Mindfulness-Based Cognitive Therapy Delivered Via Group Videoconferencing for Acute Coronary Syndrome Patients With Depressive Symptoms: A Pilot RCT
Phase: NA
Conditions: Cardiovascular Diseases, Acute Coronary Syndrome, Depression
Sponsor: Massachusetts General Hospital

 
MBCT Via Group Videoconferencing for Acute Coronary Syndrome Patients With Depressive 
Symptoms: A Pilot RCT 
 
NCT04799899 
 
Today’s Date: 10/17/2023 
Document Version Date: 12/07/2021 
 
 

PARTNERS HUMAN RESEARCH COMMITTEE 
DETAILED PROTOCOL 
 
Version Date: 12/07/2021 
I. 
BACKGROUND AND SIGNIFICANCE 
a. Historical Background 
 
It is critical to treat depression in patients with acute coronary syndrome 
(ACS). Among the one million ACS patients in the U.S. each year (e.g., 
myocardial infarction, unstable angina), up to 45% have elevated depression 
symptoms. Even mild elevations in depression symptoms double the risk of 
mortality after ACS. Meta-analyses of over 4,000 ACS patients and 53 studies 
have found that depression is an independent risk factor for recurrent cardiac 
events, re-hospitalizations, cardiac mortality, and all-cause mortality, beyond 
other traditional risk factors. Left untreated, depression persists for years and 
doubles the risk of death through biological and behavioral mechanisms. 
Biologically, depression causes inflammation through neuroendocrine alterations, 
leading to atherosclerotic plaque formation and rupture. Behaviorally, ACS 
patients need to make multiple lifestyle changes, but depression symptoms (e.g., 
disinterest, lack of motivation) prevent engagement in cardiac health behaviors 
(e.g., physical activity, diet). Thus, depression treatment is necessary to promote 
biological and behavioral changes important for survival.  
Depression treatments for ACS patients need improvement. More ACS 
patients prefer psychological (75%) rather than pharmacological depression 
treatments (20%). However, the recommended psychological intervention, 
cognitive-behavioral therapy (CBT), has limited effects on depression and cardiac 
outcomes. Targeting the mechanisms that link depression to ACS could improve 
treatment efficacy, but CBT does not aim to target a key mechanism, i.e., 
inflammation. Consistent evidence from multiple meta-analyses suggests that 
depression is associated with elevated levels of inflammatory cytokines, 
particularly C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-α. These 
same specific cytokines are also elevated, positively correlated with depression 
symptoms, and independently increase the risk of mortality in patients with 
cardiac disease. Of note for depression treatment, the relationships are 
bidirectional: treating depression reduces inflammation, but reducing 
inflammation also reduces depression symptoms, making CRP, IL-6, and TNF-α 
salient treatment targets for both depression and cardiac health in ACS patients. 
Mindfulness-Based Cognitive Therapy (MBCT) could improve depression 
and cardiac health for ACS patients. MBCT is an 8-week manualized group 
intervention that combines CBT with mindfulness meditation to treat depression; 
it is as effective as antidepressant medication for relapse prevention and reduces 
symptoms in active depression. The American Heart Association (AHA) recently 
highlighted the potential benefits of meditation for cardiac health and the need for 

further research in this area. Indeed, through the addition of mindfulness training, 
MBCT could improve both depression and cardiac health. First, mindfulness 
meditation can reduce levels of CRP, IL-6, and TNF-α, which reduces depression 
symptoms and benefits cardiac health. Second, meditation increases pro-sociality 
(e.g., compassion, altruism) and social support, both of which reduce depression 
symptoms. Given that social isolation is an independent risk factor for ACS 
mortality and pro-sociality improves cardiovascular functioning, social 
improvements could have direct benefits on cardiac health. Next, MBCT 
improves emotion regulation (e.g., rumination about a recurrent event, acceptance 
of lifestyle changes), which is a key treatment target for depression. Lastly, 
mindfulness training improves cardiac health behaviors, likely by improving 
emotional outcomes. Improvements in depression also lead to further 
improvements in inflammation and pro-sociality to further promote cardiac 
health. 
 
b. Previous pre-clinical or clinical studies leading up to and supporting the 
proposed research 
 
Research supports the feasibility of MBCT for depression treatment in ACS 
patients. Two meta-analyses (18 trials) have demonstrated that mindfulness 
interventions are feasible, acceptable, and reduce depression symptoms in patients 
with cardiovascular disease (d = .35 - .61). ACS patients are similar to other 
cardiac disease patients (e.g., age, comorbidities) and thus are also likely to find 
mindfulness interventions acceptable. In fact, ACS patients may be most 
interested in depression treatment because they are motivated to improve their 
health following the acute cardiac event. Most research in patients with 
cardiovascular disease has used Mindfulness-Based Stress Reduction (MBSR), 
which is very similar to MBCT, but does not incorporate a CBT approach to 
target depression specifically. MBCT shows larger effect sizes for depression than 
MBSR and thus might be particularly useful for ACS depression treatment.  
An electronic health (e-health) approach is needed to improve treatment 
outreach. Most ACS patients prefer behavioral depression treatments, but these 
are burdensome, not widely accessible, and present barriers. In a study of nearly 
700 primary care patients, 78% of those with depression reported logistical and 
emotional/physical barriers to accessing treatment. E-health technologies can 
overcome these barriers to reach more patients and effectively treat depression. In 
a study of over 200 patients with cardiovascular disease, 85% had internet access 
and 74% of them preferred e-health interventions. ACS patients tend to be older 
adults (>65 years), the fastest growing group of computer and internet users, who 
report positive experiences with technology used at home. A systematic review of 
54 trials found that e-health interventions are feasible for older adults with 
medical problems, including those with cardiovascular disease.  

