Clinical trial NCT04154150
Conditions: Suicide, Attempted
Sponsor: Rebecca Price
Start date: 2019-12-19; Completion date: 2022-03-15
Enrollment: 16 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This project seeks to identify the acute and longer-term impact of a single dose of intravenous ketamine among suicidal patients referred for psychiatric consultation/liaison in the medical inpatient setting. The investigators will then test whether ketamine's rapid effects can be extended by introducing helpful information delivered by a computer-based training protocol. This work could ultimately lead to the ability to treat suicidality more efficiently and with broader dissemination by rapidly priming the brain for helpful forms of learning.

Detailed description:
NOTE: In the course of this pilot study, both the primary and secondary outcome measures were supplemented to provide additional, complementary information on the clinical effects of the study interventions, based on confirmation (through study team experience) of the feasibility of acquiring such additional information in the context of our study population, setting, and design.

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Intravenous ketamine intervention 2: Cognitive training intervention 3: Sham Training
Intervention descriptions: intervention 1: Single subanesthetic infusion of ketamine (0.5mg/kg) intervention 2: 8 sessions of computer-based cognitive training intervention 3: 8 sessions of computer-based sham training

Protocol documents:
Prot_SAP_000.pdf: 
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Study Protocol  
 
 
 
 
 
 
Official Title: Ketamine + Cognitive Training for Suicidality in the 
Medical Setting: Pilot 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT04154150 
 
 
 
Protocol Date: 01/03/2020 
 
 
 
 


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Scientific Background 
Rapidly acting pharmacological agents, such as subanesthetic ketamine, 
offer the promise of a new opportunity to address suicidal crises with the 
urgency they require, but this promise remains unfulfilled to date. 
Ketamine rapidly reduces suicidal thoughts as early as 2-24 hours after a 
single infusion, both in depressed patients and in transdiagnostic patients 
selected for high suicide risk, with some evidence suggesting effects on 
suicidality are statistically independent of antidepressant effects. Yet, a 
significant barrier to clinical adoption of this treatment approach is the 
lack of evidence for durability of these effects, raising concerns about 
illusory recovery and subsequent rebound of suicidality. Even if safe, 
effective pharmacological strategies to sustain ketamine’s rapid effects 
are identified, the majority of depressed patients express preference for 
treatments involving a behavioral/learning component (e.g., up to 91% 
enrolling in drug trials. 
 
Practical challenges in maintaining drug regimens over time further 
suggest that a diversity of approaches to achieve rapid, durable relief is 
likely to benefit the field; but efforts to extend ketamine’s rapid effects 
nonpharmacologically remain in early stages. 
In the proposed effectiveness pilot RCT, we posit that intravenous 
ketamine will induce a rapid shift towards greater plasticity and 
cognitive flexibility among patients with a recent suicide attempt, which 
can then be exploited in order to consolidate adaptive 
learning while neuroplasticity remains high. At the molecular level, 
depression and suicidality have been characterized as failures of 
neuroplasticity, including neuronal atrophy and synaptic depression in 
the prefrontal cortex (PFC) and hippocampus. At the neurocognitive 
level, suicidality is marked by impairments in experience-based 
learning, decision making, cognitive flexibility, and prefrontal 
inhibition, leading to inflexible negative biases in cognition and 
behavior, such as rigidly held “depressive selfschemas” 
(negative representations of self), a key risk factor for depression. 
Ketamine is posited to reverse the molecular signature of depression via 


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synaptogenic and neuroplasticity effects at the molecular level. We 
propose to leverage this shift to support adaptive learning. Thus, we 
hypothesize that we can extend and/or enhance rapid relief from 
suicidality during this window of opportunity by reinforcing adaptive 
self-representations through a novel form of cognitive training (CT) 
delivered by laptop computer. The past decade has seen growing interest 
in automated, mechanistic, dissemination-ready CT treatments, designed 
to modulate affective processing patterns directly in order to reduce 
symptoms. Though clinical effects show potential for reducing 
suicidal ideation in high-risk samples, the durability of such effects is 
currently limited. A critical gap in this literature, which this proposal 
will fill, is to initiate CT synergistically during a key clinical window of 
opportunity, when euthymic mood and enhanced plasticity are expected, 
to consolidate beneficial processing patterns and increase and prolong 
ketamine’s rapid anti-suicidal effects. 
 
