University Health Network, TorontoLead Sponsor
References
[Chemical compatibility of ketamine and midazolam in infusion solutions]. [2013]The chemical compatibilities of intravenous (i.v.) solutions containing ketamine and midazolam were investigated by UV/VIS spectroscopy, IR spectroscopy, and high-performance liquid chromatography (HPLC). The isotonic solutions used were NaCl 0.9%, fructose 5%, and glucose 5%. The concentrations of additives were 500 mg ketamine and 45 mg midazolam per liter i.v. solution. Comparison of the UV/VIS and IR spectroscopic measurements with spectra from the literature demonstrated, that the substances were pure, e.g. without larger impurities. The HPLC measurements were performed immediately after preparation of the solution and repeated after 6, 25, 50, 75 and 97 h. It was shown that there was no concentration decrease of ketamine and midazolam in the i.v. solutions within an experimental error of 1.5% and within 100 h. Reactions in the i.v. solutions with smaller than 1.5% conversion can not be excluded. We recommend that the prepared i.v. solution be used within 24 h.
Sedation for pediatric procedures, using ketamine and midazolam, in a primarily adult intensive care unit: a retrospective evaluation. [2019]To evaluate the effectiveness and safety of pediatric procedures performed by adult critical care practitioners, using the combination of ketamine and midazolam for anesthesia and sedation.
Use of intravenous ketamine-midazolam association for pain procedures in children with cancer. A prospective study. [2022]We evaluated the safety and efficacy of midazolam-ketamine association to control pain induced by diagnostic procedures in paediatric oncology patients. 226 procedures were carried out in 92 patients aged three days to 18 years. Drugs were given i.v. by an anaesthesiologist. Midazolam dose was 25 microg.kg-1 and ketamine 0. 5 to 2 mg.kg-1, depending on number and invasiveness of procedures. The mean dose of ketamine was 1 mg.kg-1. Mean duration of sedation was ten min. No complication was observed and analgesia was considered satisfactory in 89 out of 92 patients. These results indicate that midazolam-ketamine is a safe and effective association in pain management for paediatric oncology patients and efficiently induces brief unconscious sedation with analgesia.
Inter- and intraindividual variability in ketamine dosage in repetitive invasive procedures in children with malignancies. [2013]Midazolam/ketamine sedation has been used successfully in children undergoing painful invasive procedures. The authors prospectively assessed inter- and intra-individual variability in ketamine dosage for sedation in repetitive invasive procedures in children with malignancies. A total of 92 invasive procedures (58 lumbar punctures, 34 bone marrow biopsies; range: 2-9 procedures/patient) were performed on 25 children (median age: 12 years). Intravenous sedation consisted of 0.1 mg midazolam/kg and 0.5-1.0 mg ketamine/kg. Incremental dosages of ketamine (0.33 mg/kg) were given if necessary to achieve or maintain deep sedation. Primary outcome measure was the inter- and intraindividual ketamine dosage required to achieve adequate sedation; secondary outcome measures were the number of procedures with adequate sedation (Ramsay score of > 4), the number of adverse side effects, and the need for therapeutic interventions. All 92 invasive procedures were completed with satisfactory sedation levels in 88 procedures (95.7%). There was a great inter- and intraindividual variability in ketamine dosage required to achieve or maintain adequate sedation. In 12% of procedures side effects were seen, which required no or only minor interventions. Due to great inter- and intraindividual differences, ketamine dosage should be titrated toward the desired level of sedation. Thus, ketamine can be adjusted to the individual's need while achieving adequate sedation.
Midazolam or ketamine for procedural sedation of children in the emergency department. [2018]A short cut review was carried out to establish whether ketamine or midazolam is superior at providing safe and effective conscious sedation in children in the emergency department. A total of 203 papers were found using the reported searches, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are summarised in table 1. It is concluded that midazolam and ketamine have similar efficacy and safety profiles but that ketamine is preferred by parents and physicians.
Combined oral midazolam-ketamine better than midazolam alone for sedation of young children: a randomized controlled trial. [2022]BACKGROUND. There is a lack of clinical trials on paediatric dental sedation. AIM. We investigated whether young children's behaviour improves during dental treatment with oral ketamine/midazolam compared with midazolam alone or no sedation. DESIGN. Healthy children under 36 months of age, presenting early childhood caries were randomly assigned to receive protective stabilization plus: combined oral midazolam (0.5 mg/kg) and ketamine (3 mg/kg) (MK), or oral midazolam (1.0 mg/kg) (MS), or no sedative (PS). One observer scored children's behaviour using the Ohio State University Behavior Rating Scale (OSUBRS) at determined points in a dental exam (no sedative) and treatment session. Data were analysed using nonparametric bivariate tests. RESULTS. Forty-one children were included. In the dental exam session, the sum of OSUBRS scores was similar for the three groups (P = 0.81). In the treatment session, the MK produced more cooperative behaviour than MS and PS (P = 0.01), longer sessions (P = 0.04), and a pattern of homogeneous OSUBRS scores from the reception area (before sedative administration) to the end of the session (P = 0.06). No immediate and post-discharge side effects were observed in groups MK and MS. CONCLUSIONS. The combination of oral midazolam and ketamine is efficacious for guiding the behaviour of children under 3 years old.
A double-blind, randomised, placebo-controlled trial of oral midazolam plus oral ketamine for sedation of children during laceration repair. [2022]To compare the efficacy of oral midazolam alone with a combination of oral midazolam and ketamine in children requiring laceration repair.
Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial. [2022]To evaluate feasibility and effects of a sub-anesthetic infusion dose of ketamine versus midazolam on suicidal ideation in bipolar depression. Neurocognitive, blood and saliva biomarkers were explored.
Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant. [2021]The goal of this study was to infer the effectiveness of midazolam as a comparator in preserving the blind in ketamine studies for mood disorders through patient-level analyses of efficacy trial outcomes. In this integrative data analysis (k = 9, N = 367 patients with mood disorders), clinical outcomes were compared across four groups: ketamine (midazolam-controlled), ketamine (saline-controlled), midazolam, and saline. Ketamine doses ranged from 0.5 to 0.54 mg/kg and midazolam doses ranged from 0.02 to 0.045 mg/kg. The baseline-to-Day 1 effect size was d = 0.7 (95% CI: 0.4-0.9) for ketamine (midazolam) versus midazolam and d = 1.8 (95% CI: 1.4-2.2) for ketamine (saline) versus saline. The effect of ketamine relative to control was larger in saline-controlled studies than in midazolam-controlled studies (t(276) = 2.32, p = 0.02). This was driven by a comparatively larger effect under midazolam than saline (t(111) = 5.40, p
Intravenous Ketamine Infusions in Treatment-Resistant Bipolar Depression: An Open-Label Naturalistic Observational Study. [2022]Bipolar disorder is a chronic and recurrent condition often associated with treatment resistance and suicidality. There is an unmet need for effective treatment in this group of patients. Ketamine has been demonstrated to have antidepressant and antisuicidal properties in unipolar depression. Most of the available studies concern unipolar depression. Here, we present the efficacy and safety of IV ketamine as an add-on treatment in patients with bipolar I and bipolar II depression.
Comparative Evaluation of Ease of Dental Treatment and Clinical Efficiency of Midazolam vs Midazolam and Ketamine Combination for Sedation in Young Uncooperative Pediatric Patients: A Systematic Review. [2023]To assess and compare the effectiveness of midazolam vs midazolam and ketamine combination in the management of young uncooperative pediatric patients.