It is feasible to deliver MBCT via e-health technologies. E-health mindfulness 
interventions are feasible and can improve health outcomes in patients with 
medical problems. However, research has focused on websites that patients use 
independently, which does not allow for synchronous contact with a clinician or 
peers, leading to a smaller treatment effect and increased attrition, and eliminating 
the health benefits of social support. Group videoconferencing combines 
accessibility with synchronous contact, shows comparable efficacy with in-person 
treatments, and is a validated approach to behavioral intervention delivery. Two 
studies demonstrated the feasibility of videoconferencing to deliver mindfulness 
interventions to patients at their own home. Thus, group videoconferencing is a 
promising but underutilized approach to MBCT delivery. 
MBCT via group videoconferencing is likely to be attractive and feasible for 
ACS patients. Web-based mindfulness interventions are feasible and reduce 
depression symptoms in patients with cardiovascular disease and other older adult 
populations. The AHA has emphasized that a benefit of meditation for cardiac 
health is the possibility of online delivery, but no research has applied MBCT via 
group videoconferencing to ACS patients with elevated depression symptoms.   
Our preliminary work supports the use of virtual MBCT for ACS patients.  
We recently conducted a qualitative study (individual patient interviews) to solicit 
patient’s perspectives and needs for a behavioral depression treatment based on 
MBCT (IRB Protocol Number 2018P001000). Patients were open and interested 
in a mindfulness program, identified a range of symptoms and needs for the 
intervention to target, offered suggestions for promoting videoconferencing 
feasibility, and expressed openness to participate in dried blood spot research 
procedures. We developed an adapted MBCT protocol based on this feedback, 
which we recently tested in an open pilot trial of n=7 patients with ACS and 
depressive symptoms (IRB Protocol Number 2020P000045). Those who 
completed the intervention (n=4) reported high ratings of intervention 
acceptability, videoconference acceptability, comfort with the dried blood spot 
procedures, and improvements in depression and anxiety symptoms. 
 
c. Rationale behind the proposed research and potential benefits to patients 
and/or society 
 
The rationale behind the proposed research is that the high comorbidity between 
depression and cardiovascular disease reflects a complex, mind-body interaction 
that must be treated using a comprehensive mind-body approach. Mindfulness-
based cognitive therapy is an evidence-based intervention with efficacy to treat 
depression, and improve quality of life in patients with cardiovascular disease. 
However, this is the first research to adapt MBCT specifically to the needs of 
patients with depression after an acute cardiac event, test the efficacy of this 
intervention an randomized trial with an active control group. The potential 

benefits to patients in the trial include peer support, attention from a trained 
clinician, and learning information and skills to improve mood, coping, cardiac 
health, and quality of life. Given that cardiovascular disease is the leading cause 
of death worldwide, and the substantial added burden of co-occurring depression 
and cardiovascular disease, the proposed research has the potential to identify a 
novel, efficacious, and scalable intervention to improve public health. 
 
II. 
SPECIFIC AIMS 
a. Aim 1: To establish, in a pilot RCT (approx. N=50 participants) with a time- and 
attention-matched health enhancement control, (a) the feasibility of the 
recruitment procedures (screening, eligibility, enrollment rates), and feasibility 
and acceptability of the (b) MBCT and control interventions (adherence, 
retention, fidelity, satisfaction, group videoconferencing delivery) and (c) data 
collection procedures by group (adherence, satisfaction). Hypothesis 1a: 
Recruitment will be feasible as evidenced by screening, eligibility, and enrollment 
rates; (1b) the MBCT and control interventions and (1c) data collection 
procedures in both groups will be feasible and acceptable. 
 
b. Aim 2 (exploratory): To explore within-group changes in psychosocial and 
physical health outcomes following virtual MBCT and the control intervention 
(e.g., depression, inflammation, emotion regulation, pro-sociality, and health 
behaviors).  
 
III. 
SUBJECT SELECTION 
a. Inclusion/exclusion criteria 
 
Inclusion criteria: 
1. Lifetime ACS per medical record and/or patient confirmation 
2. Current elevated depression symptoms (PHQ-9>5) 
3. Age 35-85 years 
4. Access to high-speed internet  
5. Massachusetts General Brigham patient 
 
Exclusion criteria: 
1. Active suicidal ideation or past-year psychiatric hospitalization (per patient 
report and/or medical record review) 
2. Non-English-speaking 
3. Cognitive impairments preventing informed consent per medical record review 
and/or cognitive Screen < 4 
4. Patient deemed unable to complete the study protocol or has a condition that 
would likely interfere with the study 
5. Is not a Massachusetts General Brigham patient 
 
 

b. Source of subjects and recruitment methods 
 
Study staff will engage in multiple recruitment modalities to obtain a diverse 
sample of study participants.  
First, patients will be recruited through the RPDR. We will include patients who 
have and have not agreed to participate in RODY (Research Options Direct to 
You).  
“RODY No” patients identified from the RPDR will be sent a combined 
opt-out letter from a member of their healthcare team (e.g., cardiologist, primary 
care provider, nurse practitioner, etc.) and the study team. This letter will be sent 
via paper mail or Patient Gateway. This letter will describe the study procedures 
and ask patients to contact the study team within 2 weeks if they would not like to 
be contacted to hear more about the study. Patients will have the option to opt-out 
via phone or email. Those who do not opt-out will be contacted via phone by the 
PI or a trained and CITI-certified research staff member. Patients will be read a 
brief phone script (attached) informing them of the purpose of the call and asking 
if they would like to hear more about the research study. Those who agree will 
undergo eligibility screening (attached). Those who are eligible and interested 
will undergo informed consent, described below. 
“RODY Yes” patients will receive an opt-out letter from the study team 
(attached). All other recruitment procedures will be the same as for “RODY No”.  
Only the Principal Investigator and trained research staff will identify and 
contact patients. Up to approximately 3 calls will be made to a given patient before 
assuming the patient is not interested and no longer attempting to contact them. 
Second, patients will be recruited through hospital flyers (e.g., inpatient/outpatient 
cardiology clinics, psychiatry clinics). Advertisements will ask patients to contact 
study staff if they are interested in learning more about the study. In situations 
where a briefer ad is more feasible (e.g. virtual postings on iPads and computer 
screens in clinic waiting rooms), a shortened version of the flyer will be posted. 
The flyers are included in the IRB submission. Specific phone numbers on the 
flyers will be filled in based on the contact information for the current RA. Phone 
screening and consenting procedures will be the same as described above. 
Third, patients will be recruited via direct referrals from their providers (e.g., 
cardiologists, psychiatrists). We will inform providers about the study (e.g., via 
short presentations at their team meetings) and provide them with flyers. 
Providers may either obtain verbal permission from the patient to share their name 
and contact information with study staff, or they may provide patients with the 
flyer to contact study staff on their own. The outreach and phone screening 
procedures will be the same as described above.  
 

