Intramuscular Ketamine for Suicidal Ideation

Intramuscular Ketamine Administration for the Treatment of Acute Suicidal Ideation With Concurrent EEG Monitoring

The objective of the present research protocol, a cross-over, subject-blinded, clinical trial, is to correlate changes in brain activity with reduction in suicidal ideation in response to a single intramuscular dose of ketamine. While ketamine is increasingly used as a rapid, antidepressant agent, there is accumulating evidence of additional anti-suicidal properties that may be distinct from its effects on depression. This pilot study will be used to determine (1) whether specific electroencephalogram (EEG) findings are correlated with response of SI to intramuscular (IM) ketamine, and (2) the effectiveness of IM ketamine in the treatment of acute SI.

Study Overview

• Status: Withdrawn
• Conditions: Suicidal Ideation
• Intervention / Treatment: Drug: Ketamine (Ketalar); Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Current clinically significant suicidal ideation, defined as a score of > or = 4 on the MADRS item 10 and a positive answer on items 3,4 or 5 of the C-SSRS.
• Inpatient status at the time of study initiation.
• 18 to 70 years of age
• Capacity to consent

Exclusion criteria:

• Diagnosis of a primary psychotic disorder (e.g., schizoaffective disorder)
• Diagnosis of pervasive developmental disorder
• Diagnosis of a major neurocognitive disorder
• A positive urine pregnancy test
• Currently breastfeeding
• Drug or alcohol abuse or dependence within the preceding 3 months; a rather narrow time period was chosen, however, in order to allow participation by individuals with a history of substance abuse or dependence problems that could be secondary to their SI, and to more closely approximate patients seen in real-world settings. Given the increasingly widespread use of marijuana, and in an effort to recruit a naturalistic study population, concurrent marijuana use is not an exclusion criterion, as long as they are not actively intoxicated.
• Current positive UTOX for amphetamine, benzodiazepines, cocaine, opiates (if not prescribed)
• Medical issues or laboratory abnormalities requiring acute intervention
• Patients for whom an increase in blood pressure or intracranial pressure would pose a serious risk (e.g., aneurysmal vascular disease, arteriovenous malformation, history of intracerebral hemorrhage, unstable angina)
• Any lifetime history of ketamine or phencyclidine abuse
• A known hypersensitivity to or history of a serious adverse effect from to ketamine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine (1) then Placebo (2); Participants will receive an intramuscular injection of racemic ketamine, followed the next day by an intramuscular injection of saline (placebo)	Drug: Ketamine (Ketalar); 0.5 mg/kg of body weight; Drug: Placebo; IM injection of matching placebo
Placebo Comparator: Placebo (1) then Ketamine (2); Participants will receive an intramuscular injection of saline (placebo), followed the next day by an intramuscular injection of racemic ketamine	Drug: Ketamine (Ketalar); 0.5 mg/kg of body weight; Drug: Placebo; IM injection of matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Auditory Mismatch Negativity (EEG)	Change in Mismatch Negativity (MMN) amplitude or latency from baseline up to one hour after injection.	Baseline and One hour post injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Montgomery-Asberg Depression Rating Scale (MADRS) #10 (SI)	Change in MADRS #10 from baseline to 24 hours post-injection. Score range from 0-5, with higher score indicating higher severity of symptoms.	Baseline and 24 hours post injection

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Matthew Klein, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Actual): March 24, 2022
• Study Completion (Actual): March 24, 2022

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: October 22, 2021
• First Posted (Actual): November 3, 2021

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Ketamine; Suicide; EEG
• Additional Relevant MeSH Terms: Behavioral Symptoms; Self-Injurious Behavior; Suicide; Suicidal Ideation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: STUDY-20-01496; 21-1174 (Other Identifier: American Foundation for Suicide Prevention)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal. Any purpose. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data will be made available the completion of the study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No