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

Phase 4

Recruiting

• Conditions: Major Depressive Disorder
• Interventions: Drug: Ketamine; Drug: Esketamine

• Registration Number: NCT05450432
• Lead Sponsor: Massachusetts General Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-06-16
• Study First Submitted QC: 2022-07-05
• Study First Posted: 2022-07-08
• Study Start: 2022-10-13
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-20
• Last Update Posted: 2023-01-25
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ketamine and Esketamine Treatment	Esketamine	All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment.
Ketamine and Esketamine Treatment	Ketamine	All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Efficacy - Healthcare Utilization	24 weeks	The change in participants' healthcare utilization rates will be examined over time and compared to historical controls.
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.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States