A Novel Posttraumatic Stress Disorder Treatment for Veterans With Moral Injury
Phase: NA
Conditions: Moral Injury
Sponsor: VA Office of Research and Development

Official Title: A Novel Posttraumatic Stress Disorder Treatment for Veterans with Moral Injury  
 
NCT Number: 03764033 
 
Document Date: 10/23/2025 
 
 

Study Protocol 
 
Background: The prevalence of PTSD is estimated to be 12-15% in returning combat 
veterans,1-3 and PTSD is now the most common mental health diagnosis among the youngest 
generation of veterans who use Veterans Health Administration care (55%),4 Furthermore, 
veterans that have experienced trauma related to killing in war have high rates of suicide and 
more severe PTSD symptoms than those reporting other types of trauma(s).5-7 As a result of 
killing in war, individuals may experience moral injury, which is defined as, “perpetrating, failing 
to prevent, bearing witness to, or learning about acts that transgress deeply held moral beliefs 
and expectations.”8 A recent study found that PTSD and moral injury were distinct constructs 
with unique signs and symptoms,7 and preliminary evidence indicates that the feelings of guilt 
and anger that characterize moral injury associated with killing may contribute to worsening 
symptoms over the course of existing treatments for PTSD.9 For these reasons, the 
development of targeted moral injury interventions is critical.    
 
We have developed a treatment for moral injury called Impact of Killing (IOK), that is based on 
focus groups, quantitative studies, a moral injury framework, interviews with clinicians, and 
consultation with PTSD experts.10  In our randomized, controlled pilot trial of IOK in veterans with 
PTSD, we found that compared to the wait-list control group, the IOK group experienced a 
significant improvement in PTSD symptoms, general psychiatric symptoms, and quality of life 
functional measures. 10    
 
Objectives: The first aim of this project was to assess the efficacy of an individual treatment for 
PTSD stemming from moral injury called IOK. The primary outcome measure assessed self-
reported psychosocial functioning (World Health Organization Quality of Life-BREF; WHOQOL-
BREF).11 The secondary outcome measures examined clinician-assessed PTSD severity 
(Clinician Administered PTSD Scale for DSM-5; CAPS-5)12 and self-report measures of PTSD 
(PTSD Checklist for DSM-5; PCL-5)13, guilt (Trauma-related Guilt Inventory; TRGI)14, and other 
mental health symptoms (Brief Symptom Inventory; BSI).15 Our second aim was to determine 
whether IOK gains made by veterans in treatment were durable, as measured by a six-month 
follow-up assessment of the self-report outcomes (i.e., WHOQOL-BREF, PCL-5, TRGI, and 
BSI). 
 
Design: The study was a parallel design, randomized, controlled trial to test the efficacy of IOK, 
compared to a present-centered therapy (PCT) control condition. PCT has been used as a 

comparison treatment in prior PTSD research trials.16 To evaluate the durability of IOK gains, 
veterans also participated in a six-month follow-up visit to complete primary and secondary self-
report outcome measures.     
 
Methods: The study was managed by the principal investigator and research staff at the San 
Francisco VA Health Care System (SFVAHCS) and all recruitment, screening and data 
collection procedures were conducted by researchers at the James J. Peters VA Medical Center 
(JJPVAMC) in the Bronx, NY or the Durham VA Medical Center (DVAMC) in Durham, NC.  
Veterans between 18-82 years of age living in the continental U.S. were recruited through direct 
mailings, advertisements, and referrals from VA clinicians or other VA research studies. 
Interested veterans participated in an initial brief phone screen to ensure they met preliminary 
criteria. Those who passed the phone screen were invited to an in-person or video appointment 
to learn more about the study and complete consent procedures prior to additional screening. 
Participants completed demographic and medical history questionnaires, and a clinician-
administered, mental health diagnostic interview (Structured Clinical Interview for DSM 5 [SCID-
5]17 and CAPS-5). These diagnostic interviews were repeated at post-treatment. Veterans that 
passed the diagnostic interview were randomized to treatment. Study clinicians were clinical 
staff at one of the three study sites (SFVAMC, JJPVAMC, DVAMC).     
 
A total of 100 veterans with moral injury were randomized 1:1 to either the IOK or PCT control 
arm within strata therapist treatment site (one of three locations) within randomly generated 
block sizes (4 and 6). IOK is a ten session individual psychotherapy, with 60- to 90-minute 
appointments conducted in-person or by video. PCT was matched for number and duration of 
treatment sessions. Primary and secondary self-report outcome measures were completed at 
baseline, mid-treatment, post-treatment and at six-month follow-up and the clinician diagnosed 
secondary outcome of PTSD severity (CAPS-5) was completed at baseline and post-treatment. 
 
All participants randomized to treatment were included in the intent-to-treat analyses. Twelve of 
these individuals dropped out during treatment and 88 individuals completed study treatment.  
Of the treatment completers, one individual chose not to complete the self-report measures (i.e., 
WHOQOL-BREF, PCL-5, TRGI, and BSI) at the post-treatment time point and a different 
individual opted out of the post-treatment diagnostic interview (CAPS-5). As such, complete 
data for 87 responses through the post-treatment time point were included in the analyses.   

Further, five of the 88 individuals that completed treatment were lost to follow-up and analyses 
of these data included complete data for 83 participants.   
 
Statistical Analysis Plan:  The primary and secondary outcome variables were analyzed with 
separate linear mixed models on the intent-to-treat sample, with participants as a random effect 
and fixed effects for treatment group (IOK, PCT), time point (baseline, mid-treatment, post-
treatment, six-month follow-up), therapist treatment site (SFVAHCS, JJPVAMC, DVAMC), and 
the group-by-time interaction. Time point was treated as a categorical variable to avoid 
assumptions of linearity or any other functional form for outcome variables over time. Treatment 
effects were defined as the difference between treatment groups at the post-treatment time 
point, after adjusting for therapist site. IOK treatment durability was assessed using simple 
marginal contrasts comparing outcomes at the post-treatment to the follow-up time point.    
 
Results: A total of 100 participants were randomized to study treatment and included in the 
intent-to-treat analysis (IOK=49; PCT=51). Participants ranged in age from 28 to 82 years 
(M=48.4 years); 98% were male (n=98) and 2% were female (n=2); 68% were Caucasian 
(n=68), 25% were Black/African American (n=25), 1% were Asian (n=1), 1% were American 
Indian or Alaska Native (n=1), 4% identified as multiracial or other (n=7), and 1% did not report 
their race (n=1). A total of 19% were Latino/Hispanic (n=19). 
   
Participants randomized to IOK (n=49) reported statistically significant improvement on self-
report measures of PTSD severity (p=.006) and guilt (p=.043) compared to veterans that were 
assigned to PCT (n=51). Furthermore, participants in the IOK arm continued to report greater 
improvement in self-reported PTSD (p=.008) and guilt (p=.028) at the six-month follow-up time 
point relative to the PCT arm. These results indicate that IOK treatment gains seen at post-
treatment were maintained during the follow-up period. Further, veterans in the IOK group 
reported greater improvement in general mental health symptoms at six-month follow-up 
(p=.016) compared to the PCT group. There were no differences between groups on the 
primary (WHOQOL-BREF) or secondary (CAPS-5) outcomes, although both groups improved 
on these measures. 
 
 
 

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