Predicting who will respond to intravenous ketamine for treatment-resistant depression
Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression: A Randomized, Double-Blind, Midazolam-Controlled Pilot Study
This study is trying to find out which patients with treatment-resistant depression are most likely to benefit from a single low dose of intravenous ketamine.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 18 Years to 65 Years |
| Sex | All |
| Sponsor | Nova Scotia Health Authority Academic / other |
| Locations | 1 site (Halifax, Nova Scotia) |
| Trial ID | NCT05625555 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to identify clinical features that predict which patients with treatment-resistant depression (TRD) are most likely to benefit from a single low dose of intravenous ketamine. The study will involve 40 participants who will be randomized to receive either ketamine or midazolam in a double-blinded, crossover design. Participants will undergo psychiatric assessments and wear accelerometers to monitor activity levels, while their depression symptoms will be evaluated using standardized rating scales. The goal is to improve the efficiency and safety of ketamine treatment by selecting the right patients for this intervention.
Who should consider this trial
Good fit: Ideal candidates are adults with a documented diagnosis of major depressive disorder or bipolar disorder who have not responded to at least two different classes of antidepressant medications.
Not a fit: Patients who have not experienced treatment-resistant depression or those with psychotic features in their depressive episodes may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to more effective and targeted use of intravenous ketamine for patients suffering from treatment-resistant depression.
How similar studies have performed: Other studies have explored the use of ketamine for depression, but this specific predictive approach is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 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
* Implant
* Dermal contraception
* Tubal ligation
* Abstinence from grapefruit juice consumption on the day of infusion
* Abstinence from benzodiazepine use within 24 hours of infusion
* Adherence to maintaining current antidepressant management
Exclusion Criteria:
* 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)
* Substance related exclusion criteria:
* 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
* Psychiatric exclusion criteria:
* 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
* Medical comorbidity related exclusion criteria:
* Evidence on history or chart review of any of the following:
* Epilepsy
* Any current or historical occurrence of renal disease
* Clinically significant abnormalities of liver function tests (total bilirubin, albumin, prothrombin time and international normalized ratio \[PT/INR\], gamma-glutamyl transferase \[GGT\], alkaline phosphatase \[ALP\]). Clinical significance of any abnormal liver function tests will be evaluated by the study anesthesiologists. Patients with clinically significant abnormalities suggesting hepatic disease will be excluded.
* Liver enzymes (AST, ALT) three times the upper normal limit at screening
* Exception: of history of acute kidney injury or transient reductions in glomerular filtration rate that have fully resolved for at least three months
* Any current or historical occurrence of hepatic disease
* Abnormal liver function tests
* Liver enzymes three times the upper normal limit at screening
* Exception: History of transient elevations of liver enzymes or reduction in liver function that have re-normalized for the past three months (as per criteria above concerning function/enzymes)
* Myocardial infarct within a year prior to initial randomization
* Chronic obstructive pulmonary disease
* Untreated obstructive sleep apnea
* Cerebrovascular disease (including history of cerebrovascular accident)
* Intracerebral structural lesions
* Viral hepatitis B or C
* Acquired immunodeficiency syndrome
* Interstitial cystitis
* Glaucoma
* Uncontrolled hypertension
* Decompensated heart failure
* Current uncorrected thyroid pathology or recent correction within 30 days (correction of thyroid function for longer than 1 month is admissible).
* Any unstable somatic pathology or clinically significant investigational abnormality (biochemical, ECG) that investigators believe would be negatively impacted by study procedures or that would negatively impact study procedures
Where this trial is running
Halifax, Nova Scotia
- Mood Disorders Program — Halifax, Nova Scotia, Canada (Recruiting)
Study contacts
- Principal investigator: Abraham Nunes, MD PhD MBA FRCPC — Nova Scotia Health Authority
- Study coordinator: Vanessa Pardo, BA (Hons)
- Email: Vanessa.Pardo@nshealth.ca
- Phone: 902-473-2585
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.