Feasibility Study of Compassion Meditation Intervention for Older Veterans in Primary Care With Anxiety or Mood Disorders
Phase: NA
Conditions: Anxiety and Mood Disorders
Sponsor: VA Office of Research and Development

Study Title:   Feasibility Study of Compassion Meditation Intervention for Older Veterans in Primary Care 
with Anxiety or Mood Disorders 
 
NCT #: NCT03964246 
 
Date of Document: 09/21/2020 

Veterans, then there is a unique opportunity for an evidence-based, novel treatment that not only reduces 
psychological distress, morbidity and mortality, but also promotes “healthy aging” and increases well-being 
(Jeste et al., 2015).
 
The proposed feasibility study of a compassion meditation (CM) intervention represents an essential 
foundation for subsequent larger (VA Merit supported) research to investigate CM as a means to address a 
critical unmet need among older Veterans with psychological distress. The feasibility, acceptability, and 
effectiveness of the approach in this population are not yet known, but if successful, then there is high 
potential benefit as an innovative wellness/recovery-focused intervention that has shown benefit for other 
populations. If properly adapted and validated for older Veterans with psychological distress, CM may not 
only reduce mental health symptom severity, but promote positive mental and physical well-being.
 
Fostering recovery through positive/strengths-focused interventions: The goal of VA Rehabilitation 
Research and Development (RR&D) is to maximize functional recovery. In the broader field of mental 
health recovery and rehabilitation, as well as positive psychology and psychiatry, there has been increased 
recognition of the clinical importance of not only treating the primary psychiatric symptoms, but of 
simultaneously building and promoting positive psychological factors, such as compassion, resilience, and 
optimism (Jeste et al, 2015; Seligman, Rashid, & Parks, 2006) A “strengths-based” approach is core to 
most recovery models, i.e. recovery is not limited to symptom management, but focused on fostering a 
return (or enhancement) of functioning and well-being, even in the presence of physical or mental health 
challenges. CM has been shown to be beneficial among (primarily) younger, non-VA, non-clinical samples 
not only in terms of reducing emotional distress, but also in promoting recovery-relevant constructs 
including well-being and positive psychological factors (Kirby, Tellegen, & Steindl, 2017). However, the 
experiences, concerns, and preferences of older Veterans tend to differ in significant ways from their 
civilian counterparts, as well as from younger Veterans; therefore, interventions developed and validated 
in other populations cannot be assumed efficacious for older adults. Thus, the line of research catalyzed by 
the presently proposed feasibility study represents a novel and critical contribution to rehabilitation
/recovery research and Veteran well-being.
 
Compassion meditation (CM): CM is a meditative practice focused on cultivating compassion based on an 
awareness of common humanity out of which is derived a heartfelt wish that the self and others may be 
free of suffering. Prior research in civilian samples has found this type of practice to be associated with 
increases in positive emotion and reductions in perceived stress and negative mood. In Kirby et al.’s 
(2017) recent meta-analysis of compassion interventions, there were moderate effect size improvements 
in negative emotions (anxiety, depression, general psychological distress) and positive emotions and 
outcomes (including self-compassion, compassion for others, and well-being). CM may also improve social 
connection and its associated effects on psychosocial functioning  and may improve self-esteem  and 
health. Although there have been few Veteran-focused studies of CM interventions, two recent small trials 
by Dr. Lang (Co-Investigator for the proposed project) and colleagues found decreased negative emotions 
and increased social connectedness among Veterans with PTSD receiving CM (Lang et al., 2017).
 
Most reported studies of compassion-based interventions have been conducted in non-Veteran, non-older 
adult, and non-clinical samples. Also, the older Veteran population is predominantly male, but with the 
exception of Dr. Lang’s work, samples in the published research have been predominantly female (e.g., 
only 26% of the participants in the studies in Kirby et al.’s (2017) meta-analysis were male). Thus, the 
adaptations required to maximize effectiveness of CM for older Veterans with clinically significant anxiety 
and/or depression, particularly outside the context of PTSD, is presently unknown.
 