Fourth, patients will be recruited from inpatient cardiac units within MGH. Study 
staff will review inpatient censuses from MGH cardiac units and/or participate 
with invitation in inpatient cardiology rounds to identify patients whose available 
admission information (e.g., laboratory studies) suggests ACS. Study staff will 
ask the clinical team to confirm the cardiac diagnosis and inquire with the patient 
whether the patient is willing to hear about an optional study. For willing patients, 
study staff will discuss the study with the patient and assess for additional study 
criteria using the same screening procedures described above (e.g., PHQ-9 
administration). For patients who screen out or decline assessments, we will retain 
no personal information. Patients who are interested in hearing about the study 
and completing the screener, but do not want to do so during their hospitalization, 
will be given the option to be contacted by phone after their discharge. The same 
screening procedures would be done by phone at that time.   
Fifth, research staff will use EPIC to assist in recruitment. To this end, we have 
worked with the Partners eCare Research Core (PeRC) to set up the necessary 
steps. PeRC leverages the Epic EHR to assist researchers in identifying and 
recruiting patients for their research studies conducted at Partners HealthCare. 
PeRC will put together a report through EPIC based on a list of predetermined 
variables (please see attached list of variables to be extracted). After Epic training, 
and hands-on guidance from the PeRC team, study staff will run this automated 
report within Epic to identify potentially eligible ACS patients. Study staff will 
review patients’ charts to confirm potential eligibility as needed (e.g., confirm 
admission diagnoses). Study staff will send patients the same opt-out letters 
described above via paper mail or Patient Gateway according to RODY status, 
and the outreach and screening procedures will be the same.  
In addition, the PI or trained RA will view Epic patient lists for cardiac units (e.g., 
Ellison 10, Ellison 11) to identify patients admitted for ACS. Patients’ charts will 
be reviewed to determine if they are RODY or non-RODY patients. RODY 
patients will receive a phone call or opt-out letter inviting them to participate in 
the study. For non-RODY patients, study staff will obtain permission from a 
member of the patient’s healthcare team to send a combined opt-out letter from 
the provider and study team.  
Sixth, patients will be recruited through the study’s MGB Rally page. Research 
staff will publish an informational Rally page to advertise the study to MGB 
patients. Patients will be able to contact study staff if they are interested in 
learning more about the study. Specific phone numbers on the Rally page will be 
filled in based on the contact information for the current RA. Phone screening and 
consenting procedures will be the same as described above. 
 
IV. 
SUBJECT ENROLLMENT 

a. Methods of enrollment, including procedures for patient registration and or 
randomization 
 
Study staff will approach patients about participating in the study using one the 
modalities discussed in section III.b. For patients who are not interested in 
participation, study staff will discontinue contact. For patients who are interested 
in participation, study staff will screen patients for eligibility (criteria detailed in 
section III.a). If a patient screens as eligible, they will be asked to provide 
informed consent using one of the procedures detailed in section IV.b. Following 
informed consent patients will be 1:1 randomized (see section IV.c) and enrolled 
in the study using a random number generator.  
 
b. Procedures for obtaining informed consent 
 
A member of the study staff will determine patients’ eligibility status, explain the 
purpose of the study and study procedures, and answer any questions prior to 
completing informed consent per the information below.  
 
Patients will be provided with the informed consent document electronically or 
via paper mail. The informed consent document will be carefully reviewed with 
study staff via discussion with the patient either by phone or videoconference. 
Patients who are recruited while inpatient may also have the option to complete 
consent in person. The consent form will include a description of all study 
procedures and information about potential risks and benefits of participation. It 
will state that participation is voluntary, that participants can refuse to answer 
questions that make them uncomfortable, that participants can discontinue 
participation at any time, and that not completing the study will not compromise 
their medical care. Special attention will be given during the consent process to 
the implications of the study design (e.g., randomization) and of receiving an 
intervention or educational information online via videoconferencing services. 
Subjects will be explicitly informed that videoconferencing services provide 
secure HIPAA-compliant videoconferencing software. We will explain to 
participants that although we will do our best to ensure confidentiality on our end, 
there is still a potential risk of loss of confidentiality. Participants will also be 
advised to wear headphones and sit in a quiet place to protect their own, and other 
group members’ privacy.  
After the form is reviewed and all of the patient’s questions have been answered, 
the patient may then sign and submit the form electronically or via paper mail. All 
patients will be provided with study staff contact information if any questions or 
concerns regarding the research arise.  
As stated above, member of the study staff will obtain informed consent in one of 
three ways, depending on patient preference: 1) electronically (via REDCap or 
emailed pdf of the consent form), 2) via paper mail correspondence, or 3) in 

person (for patients who are recruited while inpatient). Participants who opt to 
receive the consent materials via paper mail will be asked to provide a mailing 
address. Participants who opt for electronic consent will be made aware of 
security concerns related to email communication (as described earlier) and, after 
specifying their preference for encrypted or unencrypted email, be emailed the 
informed consent portal via REDCap or electronic copy of the consent form.   
 
