Predictors of Intravenous Ketamine Response in TRD

NCT05625555 | Recruiting Phase 3 DMC

• 1 other identifier: DALKETCLIN
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

For patients with treatment-resistant depression (TRD), a single low dose of intravenous (IV) ketamine can help relieve symptoms as quickly as 24 hours later. The main problem with IV ketamine for TRD is that the effect is short-lived, lasting only days to 1 or 2 weeks. Furthermore, IV ketamine is a resource-intensive treatment, and the safety of long-term, repeated use for depression is unknown. To provide this treatment in a safe and cost-effective way, Investigators must allocate it efficiently to those patients who have the greatest need and probability of benefit. Therefore, this project aims to find clinical features (signs, symptoms, and parts of a patient's history) that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD. This will help guide patient selection and triaging. Investigators will recruit 40 participants with TRD over one year, and randomize them to one of two conditions (ketamine followed by an active placebo 3-weeks later, or vice versa). With clinical data collected through detailed interviews, questionnaires, actigraphy, speech sampling, electroencephalography (EEG), and computerized tasks, this study design will let us evaluate how well such factors predict (A) rapid response at 24-hours, and (B) sustained response at 7 and 14 days.

Conditions

Treatment Resistant Depression; Major Depressive Disorder; Bipolar Disorder

Keywords

Treatment Resistant Depression; Major Depressive Disorder; Bipolar Disorder; Clinical Prediction; Ketamine; Midazolam

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery Åsberg Depression Rating Scale Score

  Montgomery Åsberg Depression Rating Scale (MADRS) measures depressive symptoms. The scores for each item ranges from 0 to 6 and total scores range from 0 to 60, with higher scores indicating more severe depression. Researchers will investigate the degree to which each clinical feature predicts Days 1, 7, 14, and 20 post-infusion MADRS using a biomarker prediction model.

  24 hours, 7 days, 14 days, 20 days

Secondary Outcomes (8)

• Weekly self-ratings of Generalized Anxiety Disorder 7 Scale

  24 hours, 7 days, 14 days, 20 days

• The Snaith-Hamilton Pleasure Scale

  24 hours, 20 days

• Dimensional Anhedonia Rating Scale

  24 hours, 20 days

• The Positive Valence Systems Scale

  24 hours, 20 days

• Probabilistic Reward Task

  24 hours after each infusion, 20 days after each infusion

Other Outcomes (3)

• Migraine Severity Questionnaire

  7 days

• Measures of psychomotor behaviour to predict depressive severity

  14 days before the first infusion, 7 days before the first infusion, 1 day before the first infusion, day of the infusions, 24 hours, 7 days, 20 days after each infusion

• Effect of treatment on mnemonic discrimination performance in depression

  24 hours before the infusions, 24 hours after the infusions, 20 days after the infusions.

Study Arms (2)

Ketamine

EXPERIMENTAL

Participants will be randomly assigned to receive Ketamine or Midazolam

Drug: Ketamine

Midazolam

ACTIVE COMPARATOR

Participants will receive either Ketamine or Midazolam based on what they initially received

Drug: Midazolam

Interventions

Ketamine DRUG

IV Ketamine infusion 0.5mg/kg over 40 minutes

Also known as: Ketamine Hydrochloride, Kevlar

Ketamine

Midazolam DRUG

IV Midazolam infusion 30μg/kg over 40 minutes

Also known as: Midazolam Hydrochloride

Midazolam

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to fluently read in English with or without optical correction
• Ability to understand and comply with the study requirements
• This is determined by the investigators
• Provision of written informed consent
• Documented diagnosis of MDD or bipolar disorder meeting DSM-5 criteria (as confirmed by the Diagnostic Assessment Research Tool), currently in a single or recurrent episode without psychotic features
• Failure of at least two antidepressant medications from different pharmacological classes, as well as at least one augmentation agent, each of which must have been given at adequate doses for at least 6 weeks (recorded using the Antidepressant Treatment History Form - Short Form).
• Augmentation strategies include those listed in the 2016 Canadian Network for Mood and Anxiety Treatments (CANMAT) depression guidelines, including a 12-week course of cognitive behavioural therapy or interpersonal therapy.
• MADRS score of ≥25 at initial assessment and Day -1, and no more than 20% improvement between those visits.
• For premenopausal females who are currently sexually active with male partners:
• Negative urine pregnancy test at enrolment
• AND commitment to using an appropriate birth control method of their choice throughout the duration of the study, including
• Intrauterine device
• Oral contraceptive
• Long-term injectable contraceptive
• Double-barrier method

You may not qualify if:

• Pregnant or breastfeeding
• Allergies to ketamine or midazolam
• Concomitant use of medications with the potential for clinically significant interactions with either ketamine or midazolam (e.g., monoamine oxidase inhibitors, methylene blue)
• Concomitant use of naltrexone or narcotics
• Positive urine drug screen or history of DSM-5 substance use disorder (except caffeine or nicotine)
• Previous or current benzodiazepine abuse history
• Previous ketamine use (therapeutic or recreational)
• History of electroconvulsive therapy
• Comorbid DSM-5 personality disorder with a major impact on mental status
• Secondary depressive disorders
• E.g. secondary to stroke, cancer, or other somatic pathology
• Subjects who will be starting psychotherapy during the trial period, or have only recently started psychotherapy within 2 months of the trial
• Evidence on history or chart review of any of the following:
• Epilepsy
• Any current or historical occurrence of renal disease

Sponsors & Collaborators

• Abraham Nunes: lead
• Nova Scotia Health Authority: collaborator

Study Sites (1)

Mood Disorders Program

Halifax, Nova Scotia, B3H2E2, Canada

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Bipolar Disorder

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Abraham Nunes, MD PhD MBA FRCPC

  Nova Scotia Health Authority

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa Pardo, BA (Hons)

CONTACT

902-473-2585; Vanessa.Pardo@nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Psychiatrist/Assistant Professor

Model Details: Participants will receive either a single infusion of IV Ketamine (KET; 0.5mg/kg over 40 minutes) or Midazolam (MID; 30μg/kg over 40 minutes). Investigators will randomize infusion sequences in a 1-to-1 ratio: KET followed by MID or vice versa. Infusions will be administered on Day 0 and Day 21, separated by a 20-day washout period.

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: November 23, 2022
• Study Start: January 19, 2024
• Primary Completion: January 1, 2025
• Study Completion: February 1, 2025
• Last Updated: February 9, 2024

Record last verified: 2024-02

Locations

CA (1)