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

NCT05450432 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2022P000972
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

depression; suicidal ideation

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• Efficacy - Treatment Response

  Weeks 4, 8, and 12-24

• Efficacy - Trajectory of Suicidal Ideation

  24 weeks

• Efficacy - Trajectory of Depression

  24 weeks

• Efficacy - Hospital Readmission Rates

  24 weeks

• Efficacy - Prevalence of Suicidal Behavior

  24 weeks

Other Outcomes (2)

• Exploratory Aim - Predictors of Treatment Response

  24 weeks

• Exploratory Aim - Predictors of Suicidal Ideation Relapse

  24 weeks

Study Arms (1)

Ketamine and Esketamine Treatment

OTHER

All study subjects will receive intravenous (IV) ketamine and intranasal (IN) esketamine treatment.

Drug: Ketamine; Drug: Esketamine

Interventions

Ketamine DRUG

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.

Ketamine and Esketamine Treatment

Esketamine DRUG

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.

Ketamine and Esketamine Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Inpatient at a psychiatric unit (or MGH medical unit, awaiting transfer to psychiatry).
• Male and female, 18-70 years of age, inclusive, at screening.
• Diagnosis of MDD, single or recurrent, and currently experiencing a major depressive episode (MDE) at least eight weeks in duration, prior to screening, according to the criteria defined in the Diagnosis and Statistical manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis of MDD will be made by a site psychiatrist and supported by the Mini-International Neuropsychiatric Interview (MINI).
• Suicidal ideation determined by a minimum score of 1 on item 12 of the QIDS-C assessment and based on admission to the inpatient unit for suicidal thoughts or behaviors.
• In good general health, as ascertained by medical history. If needed to verify health status, the investigator may order/conduct physical examination (PE) (including measurement of supine and standing vital signs), clinical laboratory evaluations, or ECG.
• A status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:
• \. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or 2. Childbearing potential, and meets the following criteria:
• Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.
• Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test prior to receiving study treatment.
• Willing and able to continuously use a method of birth control during the course of the study (implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence). The form of birth control will be documented at screening.
• \. 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.
• \. Must have a provider to manage psychiatric medication, such as a psychiatrist, nurse practitioner, primary care physician, etc., either prior to admission or at discharge from the inpatient unit.

You may not qualify if:

• Any history of previous treatment with IV ketamine.
• Pregnant or breastfeeding.
• Subject of childbearing potential who is not willing to use birth control during the study.
• Unstable medical illness, i.e., severe liver or kidney disease, uncontrolled hypertension, uncontrolled hyperthyroidism
• Current diagnosis of a moderate to severe substance use disorder (excluding mild or moderate alcohol or cannabis use disorder which will be permitted), 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, based on an increased risk of sedation in combination with ketamine.
• 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 according to a licensed physician on the study staff.
• Inability to consent to or comply with the study procedures.
• Other medical issues:
• Hypertension, (SBP ≥160 mmHg or DBP ≥100 mHg) at Screening - untreated
• Recent myocardial infarction (within one year)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• American Foundation for Suicide Prevention: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression; Suicidal Ideation

Interventions

Ketamine; Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior; Suicide; Self-Injurious Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Cristina Cusin, MD

CONTACT

617-724-5510; mghketamindstudy@partners.org

Catherine Schuessler, BS

CONTACT

617-643-7690; mghketamindstudy@partners.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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.

Study Record Dates

• First Submitted: June 16, 2022
• First Posted: July 8, 2022
• Study Start: October 13, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)