A Novel Cognitive Reappraisal Intervention for Suicide Prevention
Phase: NA
Conditions: Suicide Prevention
Sponsor: Weill Medical College of Cornell University

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PROTOCOL TITLE: A Novel Cognitive Reappraisal Intervention for Suicide Prevention 
 
PRINCIPAL INVESTIGATOR: Dr. Dimitris Kiosses, PhD, Weill Cornell Medicine 
IRB Protocol #: 1603017115 
ClinicalTrials.gov Identifier: NCT03026127 
 
Current Version: 8/6/2018 
 
Prior Version Dates: 
Initial 11/30/2016 
Renewal 9/6/2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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BACKGROUND 
Drawing upon recent advances in affective neuroscience, we developed a novel psychosocial 
intervention called "Cognitive Reappraisal Intervention for Suicide Prevention (CRISP)." CRISP aims to 
improve cognitive reappraisal (i.e. modifying the appraisal of a situation to alter its emotional 
significance) (target), and reduce suicide risk (outcome). Our conceptual framework (model) views 
suicidal ideation and behavior as failed attempts to regulate negative emotions. Thus, by improving 
cognitive reappraisal, a well-documented and effective emotion regulation strategy, we expect to 
reduce suicide risk. Our theory is supported by studies showing that unsuccessful attempts to regulate 
negative emotions and decreased cognitive reappraisal are associated with increased suicidal ideation 
and behavior. Further, our pilot data suggest that CRISP improves cognitive reappraisal and reduces 
suicide risk in middle-aged and older adults after discharge from a hospitalization caused by increased 
suicide risk. We assembled a team with complementary expertise required by this study. Dr. Kiosses 
(Cornell) is the developer of CRISP, Dr. Gross (Stanford) is a leading investigator on emotion regulation, 
and Dr. Hajcak (Stony Brook) is an expert on ERPs. The study is aligned with: a) the National Institute 
of Mental Health's (NIMH) "Strategic Plan for Research", b) "A Prioritized Research Agenda for Suicide 
Prevention: An Action Plan to Save Lives", developed by the National Action Alliance for Suicide 
Prevention, and c) the NIMH Research Domain Criteria (RDoC) initiative. 
 
STUDY DESIGN 
The goal of this two phase (R61 and R33) project is to refine and test a novel emotion-regulation 
based psychosocial intervention designed to reduce suicide risk in middle-aged and older adults (50-90 
years old) who have been discharged after a suicide-related hospitalization (i.e. for suicidal ideation or 
suicide attempt). Suicide rates in this group are alarmingly high, and reducing suicide rates in at-risk 
populations is a major NIMH priority. The R61/R33 mechanism is a new mechanism that funds the first 
two years (R61) and depending on the results, the NIMH may fund the following two years (R33). 
Therefore, the funding of the R33 depends on the R61. We were advised to use one protocol by NIMH as 
we will have one clinicaltrials.com. Not only will the funding depend on the R61 results, but also the R33 
study design will depend on the results from the R61 phase: for example, we don¿t know the exact 
duration of the CRISP intervention (6 or 12 weeks) that we will be using for the R33 phase, because we 
are testing these two durations in the R61 phase; and we don¿t know what ERP task will be the best 
one to use for the R33 phase. As seen in the grant, there is a committee that will decide together with 
the NIMH PO about those choices. Therefore, we do not have the R33 consent form, as we don't know 
the exact design decisions for the R33 phase. However, we are planning to submit an amendment with 
all the R33 IFCs as soon as we get funded for the R33 phase. The aims are described in the document 
attached. R61 SPECIFIC AIMS: The goals of this proof-of-concept phase are to optimize CRISP (Cognitive 
Reappraisal Intervention for Suicide Prevention) and test its engagement with cognitive reappraisal 
(target). Certified social workers will administer 12 weekly sessions of CRISP to 40 middle-aged and 
older adults (50-90 years old) after a suicide-related hospitalization. Research assistants will conduct 