REDCap Electronic Informed Consent Process (EIC):  
Participants who choose to complete the consent form electronically will be 
emailed a link for the informed consent portal via REDCap. The REDCap link 
will connect the participant to an encrypted REDCap portal; the 
Electronic/Paperless Consent Template Project will be used. Once the participant 
confirms receipt of the EIC form link, they will be prompted to enter in their full 
name and birthday to access the informed consent form and verify their identify. 
This portal will have the electronic (paperless) consent form, exactly identical in 
content to the paper version, to guide the participant through the consent 
discussion with study staff over the phone. The participant will be given ample 
opportunity to ask questions and take their time to consider their participation. If a 
participant would prefer, they may return to the EIC portal as many times as they 
would like to review the consent form on their own time. When ready to sign 
consent, participants will digitally sign and date/time the consent form. 
Additionally, the participant will be prompted after signing to indicate the method 
through which they would like to receive a copy of the consent form for their 
record: digitally or through hard copy. If a participant would like to receive a 
copy of the consent form digitally, they will be asked their preference to receive 
the email as encrypted, the default, or opt-out and receive the email unencrypted. 
These options allow participants to be informed of what an encrypted (Send 
Secure) email would appear as in their inbox and the steps to get into the email, or 
alternatively, to give permission to receive the email without this extra layer of 
security but in a more accessible format. Partner’s Healthcare language 
concerning the Send Secure feature is included to assist in this decision. Study 
staff will confirm receipt of the digital signature and will sign and date the 
consent form as the consenting study staff member. At any point, if a participant 
would prefer to receive a hard copy of the consent form, the EIC process will 
stop, and study staff will commence the phone and mail correspondence process 
for informed consent. 
 
Paper Mail Correspondence  
Participants may also elect to receive an electronic copy (pdf) of the consent form 
via email, according to the email security procedures previously described. In this 
case the participant could print and sign the form and either scan/email or send via 
paper mail back to the research team.   

If the participant would prefer to complete the informed consent process via paper 
mail, study staff will start by facilitating the informed consent discussion over the 
phone. Once all questions are answered to the satisfaction of the participant, study 
staff will mail 2 signed copies of the informed consent form for the participant to 
review, sign and mail back one copy at their convenience. Participants will be 
provided with a pre-stamped, pre-addressed envelope for their return. Study staff 
will maintain one copy of the informed consent form for study records, 
participants will be instructed to maintain one copy for personal reference.  
 
In-person Informed Consent Process 
Study staff will go through the informed consent discussion in a hospital or 
private room to protect patient confidentiality and answer any questions. Upon 
consent, study staff will maintain one copy of the informed consent form for study 
records, and participants will be instructed to maintain one copy for personal 
reference. Patients who would like more time to consider participation are able to 
take the forms home with them to review, and if interested, they may complete the 
consent process electronically or proceed to mail back the consent forms. 
 
Following consent, the participant will be asked to provide and clarify their 
preferred contact modalities for their participant throughout the study. They will 
be informed that they can change these preferences at any time. Study staff will 
document the outcome of this conversation and proceed with participant contact 
accordingly.  
 
c. Treatment assignment and randomization 
 
Participants will be randomized to a MBCT or a time- and attention-matched 
health enhancement control in a 1:1 design using a random number generator.  
 
V. 
STUDY PROCEDURES 
a. Study visits and parameters to be measured 
 
Adapted MBCT intervention 
The MBCT intervention is based on Mindfulness-Based Cognitive Therapy 
(MBCT), an evidence-based, manualized protocol for treating depression 
symptoms. We have developed an adapted MBCT protocol based on our 
preliminary qualitative work and open pilot trial and continue to make iterative 
refinements based on patient feedback. Participants randomized to the MBCT 
intervention will be expected to participate in 8-weekly virtual sessions, in 
conjunction with approximately 30 minutes of at-home daily practice. Each 
weekly virtual session will last approximately 1.5 hours. A licensed mental health 
provider (e.g., LICSW, PhD) trained in the MBCT protocol will deliver the 

intervention. The interventionist will receive ongoing supervision and feedback 
from the PI or MBCT mentor. The MBCT intervention will not be delivered 
clinically; it is a psycho-educational intervention. We will also send audio 
recordings used for home mindfulness practice via Partners email (send secure or 
unencrypted if the patient prefers). 
 
Health Enhancement Control Group 
The control intervention will be a group videoconferencing program focused on 
depression and cardiac health education (e.g., relationship between depression and 
cardiac health, cardiac risk factors, cardiac health behaviors, finding resources for 
mental health care). It will follow the same structure as MBCT but will not 
contain mindfulness practices or psychoeducation. Participants randomized to the 
health enhancement control group will be expected to participate in 8-weekly 
virtual sessions, where each session will last approximately 1.5 hours. To promote 
equivalent between-session practice, participants will identify health behavior 
goals to work on and track over the week. A licensed clinician or pre-doctoral or 
post-doctoral fellow with supervision from a licensed clinician will lead the 
control group. 
 
Data collection 
For both the intervention group and control group study assessments include a 
battery of self-report surveys administered at baseline, post-intervention, and 3-
month follow-up; session satisfaction surveys administered after each intervention 
session; post-intervention individual exit interviews (conducted via telephone or 
videoconference); blood spot samples self-collected by participants at baseline, 
post-intervention, and 3-month follow-up (submitted to the research team via 
paper mail). The intervention group will complete home practice logs submitted 
between each intervention session. Surveys and home practice logs may be 
completed via REDCap, email, paper mail, phone, or videoconferencing 
depending on patients’ preferences. Data collection will also consist of viewing 
and extracting data from the EHR to assess medical and demographic variables 
(e.g. medical diagnoses, medications, cardiac rehab attendance) and/or confirm 
eligibility. REDCap is a secure online data collection system.  
 
