Treatment Resistant DepressionPhase 3NCT05625555
Predictors of Intravenous Ketamine Response in TRD
A Phase 3 study testing Ketamine and Midazolam in people with Treatment Resistant Depression and Major Depressive Disorder, run by Abraham Nunes at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression, Major Depressive Disorder, Bipolar Disorder
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 19 Jan 2024to Jul 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 21Show fewer
- 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.
- For premenopausal females who are currently sexually active with male partners:
- Negative serum beta-HCG 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
Who cannot join
- Pregnant or breastfeeding
- Allergies to ketamine or midazolam
- Body mass less than 50kg
- 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
Show all 39Show fewer
- Positive urine drug screen or history of DSM-5 substance use disorder (SUD) in the past 3 months (except nicotine, and recreational cannabis use that doesn't meet the criteria for DSM-5 substance use disorder). History of SUD with significant severity that investigators believe warrant exclusion based on clinical judgment.
- Previous or current benzodiazepine abuse history
- Psychiatric exclusion criteria:
- Previous ketamine use (therapeutic or recreational)
- 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
- Participants who have had ECT within 6 weeks prior to enrollment and/or have ECT during the trial period.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression: A Randomized, Double-Blind, Midazolam-Controlled Pilot Study
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, 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.
Read the detailed description
Study Design:
This will be a randomized, double-blinded, midazolam-controlled crossover trial. There is no perfect control agent for studies of subanaesthetic IV ketamine, but midazolam is generally thought to be superior to normal saline since it is not an antidepressant, yet is psychoactive and thus should better preserve blinding. Participants will undergo psychiatric assessment to establish diagnosis and determine suitability. After providing informed consent for participation, participants will wear a GENEActive accelerometer on the non-dominant wrist for the duration of the trial, beginning 21 days prior to the first infusion. Participants will complete a set of rating scales, anhedonia measures and computerized tasks. On Day 0 (infusion day), participants will receive either a single infusion of IV ketamine (KET) (KET; 0.5mg/kg over 40 minutes) or midazolam (MID) (MID; 30μg/kg over 40 minutes) diluted in 0.9% NaCl by an intravenous pump. Investigators will randomize infusion sequences in a 1-to-1 ratio: KET followed by MID (K→M) or vice versa (M→K). Infusions will be administered on Days 0 and 21, separated by a 20-day washout period. This duration balances the need to establish comparable baselines at each crossover phase and the ethical consideration of not allowing depressive symptoms to remain untreated for an unreasonable amount of time.
Investigators will obtain objective depression ratings with the Montgomery-Åsberg Depression Rating Scale (MADRS) on Days -1, 1, 7, 14, 20, 22, 28, 35, and 41. Participants will provide weekly self-ratings of depressive symptoms (using the Quick Inventory of Depressive Symptoms 16-item self-rated version; QIDS 16-SR). Weekly symptom monitoring will continue for 20 days following the second infusion. Anhedonia will be measured using both self-reported rating scale measures as well as behavioural task. Patients will provide self-ratings using the Snaith-Hamilton Pleasure Scale - 14 items (SHAPS), the Dimensional Anhedonia Rating Scale - 17 items (DARS), and Positive Valence System Scale - 21 items (PVSS-21). Several aspects of subjective sleep and circadian rhythms will be measured via self-report questionnaires. The Pittsburgh Sleep Quality Index (PSQI) will measure general sleep quality and sleep disturbance, and the Basic Language Morningness Scale (BALM) will be used to measure subjective chronotype (morningness-eveningness) of patients. Both will be completed by participants prior to the first infusion and 14 days after each infusion.
Participants will complete the Epworth Sleepiness Scale (ESS) to measure daytime sleepiness symptoms, as well as the Fatigue Scale Severity Scale (FSS) to measure symptoms of fatigue. Both ESS and FSS will be completed the day before and after each infusion, and every 7 days.
Study Groups:
Participants will receive either (A) 0.5mg/kg of ketamine hydrochloride or (B) 30μg/kg of MID diluted in 0.9 percent Sodium chloride (NaCl) over 40 minutes by an intravenous pump. The KET and MID doses are similar to those used in previous studies, and selected to minimize the possibility of unblinding. Participants must abstain from consuming grapefruit juice or benzodiazepines for 24 hours preceding the infusion since the former is a potent CYP3A4 inhibitor that may reduce the rate of midazolam and ketamine elimination, and the latter reduces the response to ketamine.
