RecruitingPhase 3ACTRN12624000789561

The Kite Trial: Examining the Effectiveness of Ketamine for Adults with Bipolar Depression

Ketamine for Adults with Bipolar Depression (the Kite Trial): A Randomised, Double-blind, Midazolam-controlled, Multicentre Clinical Trial

Sponsor

The University of Melbourne

Enrollment

98 participants

Start Date

Oct 29, 2024

Study Type

Interventional

Conditions

Bipolar Disorder

Summary

The Kite trial is a clinical trial of adults (18+) with bipolar disorder I or II who are currently experiencing a major depressive episode. The primary research aims to determine if a 3-week course of low-dose ketamine administered twice- weekly is an effective treatment for adults with moderate-to-severe bipolar depression, in addition to treatment-as-usual. Participants must be taking a mood-stabilising medication for the duration of the trial. 98 male and female participants will be recruited. In the Randomised Controlled Trial (RCT) phase, participants will be randomly assigned to receive either low-dose ketamine or an active control treatment (midazolam) via subcutaneous injection, twice a week for three weeks. Change in depression symptom scores will be assessed at the end of week 3. After completing this phase, some participants will advance to a second phase where they will receive a further 3 weeks of twice- weekly open label ketamine treatment to further evaluate its safety profile and effectiveness. All participants will complete follow-up assessments at Day 39 and Day 81. The research aims to offer valuable data on ketamine's potential benefits in treating depression in people with bipolar disorder.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria5

Consent and Capacity: Eligible participants must be able to provide written informed consent, demonstrating adequate intellectual capacity and fluency in English.
Age Requirement: Participants must be aged 18 years or older at the time of informed consent. Diagnosis: Participants must meet the DSM-5 criteria for either bipolar I or bipolar II disorder, currently experiencing a Major Depressive Episode, confirmed using the Structured Clinical Interview for DSM-5 (SCID-5).
Depression Severity: Participants must present with moderate-to-severe depression (as indicated by MADRS score greater than or equal to 20).
Stable Pharmacotherapy: Participants must be receiving stable pharmacotherapy treatment with one or more mood stabilising medications, which can include lithium, anti-convulsants, and atypical antipsychotics, for at least 28 days prior to the first treatment visit (Day 1) and must remain stable throughout the trial (unless changes are clinically indicated);
Reproductive Health Requirements: People of Childbearing Potential (POCBP) must have a negative pregnancy test, not be breastfeeding, and use effective contraception throughout the study. Additionally, abstention from egg or sperm donation during and following the study is required, with specific time frames set for each.

Exclusion Criteria5

Excluded Diagnoses: Participants should not meet DSM-5 criteria for current major depressive episodes with mixed features, rapid cycling bipolar disorder, schizoaffective disorder, or schizophrenia.
Compliance Issues: Participants with severe disturbances that prevent compliance with the study requirements or informed consent are excluded.
Medical Contradictions: Those with unstable medical conditions or contraindications to ketamine or midazolam use, according to product information forms, are not eligible.
Substance Use: Any history of ketamine use disorder or substance use disorder of at least moderate severity within the past 6 months excludes participation.
Concurrent Trial Participation: Participation in another clinical trial from the first day of this trial until the first follow-up visit (Day 39) disqualifies prospective participants.

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Interventions

Randomised Controlled Trial (RCT) Phase: The intervention in the Kite trial during the 3-week RCT treatment phase is low-dose subcutaneous ketamine, administered twice a week. The starting dose for k

Randomised Controlled Trial (RCT) Phase: The intervention in the Kite trial during the 3-week RCT treatment phase is low-dose subcutaneous ketamine, administered twice a week. The starting dose for ketamine will be 0.6 mg/kg, or 0.025 mg/kg of midazolam (Level 1). Dose levels may be titrated at subsequent treatment visits in a step-wise manner, with the maximum dose level being Level 4 and the lowest level being Level 0. Between dose levels 1 and 3, there are 0.25 mg/kg increments in ketamine and 0.0075 mg/kg in midazolam. The final dose level increment from level 3 to level 4 is 0.2 mg/kg of ketamine and 0.010 mg/kg of midazolam. Treatments will be administered twice per week, with sessions separated by a minimum of two days. The total duration of the RCT phase is 3 weeks, with a maximum of 6 treatments received in this period. The study drug will be administered via subcutaneous injection which will be performed by a research team member, specifically a trained nurse or study doctor, with confirmed proficiency in subcutaneous administration and controlled drug management, adhering to Australian clinical trial and local state regulations and Good Clinical Practice (GCP). The Montgomery-Asberg Depression Rating Scale (MADRS) will be administered immediately before RCT treatments 2, 3, 4, 5, and 6, or within 24 hours prior to the planned administration of these treatments. Participants with inadequate treatment response – defined as less than a 50% reduction in baseline scores on the MADRS) – will receive an increased dose at that treatment session if the previous dose was well-tolerated. Tolerability of the acute response to treatment post-administration will also be assessed using the standardised Ketamine Side-Effects Tool (KSET), the Brief Psychiatric Rating Scale (BPRS), and the Clinician Administered Dissociative Symptoms Scale-6 Item (CADSS-6) questionnaire. Those who are unable to tolerate dose levels 1 - 4 may be down-titrated to lower levels. Participants who are unable to tolerate the starting dose will have their dosage reduced for subsequent treatments to the minimum dose of 0.5 mg/kg. All treatments are administered in person by a member of the study team. Adherence to treatments will be monitored by the study team through regular checks at the study site. Each treatment will be entered into the study-specific database to ensure adherence. Open Label Extension (OLE) Phase: Participants who continue into the OLE phase may receive an additional three weeks of twice-weekly open-label ketamine. Entry into the OLE phase will occur within three-to-four days after completion of the last RCT phase treatment. Dose titration will follow the same methodologies outlined during the RCT phase. However, participants who were randomised to receive ketamine during the RCT phase will start their OLE treatment at the last dose level of the RCT phase and may be titrated according to response and tolerability at subsequent treatment visits.