Survey measures 
The self-report survey measures will be the same for the MBCT and control 
groups. The surveys will be administered within approximately 1-2 weeks before 
and after the intervention and at 3 months post-intervention. This battery will 
include the following validated self-report surveys: Assessment of Survivor 
Concerns (fear of recurrence), CAMS-R (mindfulness), Cardiac History and 
Symptoms, Current Experiences Scale (CES; resiliency), COVID items, 

demographic questionnaire, Expectancy Questionnaire, Experiences 
Questionnaire (decentering), Group cohesion scale, Hospital Anxiety and 
Depression Scale (HADS; depression and anxiety), Interpersonal Reactivity Index 
(IRI; empathy), MAIA-2 body subscales (interoception), MBCT-AS Checklist 
(fidelity checklist), PHQ-9 (depression), Medical Outcomes Study – Specific 
Adherence Scale (MOS-SAS; health behaviors), one item from the Short Form-12 
(SF-12), Self-Other Four Immeasurables (SOFI; self and other compassion), 
PROMIS Physical Function (PROMIS-PF; physical function), and The Positive 
and Negative Affect Schedule-Positive Affect (PANAS-PA). The post-
intervention survey will also include a group cohesiveness measures to assess 
perceived connection with other group members as well as intervention 
satisfaction questions to assess acceptability. The 3-month follow-up survey will 
include questions about continued mindfulness practice. The baseline survey, 
post-intervention survey and post-intervention survey will all include questions 
related to COVID-19. All three survey batteries are included in the IRB 
submission. 
Post-session surveys 
Both intervention and control group participants will receive post-session surveys. 
The post-session surveys will be administered immediately after each of the 8-
sessions and will assess participants’ perceptions, and likes and dislikes, of 
specific intervention or control group components. The post-session surveys for 
both the control and intervention group are included in the IRB submission. 
Home practice logs 
Only the intervention group will receive weekly home practice logs. Prior to each 
session participants will be asked to email, mail, or complete via REDCap a 
record of their at-home mindfulness practice since the previous session. The home 
practice logs are included in the IRB submission. 
Exit interview 
Upon completion of the intervention, participants from both the intervention and 
control group will be asked to complete a 30-60-minute exit interview via phone 
or videoconference. These interviews will be audio- and/or video-recorded for 
transcription.  
Dried blood spots 
Both intervention and control group participants will be asked to provide dried 
blood spot samples. Within one week before and after the intervention and 3-
months-post intervention, participants will be asked to provide self-collected 
whole dried blood spots to assess IL-6, CRP,  and TNF-α.  
 

b. Drugs to be used 
There will be no drugs used in this study. 
 
c. Devices to be used 
There will be no devices used in this study.  
 
d. Procedures/surgical interventions 
 
At baseline, post-intervention, and 3 months following the end of the intervention, 
participants will be asked to complete a dried blood spot sample collection using a 
minimally invasive finger skin prick technique, which involves pricking the finger 
with a lancet, milking the finger to produce 5-10 drops of blood onto filter paper, 
allowing the blood spots to dry, and mailing it to the study team at MGH in a 
secure envelope. Prior to the start of the intervention, an RA will guide the 
participant in self-collecting blood samples via a videoconference call or phone 
call (per the participant’s preference). Participants will also be sent written 
instructional handouts. The RA will ask the participant a series of questions to 
gauge understanding, provide corrective feedback, and answer any questions the 
participant might have before proceeding to guide the participant in the procedure.  
Participants will be asked to allow the sample to dry overnight, document the date 
the sample was taken on the filter paper, and mail it to the study team at MGH the 
next morning. Samples will be received by the RA, who will mark the date of 
receipt in the study database. Samples can be in ambient air for up to 2 weeks 
without degradation. We will ask participants to mail the samples within 24 hours 
of taking them to minimize the time samples are in ambient air. If samples are 
received beyond 2 weeks of the date indicated on the filter paper, we will ask 
participants to provide another sample, and participants will be made aware of 
this possibility in the consent form. Once received, the RA will bring the samples 
to be stored in a -20°C freezer in the MGH Clinical Research Center lab or mail 
them to our collaborator at the Laboratory for Human Biology Research at 
Northwestern University for storage and processing. Blood spots can be frozen at 
this temperature for several years without degradation.  
When initially mailing the blood spot kit to participants, the RA will indicate the 
participant’s study ID number, group assignment, date, and data collection 
timepoint on the filter paper. Participants will be informed not to write any 
personally identifying information on the filter paper. This will keep the blood 
samples de-identified.  
Collecting whole blood spots with filter paper has been used in hospitals for 
decades to collect blood from newborns, and it has proven to be a safe and 
effective means for collecting and transporting samples in several large NIH-
funded field-based studies. The Centers for Disease Control and Prevention have 
maintained independent quality control efforts and have reported that these 

approaches can achieve the same level precision and reproducibility of standard 
blood collection methods. Our collaborators at Northwestern University have 
pioneered this technique as leaders in the development, validation and application 
of whole dried blood spots as a convenient means for collecting, transporting, and 
processing blood samples from community settings and mind-body intervention 
research including clinical trials. We used these methods in our recent open pilot 
trial and found promising feasibility and acceptability in this population (IRB 
Protocol Number 2020P000045). The dried blood spot samples will be collected 
using a commercially available, FDA approved Whatman™ 903 Proteinsaver 
cards and BD Microtainer® Contact-Activated Lancets (gauge 14, incision depth 
2mm (8/10”). The samples will not undergo CLIA tests and will be stored for 
approximately 1-2 years. 
 
There will be no surgical interventions for this study.  
 
e. Data to be collected and when the data is to be collected 
 
The self-report survey measures will be the same for the MBCT and control 
groups. The surveys will be administered within approximately 1-2 weeks before 
and after the intervention and at 3 months post-intervention. This battery will 
include the following validated self-report surveys: Assessment of Survivor 
Concerns (fear of recurrence), CAMS-R (mindfulness), Cardiac History and 
Symptoms, Current Experiences Scale (CES; resiliency), COVID items, 
demographic questionnaire, Expectancy Questionnaire, Experiences 
Questionnaire (decentering), Group cohesion scale, Hospital Anxiety and 
Depression Scale (HADS; depression and anxiety), Interpersonal Reactivity Index 
(IRI; empathy), MAIA-2 body subscales (interoception), MBCT-AS Checklist 
(fidelity checklist), PHQ-9 (depression), Medical Outcomes Study – Specific 
Adherence Scale (MOS-SAS; health behaviors), one item from the Short Form-12 
(SF-12), Self-Other Four Immeasurables (SOFI; self and other compassion), 
PROMIS Physical Function (PROMIS-PF; physical function), and The Positive 
and Negative Affect Schedule-Positive Affect (PANAS-PA). The post-
intervention survey will also include a group cohesiveness measures to assess 
perceived connection with other group members as well as intervention 
satisfaction questions to assess acceptability. The 3-month follow-up survey will 
include questions about continued mindfulness practice. The baseline survey, 
post-intervention survey and post-intervention survey will all include questions 
related to COVID-19. All three survey batteries are included in the IRB 
submission. 
At the end of each session all participations will complete a post-session survey 
assessing session likes and dislikes. Between each session intervention 
participants will be asked to complete home practice logs documenting the 
frequency of and the thoughts related to their weekly mindfulness practice.  
 

