Ketamine Treatment of Youth Suicide Attempters

• ClinicalTrials.gov Identifier: NCT04763343
• Recruitment Status: Not yet recruiting
• First Posted: February 21, 2021
• Last Update Posted: February 22, 2022
• Sponsor: Tatiana Falcone, MD
• Collaborators: National Institutes of Health (NIH); National Institute of Mental Health (NIMH); Massachusetts General Hospital
• Information provided by (Responsible Party): Tatiana Falcone, MD, The Cleveland Clinic

Study Description

Brief Summary:

Ketamine, an NMDA antagonist, has been shown to have rapid anti- suicidal effects. However, its safety and efficacy and special populations has not been investigated and documented. Several reports in adults suggest rapid decrease of suicidal ideation. In the last decade there is an alarming increase of the number of suicide attempts in patients ages 15-24. Suicide is the second leading cause of death in this population. Patients with previous history of suicide attempt, are even in a higher risk category. The present study focus in this high risk group of suicide attempters. This will be a randomized controlled trial enrolling 140 youth between the ages 15- 24 after a suicide attempt; patients will be randomized to receive Ketamine 0.5 mg/kg over 40 minutes or normal saline. Patients will receive all Ketamine or placebo infusions while admitted in the Inpatient Psychiatry Service. Patients will receive up to 6 ketamine or placebo infusions until, for 3 consecutive sessions, they have a clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal, or they have been discharged from the inpatient unit. Patients will participate in weekly sessions of Collaborative Assessment for the management of Suicidality (CAMS), from the first week of the study while admitted to the hospital and will continue it on a weekly basis post-discharge until, as an outpatient, they have a clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal, for at least 3 consecutive sessions of CAMS.

Condition or disease	Intervention/treatment	Phase
Suicide, Attempted	Drug: Ketamine Hydrochloride; Drug: Saline; Behavioral: CAMS Therapy	Phase 3

Detailed Description:

Suicide is the second leading cause of death in 15-24 year-olds and accounts for 13% of all adolescent deaths annually. According to the CDC, the suicide rate for 10-24 year-olds increased in the last decade, with the suicide rate for 10-14 year-olds, 15-18 year-olds, and 20-24 year-olds increasing 177%, 76%, and 36%, respectfully. There is a critical need to develop fast and effective treatment in this highest-risk age group. Therefore, there is an urgent need to develop rapid, safe and feasible treatment to decrease suicidality in youth admitted to inpatient psychiatry after a serious suicidal attempt.

This proposal seeks to address this critical clinical gap by conducting an inpatient trial of treatment with ketamine vs placebo (saline) for rapid reversal of patients' suicidal state. Furthermore, this study will also test whether ketamine facilitates the effectiveness of collaborative psychotherapy for an enduring anti-suicidal response. One hundred and forty subjects who are medically stable admitted to inpatient psychiatry after a serious suicide attempt (defined as any act of self-harm with an intent to die) with continued suicidal ideation will be included in the study. After initial assessment, in conjunction with an anesthesiologist for any contraindication of using ketamine, patients will be randomized to receive either ketamine infusion 0.5 mg/kg over 40 minutes or saline. Ketamine or saline infusions on alternate days over two weeks will be given until subject reports no suicidal ideation for three consecutive sessions, or a maximum administration of six infusions is reached, or until they are discharged from the hospital. Concurrently, weekly sessions of CAMS will be started and continued as an outpatient after the patient is discharged until the subject also reports no suicidal ideation as an outpatient for three consecutive sessions. Monthly assessments for suicidal ideation, attempts and readmissions will be conducted as an outpatient for 3 months.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Double Blind, Placebo Controlled
• Primary Purpose: Treatment
• Official Title: Ketamine Treatment of Youth Suicide Attempters for Fast Reduction of Severe Suicide Risk and Facilitation of Long-term Collaborative Clinical Engagement: A Double Blind Randomized Placebo Controlled Trial
• Estimated Study Start Date: April 2022
• Estimated Primary Completion Date: June 2024
• Estimated Study Completion Date: August 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ketamine Treatment + CAMS Therapy	Drug: Ketamine Hydrochloride; Ketamine hydrochloride will be given as an intravenous infusion using a standard regimen given in most studies conducted: 0.5 mg/kg over 40 minutes. Ketamine infusions will be given every other day until either the subject reports clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal for three consecutive pre-infusion ratings, or a maximum of six infusions have been given over the course of 2 weeks, or they have been discharged from the inpatient unit.; Behavioral: CAMS Therapy; CAMS weekly sessions will also be started immediately as an inpatient at the start of the study while receiving ketamine or saline. CAMS will be continued weekly after the patient is discharged and followed up as an outpatient. Weekly CAMS sessions will be terminated after the subject, as an outpatient, has a clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal, for at least 3 consecutive sessions of CAMS.
Placebo Comparator: Saline Placebo Treatment + CAMS Therapy	Drug: Saline; Subjects randomized to placebo will be administered a saline (0.9% sodium chloride) drip for 40 minutes. Saline placebo infusions will be given every other day until either the subject reports clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal for three consecutive pre-infusion ratings, or a maximum of six infusions have been given over the course of 2 weeks, or they have been discharged from the inpatient unit.; Behavioral: CAMS Therapy; CAMS weekly sessions will also be started immediately as an inpatient at the start of the study while receiving ketamine or saline. CAMS will be continued weekly after the patient is discharged and followed up as an outpatient. Weekly CAMS sessions will be terminated after the subject, as an outpatient, has a clinician rated Scale for Suicidal Ideation (SSI) score of<4, and >50% decrease from baseline, and clinical assessment of patient not being suicidal, for at least 3 consecutive sessions of CAMS.

