Clinical trial NCT02418702: A Study to Decrease Suicidal Thinking Using Ketamine
Official title: A Randomized Controlled Trial to Decrease Suicidal Thinking Using Ketamine
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Depression
Suicide
Keywords: depression
suicide
ketamine
rapid intravenous bolus
sub-anesthetic dose
double-blind placebo control
Lead sponsor: United States Naval Medical Center, San Diego
Sponsor class: FED
First posted: 2015-04-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Depression treatment typically is slow acting. Patients presenting with acute suicidality have few immediate treatment options. However, sub-anesthetic doses of ketamine have been now widely tested as a rapid-acting treatment for depression. Gregory Larkin et al at Yale showed this could be applied to suicidal patients, with 14 of 15 participants showing remission of suicidal thinking within 40 min of the administration of ketamine, with 13 showing lasting remission out to 10 days. No serious side effects were reported. This project proposes to conduct a randomized, placebo-controlled trial of this, same intervention in military patients recently hospitalized for suicidal thinking. After being assessed, and giving informed consent, participants would receive 0.2mg/kg ketamine or placebo. Their suicidal thinking, depression, and other symptoms would be monitored acutely for 240 min after drug infusion, and the for lasting changes the next day, at hospital discharge, 2 weeks, and 10 weeks. Potential adverse events will be monitored via the electronic medical record for up to a year.

Detailed description: Patients presenting for acute suicidality have few immediate treatment options to alleviate their suffering aside from psychiatric hospitalization for safety assurance. Therapy and psychiatry medication may decrease depression over time, but this does little to improve depression and suicidal thinking in the short term. Preliminary data from a recent study by Larkin et al at Yale University showed evidence to support a promising novel treatment modality with rapid effects on suicidal ideation for up to 10 days post infusion through the use of a single sub-anesthetic rapid intravenous bolus dose of ketamine (0.2-mg/kg) administered in the acute Emergency Department setting. This study showed favorable evidence to support further investigation into the use of a single sub-anesthetic bolus dose of ketamine in acutely depressed and/or suicidal patients in the emergency room setting. Based on the success of this study, Naval Medical Center San Diego (NMCSD) started the previously mentioned, small, unfunded randomized, placebo-controlled trial of this ketamine protocol for patients who were pending psychiatric hospitalization because of suicidal thinking. Data collection was highly flawed, but unpublished, preliminary results show that the ketamine treatment resulted in significant decreased in suicidal thinking.

Of note, there were no adverse events associated with the ketamine administration. Although the infusion was done in an Emergency Department (ED) setting, the patients were seated in clinic chairs, and required no additional monitoring or intervention beyond what could be provided in any clinic our psychiatric hospital setting. It is the intent of the project to expand on our unfunded trial, allowing us to treat a wider range of participants who come in to the psychiatric ward because of suicidal thinking. This study is being pursued in the context that existing therapies for major depression have a lag of onset of action of several weeks, resulting in an increased risk of possible and considerable morbidity and possibly mortality through suicide. This study would explore the efficacy of Ketamine's (a N-Methyl-D-aspartate (NMDA) receptor antagonist) rapid and potentially long-lasting antidepressant effects in a suicidal population. The Investigators hope to gather data that could potentially impact treatment practices in the military setting for acutely depressed patients. This may potentially shorten, delay, or even forgo admissions to the psychiatric ward in the future, as well as potentially reducing the long term suicidality.

Eligibility criteria: Inclusion Criteria:

* Voluntarily, psychiatrically hospitalized at NMCSD within the last 12 hours for suicidal thinking
* BSS greater than 4
* BHS greater than 8
* BDI greater than 19
* Ability to give informed consent
* Active duty military status
* Verified negative pregnancy test for females

Exclusion Criteria:

* Psychosis or bipolar disorder
* Pregnancy
* Involuntary status on presentation to the ED
* Positive for illicit drugs of abuse
* Blood alcohol level greater than zero
* Previous enrollees in this treatment protocol will be excluded from repeat participation
* Any patient brought for command directed psychiatric evaluation
* Specific contraindication to the use of ketamine are as follows and under such circumstances or conditions, personnel with the following should be excluded from participation in this study:

A) patients with elevated intracranial pressure, uncontrolled hypertension, coronary artery disease, aneurysms, thyrotoxicosis, congestive heart failure (CHF), a recent history of head or eye injury, or angina B) all personnel in whom a significant elevation of blood pressure would constitute a serious hazard to their overall health and well-being C) patients currently utilizing the following medications: conivaptan, dasatinib, peginterferon alfa-2b, quazepam, tocilizumab

Primary outcomes:
measure: Change in baseline in depressive symptoms measured by Beck Scale for Suicide ideation (BSS), Beck Hopelessness Scale (BHS), and Beck Depression Index (BDI)
timeFrame: baseline and 240 minutes
measure: Change in baseline in depressive symptoms measured by Beck Scale for Suicide ideation (BSS), Beck Hopelessness Scale (BHS), and Beck Depression Index (BDI)
timeFrame: baseline and 2 weeks
measure: Change in baseline in depressive symptoms measured by Beck Scale for Suicide ideation (BSS), Beck Hopelessness Scale (BHS), and Beck Depression Index (BDI)
timeFrame: baseline and 10 weeks
Secondary outcomes:
measure: Reduction in suicidal thinking measured by BSS, BHS, and BDI
timeFrame: 1 day post-infusion
measure: Reduction in suicidal thinking measured by BSS, BHS, and BDI
timeFrame: 2 weeks post-infusion
measure: Reduction in suicidal thinking measured by BSS, BHS, and BDI
timeFrame: 10 weeks post-infusion
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Naval Medical Center San Diego
state: California
Study officials:
affiliation: United States Naval Medical Center, San Diego
name: Marc A Capobianco
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000 Feb 15;47(4):351-4. doi: 10.1016/s0006-3223(99)00230-9.
citation: Panzer O, Moitra V, Sladen RN. Pharmacology of sedative-analgesic agents: dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists. Crit Care Clin. 2009 Jul;25(3):451-69, vii. doi: 10.1016/j.ccc.2009.04.004.