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assessments at study entry (hospital admission), at discharge, and at 6 and 12 weeks post-discharge. 
Our aims are: 1. CRISP optimization: We will select the optimized CRISP dosage (6 or 12-week version) 
that improves cognitive reappraisal. 2. Initial demonstration of target engagement: Participants 
receiving the optimized CRISP dosage will show an improvement in cognitive reappraisal (from 
discharge to end of treatment) as assessed by electrocortical measures (i.e. late positive 
potential, LPP) during a standard pictured-based and our novel idiographic cognitive reappraisal 
paradigm. Go: If we meet Milestone 1 ("Feasibility and acceptability of CRISP") & 2 ("Target 
Engagement"). No-Go: If we fail to meet either Milestone 1 or 2. An experts committee will modify 
CRISP based on R61 results. While the research assistants may be aware of the study aims, we will take 
every reasonable effort to ensure they are not aware of the study hypotheses and Go/No-Go criteria 
in testing these hypotheses. Since this R61 phase is not a randomized controlled trial, but a pilot 
study to evaluate the effect of CRISP on cognitive reappraisal, we want to eliminate bias when the 
research assistants collect the data. However, we understand that we may not be able to always fully 
control it. The external investigators from Stanford University, University of Rochester Medical Center, 
and University of Stony Brook will serve as consultants and will only be involved in the protocol 
design and Dr. Hajcak from Stony Brook will also be involved in the statistical analyses of de-
identified data. As they are not receiving funds or engaging in the actual research, no IRB is needed from 
these institutions, which has been confirmed. Please see attachments for continuation of NTRP study 
design regarding audio tapes. 
R61 SPECIFIC AIMS: The goals of this proof-of-concept phase are to optimize CRISP (Cognitive 
Reappraisal Intervention for Suicide Prevention) and test its engagement with cognitive reappraisal 
(target). Certified social workers will  administer  12  weekly  sessions of CRISP to 40 middle-
aged and older adults (50-90 years old) after a suicide-related hospitalization. Research assistants, 
unaware of the study aims, will conduct assessments at study entry (hospital admission), at 
discharge, and at 6 and 12 weeks post-discharge. Our aims are: 1. CRISP optimization: We will select 
the optimized CRISP dosage (6 or 12-week version) that improves cognitive reappraisal. 2. Initial 
demonstration of target engagement: Participants receiving the optimized CRISP dosage will show an 
improvement in cognitive reappraisal (from discharge to end of treatment) as assessed by electrocortical 
measures (i.e. late positive potential, LPP) and self-reported affect during our a standard pictured-based 
and our novel idiographic cognitive reappraisal paradigm. Go: If we meet Milestone 1 ("Feasibility and 
acceptability of CRISP") & 2 ("Target Engagement"). No-Go: If we fail to meet either Milestone 1 or 2. 
An experts committee will modify CRISP based on R61 results. R33 SPECIFIC AIMS: The R33 phase aims to 
provide further evidence of target engagement of the optimized CRISP in a larger sample, evaluate the 
relationship of cognitive reappraisal with suicide risk as measured with Columbia Suicide Severity Rating 
Scale-C-SSRS, and estimate implementation parameters for a large-scale clinical trial. A different sample 
of 75 middle-aged and older adults (using the same inclusion/exclusion criteria as for the R61 phase) 
will be randomized (2 to 1) to CRISP (N=60) or to Supportive Therapy (ST, a control treatment not 
designed to improve emotion regulation) (N=30). Assessments will be conducted on admission, at 
discharge, and at 6, 12, and 24 weeks post-discharge. Primary Aims: 1. CRISP participants will show an 

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improvement in cognitive reappraisal from discharge to the end of treatment. 2. Improvement in cognitive 
reappraisal in CRISP participants will be associated with reduced suicide risk over 24 weeks.  
 
R33 Secondary Aim: Assessment of feasibility and acceptability of ST. Exploratory Analyses: 1. 
Obtain preliminary estimates of treatment eﬀects (CRISP vs. ST) on cognitive reappraisal and on 
suicide risk over 24 weeks. 2. Does the relationship of cognitive reappraisal with suicide risk in 
CRISP participants diﬀer by demographic variables (age, gender), discharge clinical 
characteristics (e.g., depression, executive functioning), types of pharmacotherapy (e.g. 
antidepressants, mood stabilizers) and frequency of utilization of cognitive reappraisal 
techniques (e.g. MindMe tablet app)? 
 
