Long-Term Maintenance With Ketamine and Esketamine for Reduction of Suicide in High-Risk Patients With Depression

The study will consist of a 24-week-long trial examining outcomes in patients with Major Depressive Disorder and suicidal ideation who will receive intravenous (IV) ketamine and intranasal (IN) esketamine, compared to a large sample of matched historical controls. Patients will be recruited from an inpatient psychiatric unit. Eligible patients who provided informed consent will be enrolled in the study that will include a eight IV ketamine treatments, 13 esketamine treatment visits, seven long assessment visits, five short assessment visits, and daily surveys. The study will examine the feasibility, tolerability, and efficacy of repeated IV ketamine followed by esketamine, as well as predictors of treatment response.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ketamine; Drug: Esketamine

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cristina Cusin, MD; Phone Number: 617-724-5510; Email: mghketamineclinic@mgh.harvard.edu
• Study Contact Backup: Name: Julianne Origlio; Phone Number: 617-643-2497; Email: joriglio@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Cristina Cusin, MD
      • Contact: Julianne Origlio; Phone Number: 617-643-2497

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:

1. Inpatient at a psychiatric unit at MGH
2. Male and female, 18-70 years of age
3. Diagnosis of Major Depressive Disorder, single or recurrent, based on DSM-5 criteria, and currently experiencing a major depressive episode (MDE) at least eight weeks in duration, prior to screening
4. Current suicidal ideation
5. In good general health, as ascertained by medical history, physical examination, clinical laboratory evaluations, and/or ECG
6. A status of non-childbearing potential or use of an acceptable form of birth control
7. Access to a mobile phone or computer with internet connection
8. Ability to read, understand, and provide written and dated informed consent prior to screening
9. Has a treating psychiatrist, either prior to admission or at discharge from the inpatient unit

Exclusion Criteria:

1. Any history of previous treatment with IV ketamine
2. Pregnant or breastfeeding
3. A status of childbearing potential and is not willing to use birth control during the study
4. Unstable medical illness
5. Current diagnosis of a moderate to severe substance use disorder, within the last six months prior to screening based on DSM-5 criteria
6. History of bipolar disorder, or any psychotic symptoms in the current or previous depressive episodes
7. An Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening (i.e., eating disorder, OCD, PTSD)
8. Currently receiving ECT treatment
9. Currently receiving frequent or high dose benzodiazepines, opiates, barbiturates, or other CNS depressant medications
10. Has dementia, delirium, amnestic, or any other primary cognitive disorder
11. Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results
12. Inability to consent to or comply with the study procedures.
13. Other medical issues that might affect safety, study participation, or confound interpretation of study results
14. Inability to comply with study safety procedures, including having reliable escorts to and from visits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Ketamine and Esketamine Treatment; All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment.

Drug: Ketamine; Study participants will start treatment including two ketamine infusion visits per week during the acute phase, for up to eight ketamine infusion visits. Participants will then be transitioned to maintenance with intranasal esketamine.; Drug: Esketamine; After one month from the eighth ketamine infusion visit, participants will initiate weekly esketamine for 12 weeks, for a total of 13 esketamine treatments. The esketamine visits will happen as per standard of care at the clinic and as instructed by the SPRAVATO Risk Evaluation and Mitigation Strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility - Retention	For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' retention across study visits.	24 weeks
Feasibility - Drop-out Rates	For examining the feasibility of treatment with ketamine and esketamine, descriptive analyses will be conducted to assess participants' drop-out rates across participation in the study.	24 weeks
Tolerability - Cognitive Function and Side Effects	In regard to tolerability, the investigators will closely monitor cognitive functions and side effects during the administration of ketamine and esketamine.	Weeks 0, 1, 2, 3, 4, 8, and 12-24
Tolerability - Dosage of Treatment	In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for dosage of ketamine and esketamine treatments.	Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24
Tolerability - Frequency of Treatment	In regard to tolerability, the investigators will record the Necessary Clinical Adjustments (NCAs) for the frequency of ketamine and esketamine administration.	Change between weeks 0, 4, 6, 8, 10, 12, 14, 16, 20, 22, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - Treatment Response	Descriptive analyses will be performed for percentage of responders (defined as 35% improvement on the QIDS-16) at the end of the IV ketamine acute phase, after the eighth ketamine infusion, and across the esketamine maintenance phase.	Weeks 4, 8, and 12-24
Efficacy - Trajectory of Suicidal Ideation	The change in participants' suicidal ideation will be examined over time and compared to historical controls.	24 weeks
Efficacy - Trajectory of Depression	The change in participants' depression will be examined over time and compared to historical controls.	24 weeks
Efficacy - Hospital Readmission Rates	The change in participants' hospital readmission rates will be examined over time and compared to historical controls.	24 weeks
Efficacy - Prevalence of Suicidal Behavior	The occurrence of suicidal behavior (gestures, attempts, and completed suicide) among participants will be examined over time and compared to historical controls.	24 weeks
Efficacy - Healthcare Utilization	The change in participants' healthcare utilization rates will be examined over time and compared to historical controls.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Aim - Predictors of Treatment Response	Exploratory aims will be examined, including predictors of treatment response (defined as 35% improvement in QIDS score) at the end of the acute and maintenance phases.	24 weeks
Exploratory Aim - Predictors of Suicidal Ideation Relapse	Exploratory aims will be examined, including predictors of suicidal ideation relapse (defined as SSI5>1) during time intervals between intravenous ketamine visits and during the esketamine maintenance phase.	24 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: American Foundation for Suicide Prevention

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2022
• Primary Completion (Anticipated): June 1, 2025
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: June 16, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 8, 2022

Study Record Updates

• Last Update Posted (Actual): January 25, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: depression; suicidal ideation
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Self-Injurious Behavior; Depression; Depressive Disorder; Suicide; Depressive Disorder, Major; 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; Psychotropic Drugs; Antidepressive Agents; Ketamine; Esketamine
• Other Study ID Numbers: 2022P000972

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: The investigators do not plan to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No