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

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05450432

Collaborator

American Foundation for Suicide Prevention (Other)

100

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Ketamine Drug: Esketamine	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

A total of 100 participants will be enrolled in the study to receive intravenous ketamine and intranasal esketamine. Participants will be compared against matched historical control subjects identified through electronic medical records.A total of 100 participants will be enrolled in the study to receive intravenous ketamine and intranasal esketamine. Participants will be compared against matched historical control subjects identified through electronic medical records.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Jun 1, 2025

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Efficacy - Treatment Response [Weeks 4, 8, and 12-24]
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.
Efficacy - Trajectory of Suicidal Ideation [24 weeks]
The change in participants' suicidal ideation will be examined over time and compared to historical controls.
Efficacy - Trajectory of Depression [24 weeks]
The change in participants' depression will be examined over time and compared to historical controls.
Efficacy - Hospital Readmission Rates [24 weeks]
The change in participants' hospital readmission rates will be examined over time and compared to historical controls.
Efficacy - Prevalence of Suicidal Behavior [24 weeks]
The occurrence of suicidal behavior (gestures, attempts, and completed suicide) among participants will be examined over time and compared to historical controls.
Efficacy - Healthcare Utilization [24 weeks]
The change in participants' healthcare utilization rates will be examined over time and compared to historical controls.

Other Outcome Measures

Exploratory Aim - Predictors of Treatment Response [24 weeks]
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.
Exploratory Aim - Predictors of Suicidal Ideation Relapse [24 weeks]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Inpatient at a psychiatric unit at MGH
Male and female, 18-65 years of age
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
Current suicidal ideation
In good general health, as ascertained by medical history, physical examination, clinical laboratory evaluations, and/or ECG
A status of non-childbearing potential or use of an acceptable form of birth control
Owner of a mobile phone with cellular data
Ability to read, understand, and provide written and dated informed consent prior to screening
Has a treating psychiatrist, either prior to admission or at discharge from the inpatient unit

Exclusion Criteria:

Any history of previous treatment with IV ketamine
Pregnant or breastfeeding
A status of childbearing potential and is not willing to use birth control during the study
Unstable medical illness
Current diagnosis of a moderate to severe substance use disorder, within the last six months prior to screening based on DSM-5 criteria
History of bipolar disorder, or any psychotic symptoms in the current or previous depressive episodes
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)
Currently receiving ECT treatment
Currently receiving frequent or high dose benzodiazepines, opiates, barbiturates, or other CNS depressant medications
Has dementia, delirium, amnestic, or any other primary cognitive disorder
Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results
Inability to consent to or comply with the study procedures.
Other medical issues that might affect safety, study participation, or confound interpretation of study results