Upon completion of the intervention, participants from both the intervention and 
control group will be asked to complete a 30-60-minute exit interview via phone 
or videoconference. 
 
Both intervention and control group participants will be asked to provide dried 
blood spot samples within one week before and after the intervention and 3-
months-post intervention. Samples will be used to examine IL-6, CRP,  and TNF-
α levels.  
 
Data collection will also consist of viewing and extracting data from the EHR to 
assess medical and demographic variables (e.g. medical diagnoses, medications, 
cardiac rehab attendance) and/or confirm eligibility. REDCap is a secure online 
data collection system. 
 
Figure 1. Overview of pilot RCT data collection procedures  
 
 
VI. 
BIOSTATISTICAL ANALYSIS 
a. Specific data variables being collected for the study 
 
The primary outcomes are feasibility and acceptability of the intervention and research 
procedures (Table 1). Study staff will record all feasibility outcomes throughout recruitment, 
screening, enrollment, and the intervention, data collection, and follow-up phases. 
Table 1. PRIMARY OUTCOMES 
Feasibility 
Recruitment 
>70% consent to screening; >70% meet screening criteria; >70% of eligible enroll; enroll >20 
participants/month 
Eligibility criteria 
< 20% ineligible due to each criterion; reasons for ineligibility; reasons for refusal; characteristics of 
refusers 
MBCT and control 
interventions 
Adherence: >75% session attendance; retention: >75% post-assessments, >70% follow-up 
assessments completed; fidelity: checklist score >80%; >75% complete home practice at least 3 
days/week 
Videoconferencing 
<20% of connections dropped during session; <20% of sessions missed due to technical problems; 
number (M<2.0) and type of problems; <20% ask for extra training, type of extra training needed 
Blood spots 
Adherence: >75% submitted at baseline, post-intervention, >60% submitted at follow-up; 80% 
adequate quality  
Acceptability 
MBCT and control 
interventions 
Session satisfaction and helpfulness, enjoyment, relevance, utility of each session component 
(1=not at all, 10=very much; M>7.5; post-session survey); overall program satisfaction (M>7.5), 
>75% plan to use the skills, >75% would recommend the program to others (post-intervention 

 
The exploratory outcomes are within-group changes in health-related variables, measured at 
baseline, post-intervention, and 3-month follow-up. All self-report measures are validated (Table 
2). 
 
 
b. Study endpoints 
The primary study endpoint is feasibility and acceptability of the intervention at the end 
of the trial (6 months post-baseline; see Table 1 for more information).  
 
c. Statistical methods 
 
Aim 1. I will calculate frequencies and proportions to assess feasibility outcomes, 
and means and standard deviations or medians and interquartile ranges to assess 
acceptability ratings. T-tests or chi-square tests will be used to compare eligible 
patients who did and did not enroll in terms of demographic and clinical variables, 
and feasibility and acceptability across enrolled patients based on gender, and 
medical/psychiatric factors. I will use independent samples t-tests to compare 
adherent and non-adherent participants from each group on baseline depression and 
clinical and demographic variables. Exit interviews will be audio recorded, 
transcribed, and iteratively analyzed using thematic content analysis. 
Approximately 2-3 members of the study team will review the transcripts to 
identify common themes and develop a coding framework. We will review our 
results for agreement and comparison to the raw data, and resolve discrepancies 
survey); likes, dislikes, suggestions for improvement (exit interview); >60% continue meditation 
practice (follow-up survey)  
Videoconferencing 
Ease and confidence of use (1=not at all, 10=extremely M>7.5), interference of technical problems 
(1=none, 10=extreme; M<2.0), audiovisual quality and overall satisfaction (1=poor,10=excellent; 
M>7.5; post-session survey); pros and cons, suggestions for improvement (exit interview)  
Blood spots 
Ease of data collection and submission (1=not at all, 10=extremely; M>7.5), level of pain (1=none, 
10=extreme; M<2.0; post-intervention survey); concerns, suggestions for improvement (exit 
interview) 
Note. M = mean. Benchmarks are informed by my pilot data, prior literature and prior clinical trials.  
Table 2. EXPLORATORY OUTCOMES 
Variable 
Measurement 
Fear of Recurrence  
Assessment of Survivor Concerns  
Mindfulness  
CAMS-R   
Resiliency  
Current Experiences Scale (CES) 
Decentering 
Experiences Questionnaire  
Depression and Anxiety  
Hospital Anxiety and Depression Scale (HADS) 
Empathy 
Interpersonal Reactivity Index (IRI)  
Interoception 
MAIA-2 body subscales  
Fidelity checklist 
MBCT-AS Checklist  
Depression 
PHQ-9  
Health behaviors  
Medical Outcomes Study – Specific Adherence Scale (MOS-SAS) 
Everyday health 
One item from the Short Form-12 (SF-12) 
Social connectedness 
Self-Other Four Immeasurables (SOFI) 
Physical function 
PROMIS- Physical Function (PROMIS-PF) 
Positive Affect  
The Positive and Negative Affect Schedule-Positive Affect (PANAS-PA) 
IL6, TNF-α, CRP 
Whole dried blood spots 

through discussion with Dr. Park until. All transcripts will be coded according to 
the coding framework. 
Aim 2. Exploratory outcomes. As a pilot feasibility trial, I will explore within-
group changes in emotional, physiological, and health behavior variables from 
before to after the intervention. I will examine frequency distributions for all 
variables and use non-parametric tests if needed. I plan to use linear mixed effects 
models with repeated measures and an unstructured covariance matrix to assess 
changes within the MBCT and control group for the following dependent variables: 
depression symptoms, inflammation, emotion regulation, pro-sociality, health 
behaviors, and cardiac health (Table 2). The predictor variables will be time (fixed 
effect; two levels: baseline, post-intervention) and covariates relevant for each 
dependent variable (random effects; section 5.1). I will explore follow-up outcomes 
in separate models where time is a fixed effect (three levels: baseline, post-
intervention, follow-up) and covariates are included as random effects, with pair-
wise comparisons between follow-up and the other two time-points. I will explore 
correlations between changes (post-intervention minus baseline) in depression 
symptoms and inflammation, emotion regulation, pro-sociality, and health 
behaviors. For dropouts, I will impute missing data using maximum likelihood 
estimation and, as a sensitivity analysis, the last observation carried forward. For 
all analyses, trends will be considered based on a two-tailed α=.10. 
 