Improving acceptance/utilization of positive psychological interventions: Prior research has shown that the 
perceived stigma of mental health concerns is a barrier to mental health treatment seeking and 
acceptance, particularly among older adult (Conner et al., 2010). As CM and other positive psychological 
interventions are more saliently focused on promoting strengths, they may be perceived as carrying lower 
stigma than interventions directly focused on reducing mental health symptoms, such as depression or 
anxiety, and thus may result in higher acceptability and utilization. Previous work suggests the 
acceptability of mindfulness-based intervention for older adults (Geiger et al., 2016; Oken et al., 2017); 
this project will evaluate whether this acceptability generalizes to CM as applied to older psychologically 
distressed Veterans.
 
Biological mechanisms: One of the key national mental health research priorities has been identification of 
biological mechanisms underlying mental health concerns and/or their health consequences and treatment 
effectiveness. Depression, anxiety, and general psychological distress are associated with accelerated 
biological aging, which may in turn be mediated by chronic inflammation or changes in stress-induced 
inflammatory response that are associated with elevated blood-based inflammatory biomarkers (Van der 
Kooy et al., 2007; Vogelzangs et al., 2013,  2016; Wolkowitz et al., 2011). Results from two studies, albeit 
in adolescents or college students, suggest possible reductions in C-reactive protein levels and/or 
interluekin-6 response following a CM intervention. There is also evidence that related component 
practices, such as mindfulness, reduce inflammatory responses (Rosenkranz et al., 2013). In a recent 
comprehensive review, Black & Slavich (2016) found possible effects of mindfulness meditation on 
inflammation, immune function, and biological aging, but also noted the limitations of the existing work 
warrant further research before definitive conclusions can be drawn. This study will provide essential 

Sociodemographic and clinical characteristics: To characterize the sample, baseline measures will include 
age, education, gender, relationship status, medical comorbidity, and active medications, as determined 
through participant interview and/or review of available records in the VA Computerized Patient Record 
System (CPRS).
 