This project will extend our research program wedding two previously 
unlinked areas of research: rapid pharmacology and automated CT. This 
synergistic approach is ideally suited to reaching individuals at imminent 
risk of suicide who may not otherwise engage effectively with mental 
health care: in this case, medical inpatients referred for psychiatric 
consultation/liaison immediately following a suicidal act. Patients will 
receive all study intervention procedures in a medical inpatient setting 
(e.g., during toxicology stabilization), and then will be followed as 
they transfer to psychiatric inpatient settings (as part of standard care), 
enabling us to quantify the impact of a single ketamine “pretreatment” 
on acute and long-term outcomes following a suicidal crisis. We will 
expand on our previous, replicated findings suggesting ketamine 
promotes rapid decreases in explicit suicidal thoughts, which are further 
linked to rapidly increased plasticity in implicit self-representations. 
In addition, we will pilot test a brief, highly efficient CT intervention 
designed to work synergistically within the brief window of opportunity 
ketamine provides in order to consolidate beneficial self-representations 
while neuroplasticity remains high.  
 


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Study Objectives 
This project seeks to identify the acute and longer-term impact of a 
single dose of intravenous ketamine among suicidal patients referred for 
psychiatric consultation/liaison in the medical inpatient setting. We will 
then explore the feasibility of introducing helpful information delivered 
by a computer-based training protocol, designed to extend ketamine's 
rapid effects. This work could ultimately lead to the ability to treat 
suicidality more efficiently and with broader dissemination by rapidly 
priming the brain for helpful forms of learning. 
 
 
 
 
 
Study Design & Methods 
 
Medical inpatients will be enrolled through the psychiatric 
consultation/liaison service in a large Level 1 trauma hospital. In the 
context of ongoing standard care, participants will be randomized in a 
double-blind, parallel arm design to one of two groups: ketamine 
infusion followed by fully automated, computer-based CT or ketamine 
infusion followed by a sham variant of CT (a computer task that does 
not target suicide-relevant cognition). 
 
 
 
 
Eligibility Criteria: 
Inclusion Criteria: 


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Participants will: 
1. be between the ages of 18 and 65 years 
2. be a medical inpatient referred for psychiatric consultation/liaison due to 
suicidality 
3. possess a level of judgment and understanding sufficient to agree to all 
procedures required by the protocol and must sign an informed consent 
document 
4. be deemed an appropriate and reasonable medical candidate for 
intravenous ketamine by a physician authorized to prescribe medication 
to the patient during inpatient hospitalization 
Exclusion Criteria: 
1. Presence of current psychotic or autism spectrum disorder or current 
delirium 
2. Use of a Monoamine Oxidase Inhibitor (MAOI) within the previous 2 
weeks 
3. Current pregnancy or breastfeeding 
4. Reading level <5th grade as per WRAT-3 reading subtest 
5. Past intolerance or hypersensitivity to ketamine 
6. Patients taking any of the following medications: St John's Wort, 
theophylline, tramadol, metrizamide 
7. Patients who have received ECT in the past 6 months prior to intake 
8. Patients at risk for withdrawal related issues (e.g., delirium tremens, 
severe opiate withdrawal) or who present with substance-induced 
psychosis 
9. Patients who, based on expressed preference and/or home geographic 
location, are deemed by the Psychiatric Consultation/Liaison service to 
be likely to receive inpatient psychiatric hospitalization at an alternate 
location outside of Western Psychiatric Institute & Clinic 
 
 
 
 
Statistical Considerations and Statistical Analysis Plan 
This is a pilot study, designed to develop novel study infrastructure and 
novel intervention methods, leading to small numbers of patients in each 


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treatment arm. Descriptive statistics (means, standard deviations) will be 
reported without statistical analysis to directly compare the two groups 
(active vs. sham CT), given the small number of patients within each 
group, which yields low statistical power for between-group 
comparisons.