d. Power analysis 
In alignment with the advice of the funding institute (NCCIH) and intended 
purpose of pilot feasibility trials, we did not conduct a power analysis for this 
trial. Rather, we selected a sample size (N=40) based on pragmatics, the needs of 
the trial, and our team’s previous pilot studies, that will provide an accurate 
indication of the feasibility of the research procedures. 
 
VII. 
RISKS AND DISCOMFORTS 
a. Complications of surgical and non-surgical procedures 
There are no surgical procedures as part of this study. Given that participants do 
not need to physically come to the hospital to participate in any study procedures, 
there is no risk of physical injury to participants. 
 
The process of collecting a dried blood spot sample is relatively painless and non-
invasive; however, participants may face minimal discomfort when completing 
this procedure. Prior to the dried blood spot sample collection, participants will be 
informed that the procedure may involve mild, temporary pain at the finger prick 
site and will be provided with suggestions for minimizing any pain that is 
bothersome (e.g., putting ice on the site). Participants will be sufficiently trained 
by study staff in how to self-collect their blood samples at home. Participants will 
be given the option to opt out of any dried blood spot collection points, for any 
reason. Participants who oppose the provision of dried blood samples will not be 

excluded from additional study procedures. In our previous study, it was common 
for ACS patients to already have experience using the blood spot finger-prick 
technique for their healthcare and almost all participants expressed comfort and 
willingness to complete this procedure as part of a research study.  
 
b. Drug side effects and toxicities 
There are no drug side effects or toxicities associated with this study.  
 
c. Device complications and malfunctions 
There are no risks of device complications.  
 
d. Psychosocial risks 
Patients may experience discomfort from completing the survey questionnaires or 
exit interview and/or participating in the intervention mindfulness trainings or 
discussions. Participants who do not find the study to provide a benefit to them 
may find this upsetting as well. All possible measures will be taken to ensure 
patient comfort and participants will be informed that they could exit the study at 
any point with no penalty. The PI (licensed clinical psychology) will be available 
while intervention groups are being conducted to intervene if needed (due to 
patient discomfort or to answer specific questions about the study). Participants 
will be informed that they can choose not to complete any surveys or answer any 
specific survey items or exit interview questions that make them feel 
uncomfortable, and that they do not need to complete the blood spot procedures. 
All of these procedures are consistent with sound research design and do not 
unnecessarily expose subjects to risk. 
 
The main psychosocial safety concern related to patients in this study is 
worsening depression symptoms and/or suicidal ideation. Subject safety regarding 
mood and suicidal ideation will be ensured in several ways. 
First, eligibility criteria require that patients do not have active suicidal ideation at 
the time of enrollment, and that they have not been hospitalized for a psychiatric 
reason in the past year. Thus, it is not likely that participants will report active 
suicidal ideation during or following the intervention. Moreover, our eligibility 
criteria require only minimal depression symptoms and thus we do not expect to 
have a severely depressed sample. 
During the eligibility screening procedures, participants will be administered the 
Patient Health Questionnaire-9 (PH-9) over the phone. If any patient endorses 
suicidality (i.e., PHQ-9 item 9 score above 0; “Over the past two weeks, how 
often have you been bothered by thoughts that you were better off dead or of 
hurting yourself in some way”), the RA will follow our standardized safety 
assessment protocol that our team has developed and used in prior funded studies 
of ACS patients with elevated depression symptoms. The protocol involves 
further assessing safety risks through a series of structured questions, with 

specific instructions at each step based on the patients’ response. It begins by 
clarifying the response to PHQ-9 item 9 (i.e., determining passive versus active 
suicidality). If patients endorse active suicidality, the RA will further assess safety 
risks (e.g., plan, intent, past suicide attempts) and immediately notify the PI (a 
licensed clinical psychologist) to conduct further assessment. The PI will conduct 
detailed suicide assessment of patients with active suicidality and inform the 
patient’s primary treatment providers of the patient’s symptoms and assist with 
the obtainment of further evaluation and care as needed (e.g., through referral to 
outpatient treatment or to the emergency department [ED]), depending on the 
urgency of the situation. In our previous work, it has been extremely rare for an 
ACS patient to report active suicidality that requires intervention.  
Upon enrollment, the RA will also conduct proactive safety planning with all 
participants in the following ways: (1) asking participants to identify 1-2 safety 
contacts that we would contact in the event that participants become at risk, (2) 
working with participants to identify the emergency department nearest to their 
home; (3) and instructing patients to go to this emergency room if they feel 
unsafe, and inform research staff once they are in a safe place (e.g., hospitalized 
or back at home). Participants will be asked to report any worsening symptoms to 
the interventionist during sessions, or in between sessions by contacting the study 
RA. 
For enrolled participants, the PHQ-9 will be administered at baseline, post-
intervention, and 3-month follow-up, which will allow us to monitor for 
worsening depression symptoms. The RA will review changes in participant’s 
PHQ-9 scores over time and contact the participant to discuss any concerns, 
asking about their symptoms, needs, and concerns about staying in the study, and 
conducting an initial safety assessment as needed (as described above). The same 
procedures as described above will be followed if participants endorse suicidality 
on PHQ-9 item 9 when completing the measure as part of any of the surveys. 
REDCap will be set up to send automatic alerts to the study staff for any PHQ-9 
item 9 responses greater than zero. Participants will be contacted within 24 hours. 
The interventionists for each group will observationally monitor participant’s 
symptoms during each weekly intervention session. If the interventionists become 
concerned based on a participant’s presentation during a session (e.g., per their 
clinical observation or expressed SI by a participant), they will call the participant 
by phone individually immediately after the session to check in about the 
participant’s symptoms and conduct a safety assessment if needed (following the 
protocol outlined above). The interventionist will be a licensed mental health 
provider trained in conducting safety assessments. Interventionists will instruct 
patients at the start of the first session that if they experience suicidal thoughts or 
worsening depression symptoms at any point during the study, they should let the 
interventionist, study staff, and/or their doctors know. 

