Nebulized Ketamine for the Treatment of Major Depressive Disorder

NCT06752759 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2023-06-05-MMC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

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; Anti-Inflammatory Agents, Non-Steroidal; Depressive Symptom; Hypnotics and Sedatives; Anti-anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics Agent

Keywords

Maimonides Medical Center; Psychiatry; Ketamine; Midazolam; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics, Dissociative; Nebulized Medications for depression; GABA Agents

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS)

  Montgomery-Asberg Depression Rating Scale (MADRS) 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)

  8-10 days

Secondary Outcomes (6)

• 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

• Change in Beck Scale for Suicide Ideation

  24 hours

• Clinician-Administered Dissociative States Scale (CADSS)

  8-10 days

• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)

  8-10 days

• Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S)

  8-10 days

Study Arms (2)

Nebulized Midazolam

ACTIVE COMPARATOR

Midazolam used as active comparator. Dosage calculated by body weight at 0.03mg/kg

Drug: nebulized midazolam

Nebulized Ketamine

EXPERIMENTAL

Ketamine dosage calculated by body weight at 1.5mg/kg

Drug: nebulized ketamine

Interventions

nebulized ketamine DRUG

The formulation of the study drug is administered via nebulizer in which the participants inhales the study drug. The dosage is calculated by body weight (1.5mg/kg).

Also known as: Ketalar

Nebulized Ketamine

nebulized midazolam DRUG

The formulation of the active comparator drug is administered via nebulizer in which the participant inhales the study drug. The dosage is calculated by body weight (0.03mg/kg).

Also known as: Midazolam

Nebulized Midazolam

Eligibility Criteria

• Age: 18 Years - 88 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Adult patients with an allergy to Ketamine
• Adult patients with an allergy to Midazolam
• Individuals with a history of mania/hypomania or diagnosis 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

Sponsors & Collaborators

• Theresa Jacob, PhD, MPH: lead

Study Sites (1)

Maimonides Medical Center

Brooklyn, New York, 11219, United States

RECRUITING

Related Publications (19)

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• Dove D, Fassassi C, Davis A, Drapkin J, Butt M, Hossain R, Kabariti S, Likourezos A, Gohel A, Favale P, Silver M, Marshall J, Motov S. Comparison of Nebulized Ketamine at Three Different Dosing Regimens for Treating Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind Clinical Trial. Ann Emerg Med. 2021 Dec;78(6):779-787. doi: 10.1016/j.annemergmed.2021.04.031. Epub 2021 Jul 3.

  PMID: 34226073 BACKGROUND

• Jonkman K, Dahan A, van de Donk T, Aarts L, Niesters M, van Velzen M. Ketamine for pain. F1000Res. 2017 Sep 20;6:F1000 Faculty Rev-1711. doi: 10.12688/f1000research.11372.1. eCollection 2017.

  PMID: 28979762 BACKGROUND

• Wilkinson ST, Farmer C, Ballard ED, Mathew SJ, Grunebaum MF, Murrough JW, Sos P, Wang G, Gueorguieva R, Zarate CA Jr. Impact of midazolam vs. saline on effect size estimates in controlled trials of ketamine as a rapid-acting antidepressant. Neuropsychopharmacology. 2019 Jun;44(7):1233-1238. doi: 10.1038/s41386-019-0317-8. Epub 2019 Jan 17.

  PMID: 30653192 BACKGROUND

• Drapkin J, Masoudi A, Butt M, Hossain R, Likourezos A, Motov S. Administration of Nebulized Ketamine for Managing Acute Pain in the Emergency Department: A Case Series. Clin Pract Cases Emerg Med. 2020 Jan 2;4(1):16-20. doi: 10.5811/cpcem.2019.10.44582. eCollection 2020 Feb.

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• Gao M, Rejaei D, Liu H. Ketamine use in current clinical practice. Acta Pharmacol Sin. 2016 Jul;37(7):865-72. doi: 10.1038/aps.2016.5. Epub 2016 Mar 28.

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• McIntyre RS, Rosenblat JD, Nemeroff CB, Sanacora G, Murrough JW, Berk M, Brietzke E, Dodd S, Gorwood P, Ho R, Iosifescu DV, Lopez Jaramillo C, Kasper S, Kratiuk K, Lee JG, Lee Y, Lui LMW, Mansur RB, Papakostas GI, Subramaniapillai M, Thase M, Vieta E, Young AH, Zarate CA Jr, Stahl S. Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation. Am J Psychiatry. 2021 May 1;178(5):383-399. doi: 10.1176/appi.ajp.2020.20081251. Epub 2021 Mar 17.

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• Yavi M, Lee H, Henter ID, Park LT, Zarate CA Jr. Ketamine treatment for depression: a review. Discov Ment Health. 2022;2(1):9. doi: 10.1007/s44192-022-00012-3. Epub 2022 Apr 15.

  PMID: 35509843 BACKGROUND

• Kohtala S. Ketamine-50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms. Pharmacol Rep. 2021 Apr;73(2):323-345. doi: 10.1007/s43440-021-00232-4. Epub 2021 Feb 20.

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• Park M, Niciu MJ, Zarate CA Jr. Novel Glutamatergic Treatments for Severe Mood Disorders. Curr Behav Neurosci Rep. 2015 Dec;2(4):198-208. doi: 10.1007/s40473-015-0050-5. Epub 2015 Oct 9.

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• Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Green CE, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013 Oct;170(10):1134-42. doi: 10.1176/appi.ajp.2013.13030392.

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• Holma KM, Melartin TK, Haukka J, Holma IA, Sokero TP, Isometsa ET. Incidence and predictors of suicide attempts in DSM-IV major depressive disorder: a five-year prospective study. Am J Psychiatry. 2010 Jul;167(7):801-8. doi: 10.1176/appi.ajp.2010.09050627. Epub 2010 May 17.

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• Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5.

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• Chung DT, Ryan CJ, Hadzi-Pavlovic D, Singh SP, Stanton C, Large MM. Suicide Rates After Discharge From Psychiatric Facilities: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2017 Jul 1;74(7):694-702. doi: 10.1001/jamapsychiatry.2017.1044.

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• Pagan Colon IE, Kroin J, Kaushal S, Khan S, Alvarez Villalba CL. Increased Readmission Rates in Younger Male Patients Due to Suicidal Risk in Newly Diagnosed Depressive Disorders After Initiation of Serotonin Reuptake Inhibitors. Cureus. 2022 Nov 28;14(11):e31987. doi: 10.7759/cureus.31987. eCollection 2022 Nov.

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• Goodwin RD, Dierker LC, Wu M, Galea S, Hoven CW, Weinberger AH. Trends in U.S. Depression Prevalence From 2015 to 2020: The Widening Treatment Gap. Am J Prev Med. 2022 Nov;63(5):726-733. doi: 10.1016/j.amepre.2022.05.014. Epub 2022 Sep 19.

  PMID: 36272761 BACKGROUND

MeSH Terms

Conditions

Depression

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

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

• Theresa Jacob, PhD, MPH

  Maimonides Medical Center

  STUDY DIRECTOR

Central Study Contacts

Jessica Poster, MD

CONTACT

718-283-8170; JPoster@maimo.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: December 31, 2024
• Study Start: October 16, 2024
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)