Ketamine For Suicidal Ideation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Mount Sinai School of Medicine
Sponsor:
Information provided by (Responsible Party):
James Murrough, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01507181
First received: January 6, 2012
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

This study will examine the effects of Intravenous (IV) ketamine both in an outpatient population and with subjects on the inpatient unit with suicidal ideation (SI).


Condition Intervention Phase
Suicidal Ideation
Drug: Ketamine
Drug: Midazolam
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigating Rapid Anti-Suicidal Ideation Effects of Intravenous (IV) Ketamine in Hospitalized Patients

Resource links provided by NLM:


Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:
  • Change in Beck Scale for Suicidal Ideation (BSSI) [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide.

  • Change in Beck Scale for Suicidal Ideation (BSSI) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: No ]
    Beck Scale is a 21-item self or clinician administered instrumentation used to measure the current intensity of patients' specific attitudes, behaviors and plans to commit suicide.


Secondary Outcome Measures:
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: No ]
    The MADRS is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms.

  • Patient Rated Inventory of Side Effects (PRISE) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: Yes ]
    The PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other)

  • Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: Yes ]
    a comprehensive, semi-structured interview measure that uniquely measures the full spectrum of suicidality including passive and active suicidal ideation, suicidal intent as well as suicidal behaviors

  • The Young Mania Rating Scale (YMRS) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: Yes ]
    an 11-item questionnaire, used to assess manic symptoms based on the patient's subjective report of his or her clinical condition

  • The Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: Yes ]
    to assess acute behavioral changes during the infusions

  • The Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: 24 hours post infusion ] [ Designated as safety issue: Yes ]
    to measure dissociative effects during the infusions


Estimated Enrollment: 24
Study Start Date: January 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ketamine
single dose IV ketamine, .5mg/kg
Drug: Ketamine
single dose IV ketamine, .5mg/kg infused over 40 minutes
Other Name: N-methyl-D-aspartate (NMDA) glutamate receptor antagonist
Placebo Comparator: Midazolam
single dose IV midazolam, .45mg/kg
Drug: Midazolam
single dose IV midazolam, .45mg/kg infused over 40 minutes

Detailed Description:

Depression is a debilitating disorder that affects 12-20% of population and is among the top five leading causes of burden of disease worldwide (Kruijshaar ME 2005). Suicide associated with depression and other psychiatric disorders is a pervasive public health problem and results in almost one million deaths per year. Unfortunately, current treatments for severe depression have limited efficacy for suicidality, specifically due to the slow time course of change in suicidal thoughts. Recently ketamine, a glutamate-modulating agent, was shown to have antidepressant and anti-suicidal effect in outpatient depressed patients. The proposed study will test the ability of a single sub-anesthetic intravenous (IV) dose of the glutamate NMDA receptor antagonist, ketamine, to provide rapid decrease in suicidal ideation (SI) in patients hospitalized with SI. In this randomized parallel-arm placebo controlled trial, ketamine is compared to midazolam, which is expected to mimic some of the acute subjective effects of ketamine but not have any sustained antidepressant effects.

Specific Aim 1: To determine feasibility and tolerability of a single low-dose IV infusion of ketamine in patients with prominent SI and elevated risk for suicide.

Hypothesis 1: Ketamine administration will be feasible and well tolerated in patients admitted to a psychiatric hospital with SI.

Specific Aim 2: To test the efficacy of a single IV dose of ketamine, compared to an anesthetic control condition (midazolam), to rapidly reduce SI in a controlled hospital setting.

Hypothesis 2: Ketamine will be associated with significant and rapid reductions in SI and depressive symptoms within 24 hours.

This study will test the rapid anti-suicidal effect of a single IV dose of the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine in suicidality compared with the clinical response to a single IV dose of the short-acting benzodiazepine midazolam. Midazolam is able to induce transient neuropsychiatric effects mimicking ketamine and therefore is expected to protect the integrity of the blind. Participants will continue to receive standard treatment for their psychiatric condition throughout the trial. This unique "proof-of-concept" study in suicidal patients will be conducted over three-year period.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • English speaking Male or female patients, 18-80 years
  • Patients have voluntarily admitted themselves to an inpatient psychiatric unit at MSH or, regarding the outpatient population, have clinically significant suicidal ideation without intent to harm themselves
  • Women of childbearing potential must have a negative pregnancy test
  • Clinically significant suicidal ideation and score of ≥4 on MADRS item 10 for suicidality
  • Each subject must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document

Exclusion Criteria:

  • Lifetime history of schizophrenia or other primary psychotic disorder
  • Current presence of psychotic symptoms
  • Lifetime history of a clearly established psychotic episode
  • Established diagnosis of Schizoid, Schizotypal or Paranoid personality disorder
  • Urine toxicology screen positive for drugs of abuse on admission
  • Substance abuse or dependence within the preceding 1 month
  • Anticipated discharge within 7 days of study enrollment (for patients in the inpatient arm)
  • Women who plan to become pregnant, are pregnant or are breast-feeding
  • Concurrent course of electroconvulsive therapy (ECT)
  • Any unstable medical illness including hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease
  • Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG
  • The presence of any known or suspected contraindications to midazolam or ketamine including, but not limited to, known allergic reactions to these agents or acute intermittent porphyria
  • Uncontrolled hypertension, defined as BP systolic >160 or BP diastolic >100 on medications
  • Arrhythmia requiring medication
  • Severe coronary artery disease, defined as Canadian Cardiovascular Status III or IV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01507181

Contacts
Contact: Kaitlin DeWilde 212-241-7906 kaitlin.dewilde@mssm.edu
Contact: Laili Soleimani, MD laili.soleimani@mssm.edu

Locations
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10027
Contact: Kaitlin DeWilde    212-241-7906    kaitlin.dewilde@mssm.edu   
Contact: Laili Soleimani, MD       laili.soleimani@mssm.edu   
Principal Investigator: James Murrough, MD         
Sponsors and Collaborators
James Murrough
Investigators
Principal Investigator: James Murrough, MD Mount Sinai School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: James Murrough, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01507181     History of Changes
Other Study ID Numbers: GCO 10-1589
Study First Received: January 6, 2012
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:
suicidal ideation
major depression
treatment resistant
ketamine
glutamate

Additional relevant MeSH terms:
Suicidal Ideation
Suicide
Self-Injurious Behavior
Behavioral Symptoms
Ketamine
Excitatory Amino Acid Antagonists
Midazolam
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
GABA Modulators
GABA Agents

ClinicalTrials.gov processed this record on September 18, 2014