CM intervention: Through the experience and feedback from the three successful CM groups we will adapt 
the CBCT-Vet(Lang et al., 2017)  intervention for use in older adults with anxiety or depressive symptoms. 
This adaptation will be conducted with input from Dr. Negi and Mr. Harrison (developers of CBCT® and 
consultants for the proposed project), and the experience and expertise of the study team.  Expected 
adaptations include changing the focus of examples from PTSD to anxiety and depression, as well as 
adjustments for appropriate use with older Veterans. The CBCT-Vet includes 10 90-minute sessions that 
will be led by Dr. Casmar, a VA Staff Psychologist and Co-Investigator on the proposed project, who is 
certified in CBCT® with significant experience in administering CBCT-Vet. Sessions 1 - 4 assist participants 
in basic mindfulness breathing practices; sessions 4 - 8 focus on personal analysis of factors underlying 
difficulties with compassion for self or others; the final two sessions (9 and 10) review content and assist 
with relapse prevention. Session by session topics are: (1) Introduction and learning breathing meditation, 
(2) Focused attention, (3) Creating space, (4) Mindful awareness, (5) Re-engaging with heroic spirit, (6) 
Seeing ourselves in others, (7) Appreciation and gratitude, (8) Empathy and engaged compassion, (9) 
“Putting it all together,” and (10) “Putting it all together 2.”
Our target is to have 5-8 participants completing each 10-week intervention, thus we will enroll up to 10 
per group to account for possible attrition. Two or three of the CBCT-Vet groups (depending on the degree 
of modification needed based on the initial group) will be conducted sequentially, such that information in 
the first group can be used to adapt the manualized intervention for the next group.
Psychoeducational healthy aging group: As part of this project, we will develop and test a 10-week 
psychoeducational group focused on topics in healthy aging to examine its feasibility as a control condition 
for a subsequent VA Merit-supported randomized controlled trial. Dr. Palmer, in addition to his VA position 
and roles, is an active member of the Center for Healthy Aging at UC San Diego. The Center for Healthy 
Aging has multiple resources for community education regarding healthy aging, including a library of 
videotaped community-focused talks, such as increasing happiness, mental resilience and health, nutrition, 
and physical activity. We will incorporate these videos as part of 90-minute sessions wherein the key 
information from talks is shown to participants, with a follow-up discussion and review period led by the 
group facilitator. In the context of the present feasibility study, we anticipate modifying and refining the 
content and format of the group in response to participant feedback.
Process and outcome measures: As a feasibility study, we will not be testing hypotheses regarding the 
efficacy of CBCT-Vet in reducing psychological distress with inferential statistics. However, in order to 
support our planned subsequent VA Merit application, we will be examining descriptive statistics of 
observed patterns and estimated effect sizes of change on key measures described below.
Baseline and post-intervention: Each participant will meet individually with a trained Research Assistant 
(RA; To Be Named (TBN)) for two 90-minute assessment sessions (baseline and post-intervention). The 
final assessment will be scheduled within 2-weeks of the participant’s final intervention group session. 
Measures will include:
Psychological distress: Brief Symptom Inventory-18 (BSI; depression, anxiety, and somatization) (Boulet 
.
& Boss, 1991)
Compassion, empathy, mindfulness, and social connectedness: As a feasibility study, we will use a larger 
array of measures than we anticipate employing in a subsequent VA Merit-supported RCT. Although we 
have prior experience with each of these measures in other contexts, their use in this feasibility study will 
enable us to more comprehensively identify those with most potential and which are most appropriate for 
this population. Measures will include: Self-
, Toronto Empathy 
Compassion Scale – Short Form
Questionnaire, Cognitive and Affective Mindfulness Scale – Revised, Social Connectedness Scale - Revised 
and the UCLA Loneliness Scale - Third Edition.
Well-being/Quality of Life: Physical and mental composite scores from the 12-item Short Form Health 
Survey (SF-12)  and 
.
Satisfaction with Life Scale
General positive psychological factors: 10-item version of the Connor-Davidson Resilience Scale , Life 
Orientation Test – Revised (a measure of optimism) , San Diego Wisdom Scale (SD-WISE) ) and Center for 
Epidemiological Studies – Depression Scale (CES-D; happiness factor).
Biomarkers: At the baseline and final visits, approximately 15 mL (2-3 teaspoons) of blood will be drawn 
from each participant by the VA Clinical Laboratory via standard blood draw. Three inflammatory markers 
will be assayed: high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis 
factor-alpha (TNF- ). Assays will be conducted using standardized methods through the VASDHS 6th floor 
research laboratory of Co-I Richard Hauger, MD.
Additional final visit measures: Participants will complete the modified Differential Emotions Scale (mDES) 
 at each weekly session to assess changes in positive emotion during the course 
(Fredrickson et al., 2003)

of treatment. Credibility of the interventions will be assessed at the final visit with a 3-item measure 
adapted from Borkovec & Nau (1972) and the Client Satisfaction Questionnaire (Attkisson & Greenfield, 
1994) as well as via post-intervention interviews.
Analytic plan:
Descriptive statistics will be used to summarize the variables as well as to detect outliers and data entry 
errors. When applicable, normality of the distribution will be examined for outcome variables and residuals 
of regression model with a normal probability plot. The present project is intended as a feasibility study 
that will inform, support, and guide development of a subsequent larger-scale VA Merit Award project. 
Therefore, the primary analysis will be descriptive rather than hypothesis testing. Since the interventions 
are delivered by group (8-10 participants per group), it is possible that measured or unmeasured 
characteristics of the participants in a given group or their interactions may affect psychological response 
to the intervention, attendance, and study outcomes. The analysis plan described below is based on no 
cluster effect of class. But we will assess the impact of clustering effects by fitting a random effects model 
for each outcome, and, if necessary, a random class effect will be included in the model to account for the 
correlations between the individuals in the same class. The intraclass correlation coefficient (ICC) will also 
be estimated to understand the correlation within class and provide advice for sample size adjustment in 
future studies.
 