- Keywords
- Treatment Resistant Depression, Major Depressive Disorder, Bipolar Disorder, Clinical Prediction, Ketamine, Midazolam
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketamine Hydrochloride, Kevlar
IV Ketamine infusion 0.5mg/kg over 40 minutes
MidazolamDrug
Also called Midazolam Hydrochloride
IV Midazolam infusion 30μg/kg over 40 minutes
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants will be randomly assigned to receive Ketamine or Midazolam Receives: Drug: Ketamine |
| Midazolam | Active comparator | Participants will receive either Ketamine or Midazolam based on what they initially received Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 hours, 7 days, 14 days, 20 days
Secondary outcomes (8)
Weekly self-ratings of Generalized Anxiety Disorder 7 Scale
Generalized Anxiety Disorder 7 Scale (GAD-7) measures symptoms of anxiety. The scores for each item ranges from 0 to 3, and total scores range from 0 to 21 with higher scores indicating more severe anxiety. Researchers will investigate the degree to which clinical features predict change in participants' GAD-7 score.
Measured: 24 hours, 7 days, 14 days, 20 days
The Snaith-Hamilton Pleasure Scale
Researchers will investigate change in anhedonic symptoms after treatment based on total scores from the Snaith-Hamilton Pleasure Scale (SHAPS), which is a 14-item scale that measures anhedonia. Final scores range from 0-14 with higher scores indicates higher levels of anhedonia.
Measured: 24 hours, 20 days
Dimensional Anhedonia Rating Scale
Researchers will investigate change in anhedonic symptoms after treatment using the Dimensional Anhedonia Rating Scale (DARS). It is a 17-item scale that measures desire, motivation, effort and consummatory pleasure across four reward-related domains. Scores ranges from 0 to 68 with higher values indicating less anhedonia.
Measured: 24 hours, 20 days
The Positive Valence Systems Scale
Researchers will investigate change in anhedonic symptoms after treatment based on the total scores from the Positive Valence Systems Scale (PVSS-21). It is a 21-item scale that measures fine-grained details of hedonic capacity.
Measured: 24 hours, 20 days
Probabilistic Reward Task
Researchers will evalute change in anhedonic symptoms after treatment using the Probabilistic Reward Task is a neurocognitive computerized task that objectively measures the degree to which the patient can modulate behavior based on reward. 3 Blocks of 60 trials each are separated by thirty-second breaks. A short (11.5 mm) or Long (13 mm) mouth then appears for 100 ms, after which subjects are given a maximum of 7900 ms to indicate whether the mouth presented was short or long by pressing either the left or right shift key.
In each block, short and long mouth stimuli are shown 50 times each. The central feature of this task is that correct responses are asymmetrically rewarded. That is, for any given task administration, either the long or short mouth is designated as "rich," and the other "lean." Correct classification yields a reward 75% of the time for the "rich" stimulus, but only 30% of the time for the "lean" stimulus.
Measured: 24 hours after each infusion, 20 days after each infusion
Fatigue Severity Scale
Researchers will evaluate the effects of ketamine on change in sleep and circadian function based on Fatigue Severity Scale (FSS) is a 9-item scale that measures symptoms of fatigue. The items are scored on a 7 point scale with 1 for strongly disagree and 7 for strongly agree. The higher the score, the greater the fatigue severity.
Measured: 24 hours, 7 days, 14 days, 20 days
Epworth Sleepiness Scale
Researchers will investigate the effects of ketamine on change in sleep and circadian function based on the Epworth Sleepiness Scale (ESS). It is an 8-item scale that measures daytime sleepiness symptoms. Total scores range from 0 to 24 with higher scores representing higher levels of excessive daytime sleepiness.
Measured: 24 hours, 7 days, 14 days, 20 days
Basic Language Morningness Scale
Researchers will investigate the effects of ketamine on change in sleep and circadian function based on theBasic Language Morningness Scale (BALM), which is a 13-item scale that measures subjective chronotype (morningness-eveningness). Total scores range from 16 to 86, scores of 41 and below indicate "evening types" scores of 42-58 indicate "intermediate types" and scores of 59 and above indicate "morning types".
Measured: 24 hours, 7 days, 14 days, 20 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2022
- Study start19 Jan 2024
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Abraham Nunes
- Sponsor type
- University, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Responsible party
- Sponsor-investigator, Abraham Nunes, Nova Scotia Health Authority
- Investigators
- Abraham Nunes, MD PhD MBA FRCPC, Principal investigator, Nova Scotia Health Authority
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05625555
- Sponsor's protocol ID
- DALKETCLIN
- Status last verified
- May 2026
- First submitted
- 15 Nov 2022
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Predictors of Intravenous Ketamine Response in Treatment-Resistant Depression: A Randomized, Double-Blind, Midazolam-Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT05625555
- Acronym / sponsor ID
- DALKETCLIN
- Keywords
- Treatment Resistant Depression, Major Depressive Disorder, Bipolar Disorder, Clinical Prediction, Ketamine, Midazolam
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Abraham NunesUniversity, hospital or other
- Collaborators
- Nova Scotia Health Authority
- Study start
- 19 Jan 2024 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 23 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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, 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.