Outcome Measures

Primary Outcome Measures :

1. Rate of remission of suicidal symptoms at the end of treatment. [ Time Frame: Up to 3 months post-discharge ]
   Remission of suicide symptoms will be defined by a 50% or greater reduction in the clinician-rated baseline Beck Scale for Suicidal Ideation (SSI) score, and SSI score less than the score of 4. SSI scores can range from 0 to 38, and a higher score indicates increased severity of suicidal ideation. The primary outcome of the remission rate will be compared between the two groups.

Secondary Outcome Measures :

1. Number of CAMS sessions needed to achieve enduring mental state [ Time Frame: Up to 3 months post-discharge ]
   Number of CAMS sessions needed to achieve enduring mental state
2. Change of Beck Scale for Suicide Ideation score will be analyzed [ Time Frame: Up to 3 months post-discharge ]
   Change of Beck Scale for Suicide Ideation (SSI) score will be analyzed. SSI scores can range from 0 to 38, and a higher score indicates increased severity of suicidal ideation.

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 24 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subjects must be 15 to 24 years of age
• Subjects must have been admitted to the hospital inpatient unit after a suicide attempt (any intentional, non-fatal self- injury regardless of medical lethality, if intent to die was indicated) and continued to express suicidal ideation. Also at time of screening clinician rated Scale for Suicidal Ideation (SSI) score should be ≥6.
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Subjects with known history of autistic spectrum disorder; non-verbal patients.
• Subjects with moderate or severe intellectual disability (IQ less than 70 and those patients in special education full-time).
• Subjects with schizophrenia or history of any type of psychosis including mood disorder related psychosis and brief reactive psychosis.
• Subjects diagnosed with cluster B personality disorder e.g.borderline personality
• Subjects with a history of recurrent self-harm gestures or self-mutilating behaviors without suicidal intent as judged by psychiatrist
• Within 6 months before initial screening, urine toxicology positive for phencyclidine, cocaine or amphetamines
• Subjects with history of moderate or severe substance or alcohol use per DSM- V criteria in the past 6 months.
• Subjects with any contraindication to ketamine such as allergic reaction to ketamine or medical or neurological condition with a contraindication for use of ketamine or on any drugs associated with significant interaction with ketamine.
• Subjects with BMI > 30 as ketamine is given by weight and high doses of ketamine need to be avoided.
• Subjects who are currently pregnant and/or breast feeding.

Contacts and Locations

Contacts

Contact: Christina Deisz; (440) 225-6193; allync@ccf.org

Contact: Tatiana Falcone, M.D.; (216) 444-7459; falcont1@ccf.org

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02115

Contact: Amit Anand, M.D. 617-732-6753 aanand7@bwh.harvard.edu

United States, Ohio

The Cleveland Clinic

Cleveland, Ohio, United States, 44195

Contact: Tatiana Falcone, M.D. 216-444-7459 falcont1@ccf.org

Sponsors and Collaborators

Tatiana Falcone, MD

National Institutes of Health (NIH)

National Institute of Mental Health (NIMH)

Massachusetts General Hospital

Investigators

• Principal Investigator: Tatiana Falcone, M.D.; The Cleveland Clinic
• Principal Investigator: Amit Anand, M.D.; Massachusetts General Hospital

More Information

• Responsible Party: Tatiana Falcone, MD, Staff, Cleveland Clinic, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT04763343
• Other Study ID Numbers: 21-154; 1R01MH125214-01 ( U.S. NIH Grant/Contract )
• First Posted: February 21, 2021
• Last Update Posted: February 22, 2022
• Last Verified: February 2022

• 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

Additional relevant MeSH terms:

Suicide; Suicide, Attempted; Self-Injurious Behavior; Behavioral Symptoms; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action