The total number of subjects for the R61 and R33 phases are: 40 for the R61 and 
90 for the R33 phase. DATA ANALYSIS: R61 Phase: Preliminary Analyses: For each variable, we will 
examine the distribution, outliers and abnormal values using graphical methods, e.g., the box-plot. If 
distribution assumptions are violated, we will use transformations or bootstrapping. Primary Aims: 1. 
CRISP optimization: We will select the optimized CRISP dosage (6 or 12-week version) that improves 
cognitive reappraisal. We will consider improvement in LPP and self-report measures from discharge to 
the end of treatment (6 vs. 12-week) as our target engagement outcomes. We will test the two 
dosage with an intent-to-treat (ITT) principle and perform t-tests or linear regression (with covariates) to 
test the between-group difference. If distributional assumptions are violated, their non-parametric 
counterpart or bootstrapping will be used. Dosage Optimization Decision: The decision will be made 
by the Experts Committee after taking into account both quantitative findings (a statistical 
comparison of target engagement between the two dosages; the effect sizes of each dosage at 
end of treatment) as well as qualitative factors including feedback from patients and therapists. Aim 2. 
Initial demonstration of target engagement: Participants receiving the optimized CRISP dosage will 
show an improvement in cognitive reappraisal (from discharge to end of treatment) as assessed by 
electrocortical measures (i.e. late positive potential, LPP) during a standard pictured-based and our 
novel idiographic cognitive reappraisal paradigm. We will obtain the standardized effect size for both 
measures of improvement in  cognitive  reappraisal.  R33 Phase: Preliminary Analyses: For each 
variable, we will examine the distribution, outliers, and abnormal values using graphical methods, e.g., the 
box-plot. If distribution assumptions are violated, we will use transformations or bootstrapping. Primary 
Aims: Aim 1. CRISP participants will show an improvement in cognitive reappraisal from discharge 
to the end of treatment. The analytic plan will be similar to R61 Aim 2, but conducted in a larger 
sample. Aim 2. Improvement in cognitive reappraisal in CRISP participants will be associated with 
reduced suicide risk over 24 weeks. We will first use a generalized mixed effects regression model to 
analyze C-SSRS as a dependent variable over multiple assessment points and with improvement in 
cognitive reappraisal measures considered as an independent variable. We will test several distributions 
and corresponding link functions (e.g. Poisson distribution, normal distribution or binomial (Low vs High 
suicide risk, based on C-SSRS scores)) in this generalized linear mixed model. We will chose the best 
fitting model using Bayesian Information Criterion. Secondly, we will perform a survival analysis in CRISP 
participants to model time to event in a Cox proportional hazard model. The time to event will be based 

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on C-SSRS [Event=active suicide ideation with any methods (C-SSRS greater or equal to 3); or suicide-
related hospitalization; or an attempt (actual, interrupted, or aborted)]. In two separate models, we will 
include the two measures of improvement of cognitive reappraisal from discharge to end of treatment 
(LPP and self-report affect) as dependent variable. We will test violations of proportional hazard 
assumptions using Schoenfeld's residual and by graphical techniques. We will focus on magnitude of 
effect following McGough and Faraone[98] rather than significance testing. Secondary Aim: Assessment 
of feasibility and acceptability of ST. Feasibility of ST: At least 80% of ST participants will either 
complete ST or discontinue treatment because of an adverse outcome. Acceptability of ST: We will 
obtain an average Treatment Satisfaction score &#8805; 3 (out of 4) at the end of ST. .... 
 
INCLUSION AND EXCLUSION CRITERIA 
Inclusion Criteria: 
1. Age: 50 years and older. 2. Diagnosis (based on SCID-5 Clinical Trials Version to assess DSM-5 
diagnoses): Any DSM-5 depression or anxiety diagnosis, including major depressive disorder, 
bipolar depression, depressive disorder Not Elsewhere Classified, anxiety disorder Not 
Elsewhere Classified, adjustment disorder with anxiety and depressed mood (but without any of 
the diagnoses shown under Exclusion criteria). 3. Recent hospitalization for suicidal ideation or 
suicide attempt; at hospital admission, Columbia Suicide Severity Rating Scale greater or equal 
to 3, “Active Suicide Ideation with any methods or a suicide attempt”. 4. Patients with any degree of 
suicidal ideation at discharge (Columbia Suicide Severity Rating great or equal to 0) will be included. 5. 
We will also include patients on psychotropics and on after-care community psychotherapy. 
 
Exclusion Criteria: 
1. History or current diagnosis of Psychotic Disorders; Current Diagnosis of Bipolar I or 
Bipolar II, with current episode hypomanic, manic or mixed; Diagnosis of Dementia. 
2. Cognitive Impairment: We will exclude participants with Mini Mental State Exam 
less than 24. 3. Acute or severe medical illness (i.e., delirium; decompensated cardiac, 
liver or kidney failure; major surgery; stroke or myocardial infarction during the three 
months prior to entry). 4. Aphasia, sensory problems, and/or inability to speak English. 
 
