Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting

Phase 3

Recruiting

• Conditions: Severe Depression; Moderate Depression; Ketamine; Midazolam; Peripheral Nervous System Agents; Central Nervous System Agents; Neurotransmitter Agents; Physiologic Effects of Drugs; Sensory System Agents; Analgesics, Non-Narcotic
• Interventions: Drug: nebulized ketamine

• Registration Number: NCT06752759
• Lead Sponsor: Theresa Jacob, PhD, MPH

Brief Summary

This is a double blind active placebo controlled clinical trial for individuals within an inpatient setting with moderate to severe depression. The purpose of this study is to assess if nebulized ketamine can reduce depressive symptoms.

Detailed Description

The objective of this study is to evaluate the effect of ketamine formalized to be dispensed via inhalation, as an adjunct to concomitant medications and therapies on those with moderate to severe depression currently in an inpatient psychiatric unit. Investigators will examine the effects of nebulized ketamine on depressive symptoms.

This is a prospective double-blind placebo controlled study in which an active placebo, Midazolam, will be used. Participants will commit to either 4 visits or 5 visits depending on which treatment arm they are randomized into. All visits can be done remotely, however, days in which the participant will be dosed will have to be in person. During dosing days, the participant will be monitored for a minimum of two hours. Study participant's vitals will be collected at regular intervals during the observation period.

Adult psychiatry inpatients who are 18 years and older with a diagnosis of moderate to severe depression will be screened for enrollment by the study.

Study Timeline

• Study Start: 2024-10-16
• Status Verified: 2024-12
• Study First Submitted: 2024-12-23
• Study First Submitted QC: 2024-12-23
• Last Update Submitted: 2024-12-23
• Study First Posted: 2024-12-31
• Last Update Posted: 2024-12-31
• Primary Completion: 2026-09-30
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• All individuals 18 years and older within the Institution's inpatient Psychiatry Unit with a Montgomery-Asberg Depression Rating Scale score ≥ 20
• Must have a diagnosis of moderate to severe Major Depressive Disorder
• Structured Clinical Interview for DSM-5 (SCID-5) will be performed to confirm MDD diagnosis

Exclusion Criteria

• Adult patients with an allergy to ketamine
• Adult patients with an allergy to Midazolam
• Individuals with a history of mania/hypomania or diagnosis of of bipolar disorder
• Patients on lithium and/or lamotrigine therapy
• Recent or current homicidal ideation with an intent to act
• MDD with psychotic features or current or past diagnosis of a psychotic disorder
• No substance use disorder in the preceding 3 months except nicotine or caffeine or a positive urine screen for substances (except cannabis)
• Diagnosis of obsessive-compulsive disorder, antisocial personality disorder, borderline personality disorder, posttraumatic stress disorder, intellectual disability, altered mental status, pregnant or breastfeeding patients,
• Patients on > 2 medications for hypertension
• Patients with uncontrolled hypertension (BP >140 mm Hg systolic and/or >90 mm Hg diastolic on two separate readings at the time of screening)
• Body weight of > 150kg
• Patients with history of congestive cardiac failure
• Day of presentation, patients with unstable vital signs (systolic blood pressure <90 or>160 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min)
• Consumption of opioids within 24 hours of drug administration
• Acutely intoxicated patients will also be excluded

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Nebulized Midazolam	nebulized ketamine	Midazolam used as active placebo. Dosage calculated by body weight at 0.03mg/kg
Nebulized Ketamine	nebulized ketamine	Ketamine dosage calculated by body weight at 1.5mg/kg

Primary Outcome Measures

Name	Time	Method
Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS)	8-10 days	Montgomery-Asberg Depression Rating Scale has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total Montgomery Asberg Depression Rating Scale (MADRS) score from the baseline (pre-dose day 1 ), Day 2 and last day of assessments (Day 8 or Day 10)

Secondary Outcome Measures

Name	Time	Method
A change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) from the baseline (pre-dose on day 1) and 2 hours post-medication administration	8-10 days	Montgomery-Asberg Depression Rating Scale has a range from 0 to 60, where the lower score indicates the better health status. Change in mean total Montgomery-Asberg Depression Rating Scale prior to dose administration on Day 1, 2 hours after dose administration for each day.
Change in Beck Scale for Suicide Ideation	24 hours	Beck Scale for Suicide Ideation has a range from 0 to 42, where the lower score indicates the better health status. SSI score of ≥4, response which would be defined as SSI ≥50% below baseline - 2 hours post medication administration and remission defined as SSI score of ≥50% and lower than 4 - 24 hrs after medication administration of follow-up
Clinician-Administered Dissociative States Scale (CADSS)	8-10 days	Measurement of dissociative symptoms. Clinician Administered Dissociative States Scale (CADSS) comprises 23 subjective items, each on a 5 point scale, a "0" represents absence of any adverse events and "4" represents a severely bothersome side effect. A total score ranges from 0-92, a lower score indicates a better health status.
Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)	8-10 days	Overall side effects as measured by the Side Effect Rating Scale for Dissociative Anesthetics (SERSDA). SERSDA has 9 items, each graded on a five point scale, with "0" representing the absence of any adverse effects and "4" representing a severely bothersome side effect.
Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S)	8-10 days	Modified Observer's Alertness/Sedation Scale ( MOAA/S) uses a 6 point scale. A "0" indicates failure to respond to painful stimulus, "5" represents fully alert. .
Richmond Agitation-Sedation Scale (RASS)	8-10 days	Measurement of participant's consciousness with a rating ranging from +4 to -5. +4 represents "combative", +3 represents "Very agitated", +2 represents "Agitated" , +1 represents restless, 0 represents "Alert and calm", -1 represents "Drowsy", -2 represents "Light sedation", -3 represents "Moderate sedation", -4 represents "Deep sedation", and -5 represents "Unarousable".

Trial Locations

Locations (1)

Maimonides Medical Center; 🇺🇸 Brooklyn, New York, United States