Nebulized Ketamine for the Treatment of Major Depressive Disorder

Официальное название

Nebulized Ketamine for the Treatment of Major Depressive Disorder in an Inpatient Setting: A Midazolam-controlled Randomized Controlled Trial

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат nebulized ketamine
  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).
• Препарат nebulized midazolam
  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).

Первичные конечные точки

• Change in depressive symptoms on the Montgomery-Åsberg Depression Rating Scale (MADRS) [Срок оценки: 8-10 days]

Вторичные конечные точки (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 [Срок оценки: 8-10 days]
• Change in Beck Scale for Suicide Ideation [Срок оценки: 24 hours]
• Clinician-Administered Dissociative States Scale (CADSS) [Срок оценки: 8-10 days]
• Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) [Срок оценки: 8-10 days]
• Maximal sedative effects using Modified Observer's Assessment of Alertness and Sedation ( MOAA/S) [Срок оценки: 8-10 days]
• Richmond Agitation-Sedation Scale (RASS) [Срок оценки: 8-10 days]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Maimonides Medical Center — Brooklyn

Публикации

• Andrade C. Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action. J Clin Psychiatry. 2017 Apr;78(4):e415-e419. doi: 10.4088/JCP.17f11567. PMID 28448702
• 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. E PMID 34226073
• 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
• 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
• 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. PMID 32064416
• 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. PMID 27018176
• 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 Op PMID 33726522
• 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

Идентификаторы

NCT: NCT06752759 · 2023-06-05-MMC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