Will older Veterans with psychological distress [anxiety and/or depression] enroll in and complete the 
proposed CM intervention? What is the completion rate? Do participants adhere to the treatment (complete 
practice at home)? We will assess the following outcome measures for enrollment, completion, and 
adherence to treatment:
1) 
 defined as the proportion of consented subjects among all screened and eligible 
Enrollment rate
patients;
2) 
 defined as the proportion of subjects who initiate the intervention among all consented 
Initiation rate
subjects;
3) 
defined as the proportion of subjects who complete 6 or more sessions (out of a total 
 
Completion rate
of 10 sessions) of intervention among those who start the intervention;
4) 
defined as average minutes that subjects practice at home each week. The mean 
 
Practice time at home
(and SD) or percentage will be calculated and the 95% confidence intervals will be estimated for all 
outcomes.
The associations between patient characteristics and other clinically important baseline variables with the 
enrollment, completion and adherence will be assessed using univariate tests (Wilcoxon rank sum test, 
Kruskal-Wallis test, Fisher’s exact test, or Spearman correlation coefficient).
 
Does CM show promise for improving well-being, symptom severity, and/or positive psychological factors 
relevant to successful aging? We will evaluate the improvement in depression and anxiety (BSI), social 
connection (SCS-R), satisfaction with life (SWLS) and positive emotions (mDES) from baseline to post-
intervention using a linear random effect model and time will be included as a main effect in the model. 
The random effects model is suitable for examining changes in outcomes in longitudinal studies. It will 
include all available data, minimizing the effects of missing data on the analyses.
We will also examine the mean (and SD) change scores for each inflammatory biomarker (hs-CRP, IL-6, 
and TNF- ), as well as the association of these changes with practice time.
Sample size assessment:
The sample size was determined based on practical consideration. Since this is a feasibility study, the goal 
is to examine the effect size such that it can guide future studies. We plan to enroll a total of 
approximately 24 to 30 participants for the CM groups (3 groups, 8-10 per group) as well as 10 
participants for the healthy aging group. Sample size analyses were focused on the CM group, and 
performed using statistical package R.
A two-sided type I error of 0.05 was assumed.
 The sample size justification was conducted for assessing the enrollment and completion rates (primary 
outcomes). We assessed the precision of estimates based on projected sample size. From previous 
investigations, the estimated enrollment and completion rates are between 0.57 and 0.82. Therefore, we 
considered a range of rate from 0.60 to 0.90 and estimated the margin of error (half of the width) for the 
95% confidence interval of enrollment and completion rates  The margin of error of a 95% confidence 
interval for a proportion is 1.96*p*(1-p)/(Square-root of ) where 
is the estimated sample and p is the 
n
n 
estimated rate. If an estimated intervention initiation rate is 0.80, a sample size of 30, 27 and 24 will 
produce a two-sided 95% confidence interval with a margin of error of 0.058, 0.071 and 0.064, 
respectively. For an estimated completion rate of 0.60, a sample size of 30, 27 and 24 will produce a two-
sided 95% confidence interval with a margin of error of 0.086, 0.091 and 0.096, respectively.
 We assessed the power for detecting a significant change in psychological outcomes. With a sample size 
of 24, 27 and 30, we will have 80% power to detect an effect size of 0.53, 0.56 and 0.60 for the change in 
outcomes from baseline to post-intervention. These effect sizes are achievable based on previous studies, 
where we observed an effect size of 0.5 for PHQ-9 (mean = 2.3, SD = 4.6), 0.65 for SCS-R (mean = 6.4, 
SD = 9.9), 1.4 for SWLS (mean = 9.0, SD = 6.6), 0.53 for mDES positive emotion (mean = 4.8, SD = 
9.1), and 5.35 for mDES negative emotions (mean = 7.5, SD = 1.4).