The objective criteria for removal from the study is worsening psychiatric 
symptoms that become psychiatrically unstable that precludes their participation 
(e.g., constitute danger to self or others). The RA and interventionist will inform 
the PI of any concerns about a participant’s symptoms and about any contact with 
participants regarding these concerns. They will let the participants know that if it 
seems unsafe for them to remain in the study, the PI will contact them. In cases 
where depression symptoms are worsening but do not constitute necessary 
removal from the study, the PI will discuss the concerns with the participant, give 
them the option to exit the study if they would like, and assist them in connecting 
to a higher level of care if needed (e.g., by providing mental health referrals).  
Participants will be provided with an outline of resources for accessing mental 
health care at the completion of the study.  
e. Radiation risks 
There are no radiation risks associated with this study.  
 
VIII. POTENTIAL BENEFITS 
a. Potential benefits to participating individuals 
Participants may not benefit from this study. It is hoped that the intervention will 
result in improved scores on depression symptom measures. The current study 
may provide training in coping skills for managing depression and improving 
health behaviors, and promote understanding of depression and cardiac health. It 
may also provide emotional benefits for participants to share and receive support 
with their peers and a trained clinician. 
 
b. Potential benefits to society 
Developing targeted, efficacious, and accessible interventions to treat depression 
in ACS patients may have important public health benefits. Depression is 
common and deadly among acute ACS patients with up to 45% experiencing at 
least mild depression symptoms. Even mild depression symptoms double the risk 
of death in ACS patients.  Mind-body interventions that are accessible and 
address the underlying pathophysiology of comorbid depression and 
cardiovascular disease are needed, and the MBCT intervention being tested in the 
current stay has the potential to address this need. This study will establish the 
feasibility and acceptability of the intervention and inform targets for refinement 
in a future R01 efficacy trial. Thus, participation in this study may result in the 
development of an innovative, efficacious, and accessible depression treatment 
that can have substantial benefit to future ACS patients.  
 
 
IX. 
MONITORING AND QUALITY ASSURANCE 
a. Independent monitoring of source data 
Source materials will include information collected from survey questionnaires at 
baseline, post-intervention, and 3-month follow-up; exit interviews; weekly 
practice logs; post-session surveys; and blood spot collection procedures. All self-

report questionnaires will be entered electronically via REDCap. Individual exit 
interviews will be conducted by phone or videoconferencing. Upon their receipt, 
all dried blood spot samples will be stored securely in an MGH affiliated lab, on 
the MGH campus. Samples will later be shipped, in accordance with MGB and 
CDC guidelines, to our collaborators Dr. David Victorson and Dr. Thomas 
McDade at Northwestern University for storage and/or processing. All samples 
will be labeled with the patient ID, date of collection, group assignment, and time 
point (baseline, post-intervention, 3-month follow-up). We will follow all CDC 
shipping guidelines (e.g., placing a freeze pack inside of an insulated shipping 
container, placing sealed plastic bags containing the samples into a box). We will 
seal the box tightly with tape and ship specimens via courier to Dr. Victorson’s 
Consciousness in Health Lab at the Northwestern University Feinberg School of 
Medicine. 
Dr. Victorson will securely store the samples in his locked lab at Northwestern 
before bringing them for processing to his collaborator Dr. Thomas Dade at the 
Laboratory for Human Biology Research at Northwestern University. The blood 
samples will not contain identifiers that could be used by the outside collaborators 
to link the data to individual subjects; they will be labeled with participants’ study 
ID numbers and not any personally-identifying information, and only Partner’s 
study staff will have access to the data file linking participant’s personal 
information to their study ID number. Study staff have completed CDC and 
HealthStream trainings on dried blood spot storage and shipping and have 
acquired the proper documentation to ship samples to a non-MGB lab.  
All information collected will be for the purposes of research and will only be 
accessible to study staff and stored securely on the Partners’ network. Survey and 
practice log data will be reviewed for completeness though participants will be 
allowed to skip any questions they are not comfortable answering.   
 
b. Safety monitoring 
The principal investigator is responsible for data and safety monitoring. If study 
staff becomes aware of any adverse events, the event will be reported 
immediately to the PI.  
 
c. Outcomes monitoring 
 
Outcomes will be monitored via scores on self-report questionnaires at baseline, 
post-intervention, and 3-month follow-up. Participants will also be monitored 
during weekly MBCT and health enhancement control sessions. Study staff 
(licensed clinical psychologist, LCSW) will be available to respond to any 
worsening in outcomes. REDCap will be automated to inform the RA and PI of 
any endorsements of suicidality, so that the study team can follow up with these 
patients immediately.  
 

d. Adverse event reporting guidelines 
 
All PHRC guidelines will be followed with respect to reporting unanticipated 
problems, including adverse events. Specifically, when a serious or non-serious 
adverse event occurs, the PI will review the event to determine if it was possibly 
or definitely related to participation in the research. For all unanticipated 
problems and adverse events deemed related or possibly related to the research, a 
member of the research team will complete and submit an Other Event report 
through Insight/eIRB as soon as possible and within 5 working days / 7 calendar 
days (as defined in the March 2014 Reporting Unanticipated Problems Including 
Adverse Events report). At Continuing Review, a summary of all unanticipated 
problems will be provided as per PHRC protocol. Finally, if there are 
unanticipated problems, especially if serious or recurrent, the PI will amend the 
protocol if it is deemed necessary to protect the safety and welfare of the 
participants. 
 
 
X. 
References