 
DATA AND SAFETY MONITORING PLAN 
The study will help this population who has suicide ideation to monitor their depression, their 
suicide ideation, and emotion regulation through weekly therapy sessions and research 
assessments. The therapy will have 12 weekly sessions during which the therapists will evaluate 
these. In addition, the research assessments will be conducted at admission, discharge, week 6, 

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and week 12 (end of treatment). If the patient has any suicide ideation, the research assistant 
will complete the Suicide Risk Assessment Protocol. The PI will be available 24 hours a day to 
speak with therapists, research assistants, and patients to ensure appropriate actions in case 
of suicide ideation. Participants will have Dr. Kiosses's cell number (in the informed consent) 
to call 24 hours a day and they will be asked to contact him if there is any increase in suicide 
ideation. The Suicide Risk Assessment (attached) has been approved by NIMH for determining 
an increase in suicidal ideation, is completed by the research assistant, and reviewed 
immediately by the PI or another psychologist, either in person or over the phone. Depending 
on the level of risk, the subject will be encouraged to speak to his/her own clinician; the PI or 
therapist may call the subject's clinician and/or family member; the subject may be referred 
for an evaluation by a psychiatrist present in the office at the time, or the subject may be escorted to 
the evaluation center at NYPH to possibly be hospitalized. Other urgent risks may necessitate calling 
911 or having a family member bring the subject to a local emergency room for evaluation (if 
subject is being interviewed over the phone, for example). This protocol has been successfully 
used in other protocols at our Institute. This Suicide Risk Assessment will be administered to all 
subjects during the weekly phone meeting, and the action plan will be followed as stated, after 
being reviewed by the PI or another psychologist at the Institute: if there is a mild risk, it will be 
recommended that the subject speak to their clinician. If there is more than a mild risk of SI, the 
PI or on-call psychologist may speak with the subject over the phone and take appropriate 
clinical action. This may include calling 911 or having a family member or caregiver bring the 
subject to a local emergency room. A referral to an external mental health referral will be 
oﬀered to subjects: a) who withdraw from the study in the event of personal distress, and b) 
after the subjects complete the 12 week treatment.  
 
The study will use the adverse event grading guidelines provided by WCMC's Oﬃce of Research 
Integrity and Assurance. All adverse events will be reported to the WCMC IRB in the timeline 
indicated by the WCMC Human Research Protections Program Immediate Reporting Policy. Plan 
for Grading Adverse Events. Adverse event (AE): An adverse event (AE) is any adverse change 
from the participant¿s baseline condition, regardless of relationship to the study intervention 
which occur after informed consent is signed. Adverse events include but are not limited to: (1) 
worsening or change in nature, severity, or frequency of conditions or symptoms present at the 
start of the study; (2) participant deterioration due to primary illness; and (3) intercurrent illness. 
Following questioning and evaluation, all AEs, whether determined to be related or unrelated 
to the study psychosocial intervention by the Site Protocol Principal Investigator, must be 
documented in the participant¿s medical records, in accordance with the investigator¿s normal 
clinical practice. Each AE is evaluated for duration, severity, seriousness, and causal 
relationship to the study intervention. Serious Adverse Event (SAE): Any untoward medical 
occurrence that: results in death, is life-threatening, require inpatient hospitalization or 
prolongation of existing hospitalization, results in persistent or signiﬁcant disability/incapacity, 
or is a congenital anomaly/birth defect (NIH Guide-6/11/99). Note 1: Medical and scientiﬁc 
judgment should be exercised in deciding whether expedited reporting is appropriate in other 

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situations, such as important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the subject or may require intervention to 
prevent one of the outcomes listed in the deﬁnition above. Note 2: Hospitalizations that fulﬁll 
one of the following conditions will not have to be reported as SAE: 1. Hospitalizations for social 
reasons and thus unrelated to a deterioration of the subject¿s condition or adverse event (e.g., 
deterioration of the living conditions related to environmental factors rather than to a 
deterioration of the disease, lack of transportation to the investigational site, respite care for 
the caregiver) 2. Hospitalizations for elective surgical interventions for which the date had 
already been determined prior to the study participation. Attribution of Adverse Events. 
1. Deﬁnite: Adverse event(s) will clearly be related to the intervention and cannot be 
reasonably explained by an alternative explanation. 2. Probable: Adverse event(s) will 
likely be related to intervention. 3. Possible: Adverse event(s) may be related to the 
intervention. 4. Unlikely: Adverse event(s) will doubtfully be related to the intervention. 
5. Unrelated: Adverse event(s) will clearly not be related to the intervention. 
Adverse events will be reported to the WCMC IRB as per WCMC AE reporting policy. We will 
submit individual adverse events, as well as summary tables every six months to the DSMB, but 
we would respond to the DSMB recommendation if a higher frequency of reporting is desirable. 
This is a talk therapy study which does not involve medications or medical devices. 
No interim analyses of the outcomes will be performed as that may affect the remaining part of the 
study.