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Women and ethnic minorities: Women and ethnic minorities will be included in proportion to their 
representation of Veterans in the VASDHS and PCMHI program. This proportional sampling plan fosters 
both feasibility of the study and overall generalizability of findings. We recognize that the issues of anxiety 
and depression among women Veterans is exceptionally important, but warrants separate studies designed 
and focused specifically to address the issues of most salience to women Veterans.
Children: No children will be included as the scientific focus of this project is on older Veterans
 
Temporary COVID-19 Updates*
*Virtual Research Sessions and Cisco WebEx: During the COVID-19 administrative hold, ORD-funded 
grants are not permitted to have in-person study visits (including blood draw) for non-clinically critical 
research assessments. Therefore, we will conduct Compassion Meditation (CM) group therapy sessions and 
individual pre- and post-intervention sessions using the VA-approved telehealth technology, "Cisco 
WebEx." We will use Cisco WebEx to conduct the remaining CM group therapy sessions and post-
intervention sessions with the first participant cohort as well as to conduct virtual research sessions with 
future cohorts that are enrolled during the COVID-19 administrative hold. We will use Cisco WebEx to 
create digital recordings of the group therapy sessions for training and supervision of the study therapist. 
The recordings will be stored as digital files on the secure VASDHS R-drive network in the PI's R Drive 
folder (R: Palmer B) and will only be accessible to VA IRB-approved study staff. The use of Cisco WebEx to 
conduct virtual research visits is explained to participants in the new Verbal ICF/Script (see attached 
"Uploaded Documents").
Cisco WebEx is a subscription-based managed service that connects VA to a fully featured FedRAMP 
Cloud solution. It offers resources for conferencing, webinars, training, collaboration and more. VA staff 
can schedule and host conferences with both internal VA users and external participants. It is a PIV-
enabled and integrates Single Sign-On (SSO). Only staff that need to host or scheduled a meeting need 
an account.
All scheduled WebEx meeting links will be emailed to each participant securely via Azure encrypted email 
one day prior to the scheduled meeting day.
Additional information about Cisco WebEx privacy and security features is included in Sections 9.11 and 
27.5.
Prior to the first virtual group session, a member of the study team will assist each participant in using 
Cisco WebEx to ensure participants are comfortable using the program during the virtual research visits. 
The study therapist, Dr. Malaktaris, will also review proper participant etiquette and expectations for the 
new virtual format. Dr. Malaktaris will review the previous 3 therapy sessions materials and ensure the 
participants are comfortable moving forward in the remaining virtual therapy sessions. During the virtual 
group sessions, a member of the study team will be available to assist participants with any difficulties 
they may have.
We will also mail a packet to each participant, which will include information and instructions for virtual 
research visits, instructions for using Cisco WebEx, and printouts of the weekly study questionnaires. 
Participants will be instructed NOT write their name, date, initials, or any other personally identifiable 
information on any of these documents. Prior to each of the group training sessions, a member of our 
study team will meet one-on-one with each participant via Cisco WebEx to review and collect participants’ 
responses to the questionnaires.
*Blood-Based Inflammatory Biomarkers: The collection of blood-based inflammatory biomarkers, 
which were included for exploratory purposes, will not be collected during the COVID-19 administrative 
hold.
*New “Uploaded Documents” for use during COVID-19 Administrative Hold:
Verbal ICF/Script for virtual study sessions with the current participant group
General instruction letter for virtual research visits
“Joining a WebEx Meeting” instruction letter
“Participating in a WebEx Meeting” instruction letter
CAIR Pandemic Questionnaire**
4-item Duke Social Support Index**
6-item De Jong Gierveld Loneliness Scale**
**The CAIR Pandemic Questionnaire was developed by the VA Center of Excellence for Stress and 
Mental Health (CESAMH). The nature of our study population (ages 55 years and above, identified 
in VA primary care) includes risk factors for worse reactions to infection from this virus. In 
addition to the profound medical challenges inherent to the COVID-19 pandemic, the necessary 
safety and prevention social distancing requirements are likely to affect social interactions, 
relationships, and loneliness. Some aspects of these changes may be positive for some persons,