Detailed description
Study Design:
This will be a randomized, double-blinded, midazolam-controlled crossover trial. There is no perfect control agent for studies of subanaesthetic IV ketamine, but midazolam is generally thought to be superior to normal saline since it is not an antidepressant, yet is psychoactive and thus should better preserve blinding. Participants will undergo psychiatric assessment to establish diagnosis and determine suitability. After providing informed consent for participation, participants will wear a GENEActive accelerometer on the non-dominant wrist for the duration of the trial, beginning 21 days prior to the first infusion. Participants will complete a set of rating scales, anhedonia measures and computerized tasks. On Day 0 (infusion day), participants will receive either a single infusion of IV ketamine (KET) (KET; 0.5mg/kg over 40 minutes) or midazolam (MID) (MID; 30μg/kg over 40 minutes) diluted in 0.9% NaCl by an intravenous pump. Investigators will randomize infusion sequences in a 1-to-1 ratio: KET followed by MID (K→M) or vice versa (M→K). Infusions will be administered on Days 0 and 21, separated by a 20-day washout period. This duration balances the need to establish comparable baselines at each crossover phase and the ethical consideration of not allowing depressive symptoms to remain untreated for an unreasonable amount of time.
Investigators will obtain objective depression ratings with the Montgomery-Åsberg Depression Rating Scale (MADRS) on Days -1, 1, 7, 14, 20, 22, 28, 35, and 41. Participants will provide weekly self-ratings of depressive symptoms (using the Quick Inventory of Depressive Symptoms 16-item self-rated version; QIDS 16-SR). Weekly symptom monitoring will continue for 20 days following the second infusion. Anhedonia will be measured using both self-reported rating scale measures as well as behavioural task. Patients will provide self-ratings using the Snaith-Hamilton Pleasure Scale - 14 items (SHAPS), the Dimensional Anhedonia Rating Scale - 17 items (DARS), and Positive Valence System Scale - 21 items (PVSS-21). Several aspects of subjective sleep and circadian rhythms will be measured via self-report questionnaires. The Pittsburgh Sleep Quality Index (PSQI) will measure general sleep quality and sleep disturbance, and the Basic Language Morningness Scale (BALM) will be used to measure subjective chronotype (morningness-eveningness) of patients. Both will be completed by participants prior to the first infusion and 14 days after each infusion.
Participants will complete the Epworth Sleepiness Scale (ESS) to measure daytime sleepiness symptoms, as well as the Fatigue Scale Severity Scale (FSS) to measure symptoms of fatigue. Both ESS and FSS will be completed the day before and after each infusion, and every 7 days.
Study Groups:
Participants will receive either (A) 0.5mg/kg of ketamine hydrochloride or (B) 30μg/kg of MID diluted in 0.9 percent Sodium chloride (NaCl) over 40 minutes by an intravenous pump. The KET and MID doses are similar to those used in previous studies, and selected to minimize the possibility of unblinding. Participants must abstain from consuming grapefruit juice or benzodiazepines for 24 hours preceding the infusion since the former is a potent CYP3A4 inhibitor that may reduce the rate of midazolam and ketamine elimination, and the latter reduces the response to ketamine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineParticipants will be randomly assigned to receive Ketamine or Midazolam |
| Midazolam | Active comparator | Drug: MidazolamParticipants will receive either Ketamine or Midazolam based on what they initially received |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Able to fluently read in English with or without optical correction
- Ability to understand and comply with the study requirements
- 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).
Key exclusion criteria (39 listed)
- Pregnant or breastfeeding
- Allergies to ketamine or midazolam
- Body mass less than 50kg
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketamine Hydrochloride, KevlarIV Ketamine infusion 0.5mg/kg over 40 minutes | Drug | Ketamine |
| MidazolamAlso: Midazolam HydrochlorideIV Midazolam infusion 30μg/kg over 40 minutes | Drug | Midazolam |
Primary outcome
Change in Montgomery Åsberg Depression Rating Scale Score
Time frame: 24 hours, 7 days, 14 days, 20 days
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.
8 secondary outcomes
Weekly self-ratings of Generalized Anxiety Disorder 7 Scale
Time frame: 24 hours, 7 days, 14 days, 20 days
The Snaith-Hamilton Pleasure Scale
Time frame: 24 hours, 20 days
Dimensional Anhedonia Rating Scale
Time frame: 24 hours, 20 days
The Positive Valence Systems Scale
Time frame: 24 hours, 20 days
Probabilistic Reward Task
Time frame: 24 hours after each infusion, 20 days after each infusion
Fatigue Severity Scale
Time frame: 24 hours, 7 days, 14 days, 20 days
Epworth Sleepiness Scale
Time frame: 24 hours, 7 days, 14 days, 20 days
Basic Language Morningness Scale
Time frame: 24 hours, 7 days, 14 days, 20 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abraham Nunes, MD PhD MBA FRCPC principal investigator
Nova Scotia Health Authority
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ketamine and Midazolam in people with Treatment Resistant Depression and Major Depressive Disorder, run by Abraham Nunes at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Montgomery Åsberg Depression Rating Scale Score (time frame: 24 hours, 7 days, 14 days, 20 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.