Our study plans to examine how MBCT delivered via the web may affect primary and secondary outcomes for individuals with a history of depression. It will also assess mediators, moderators, and the sustainability of the intervention. The following hypotheses will be assessed among program participants in the intervention group as compared to a waitlist control group, and within groups compared from pre- to postintervention.

Using a waitlist control design, this trial will randomize 128 eligible participants into 2 groups. In the first phase lasting 8 weeks, group 1 will partake in the MBCT intervention plus treatment as usual (MBCT + TAU) while group 2 will remain as waitlist control following TAU. In the second phase lasting 8 weeks, group 2 will begin completing the MBCT intervention, and group 1 will enter a follow-up phase, continuing with TAU. TAU will be comprised of psychotherapy, pharmacotherapy, or a combination of both. Data collection will be completed at baseline, 8 weeks (postintervention for group 1 and preintervention for group 2), and 16 weeks (follow-up for group 1 and postintervention for group 2). In this manner, our study design will ensure that both trial arms are treated fairly, and that group 1 can be followed up for 8 weeks to assess the sustainability of the intervention. Figure 1 outlines the flow of this study. The registration of this trial took place on April 22, 2022.

This study will conduct data collection at 3 different time points: TI—baseline, TII—postintervention for group 1 and preintervention for group 2 (8 weeks), and TIII—follow-up for group 1 and postintervention for group 2 (16 weeks). Participants will complete web-based self-reported surveys administered via Qualtrics (Qualtrics). If the participant prefers, paper surveys will be administered. Figure 2 lists study measures and assessment points.

The total sample size of our trial is expected to be 128 individuals with 64 participants placed into each group. This was estimated by a 2-tailed t test using GPower 3.1 (Informer Technologies, Inc) software. Our calculation of sample size depended on (1) the level of significance (α error probability), which was set as .05 based on Ronald A Fisher’s suggestion [55]; (2) the expected effect size, which was set as d=0.5, according to Cohen classification that “a medium effect of .5 is visible to the naked eye of a careful observer” [56]; (3) the expected power of this study (1–β error probability), which was set as 0.8 based on Cohen theory [57] because we failed to obtain support from previous similar studies; and (4) the allocation ratio (N2/N1), for which we expect number of participant in treatment group and control group to be the same.

Consenting participants will be randomized 1:1 to either group 1 or group 2 via the randomization function found in Qualtrics. This will be conducted by the principal investigator (PI). Once the number of participants has reached 7-12 individuals for both group 1 and group 2, this study will commence. This will proceed continuously until the expected sample size of 128 individuals is reached, or 4 years have elapsed. The implementation of this process will be overseen by the clinical research team.

Blinding in this type of study is not possible, as knowledge of the group assignment to the participants and providers will be evident. However, to minimize bias in this study, the investigators as well as data analysts will be masked from the respective assignments of the intervention group and TAU group. Blinding will only be terminated after all data collection and analysis have been completed.

It is possible that participants who choose to participate in this study could be more motivated than those who choose not to participate. Participants who are lost to follow-up after randomization could also affect the comparability of the groups.

This study was approved by the Institutional Review Boards (IRBs) at Greenville Health System and Clemson University (1852922; Pro00092709). All participants will provide written informed consent before participating in this study. This will be collected and safely stored by one of the clinical data collection team members.

The IRB at Clemson University and Prisma Healthcare System have approved this study. Some of the topics we will discuss are personal and may be upsetting to some participants. If participants experience distress and need treatment, a licensed clinical psychologist or psychiatrist will be contacted immediately. If required, we will provide a list of referral sources for participants who need additional treatment. In the event of physical injury, we will follow emergency procedures for the facility from which the participants are recruited. If an adverse event occurs, a member of the research team will reach out to the affected participant within 24 hours. Subsequently, a meeting will be convened by the research team to discuss the cause of the adverse event and if any modification to this study needs to be made. If any modification needs to be made to the trial protocol, a formal amendment will be submitted to the IRB for approval.

By the National Institutes of Health Office of Human Research Protection, the research team has constructed the Data and Safety Monitoring Plan, safeguarding the well-being and privacy of study participants. Recruitment and safety data will be regularly reviewed by the monitoring board comprised of members from Prisma Health System and Clemson University. Using a personal code that is only accessible by the PI, each participant’s demographic data, and outcome measures will be linked and stored for data analysis. No other identifying data relating to the participant will be linked to these codes. If there are data that are missing, these will also be a component of the monitoring plan for statistical analyses. Every quarter, the board will convene to assess any adverse effects, and on an annual basis, the board will discuss the audition of trial conduct. If the trial needs to be halted, and after consulting the data monitoring committee, the PI will make the final decision to stop all trial proceedings.

The clinical data collection team will receive training from a licensed clinical psychologist on appropriately gathering data from the PHQ-9 [42] forms to ensure the validity and reliability of trial data. All data collected will be stored electronically and encrypted to ensure confidentiality. This will be done at the clinical facility at which the data are collected. The PI will have full access to the trial data set. To promote the retention of participants, intervention facilitators will encourage continued participation in MBCT sessions, providing the stage to voice any concerns that may have arisen. If concerns arise regarding participation, a member of the research team will reach out to that participant to encourage them to remain.

The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) reporting guidelines [61] were used in the editing of this paper.

A core aim of this study is to supply the field of research concerning the effect of MBIs on depressive symptoms. To achieve this, we will first address the feasibility and efficacy of delivering MBCT to adults with depressive symptoms via a model delivered via the web. Our unique method of implementation will be tested via a randomized controlled trial with objective markers of depressive symptoms, an adequate overall sample size, and the assessment of adherence and feasibility. Additionally, we will be able to continue postintervention follow-up for 8 weeks, adding to the literature on whether gains can be sustained over time. It is important to assess the capability of MBIs to exert similar effects via web-based formats, as the ability to deliver web-based interventions improves accessibility and affordability of treatment. As such, these interventions may have a broader reach and be used in complement to formal mental health treatment.

Next, we will contribute to the evidence base regarding MBCT’s efficacy in reducing depression symptoms and psychiatric distress. Although pharmacotherapy is widely used and upholds its role in the management of depression, it can be accompanied by medication side effects, delayed onset of therapeutic effects, a lessened impact on milder forms of depression, and an inability to show efficacy in treatment-resistant depression [62]. Furthermore, improper discontinuation of antidepressive medications runs the risk of medicine withdrawal symptoms, and even in the presence of proper medication cessation, there may be a risk of rebound or relapse in depression after discontinuation of antidepressants [63]. Consequently, more evidence supporting MBCT’s role as an adjunct or primary therapy in depression management will be imperative for both clinicians and patients.

We also hope to examine the impact of MBCT on secondary outcomes, including perceived stress and facets of mindfulness. There is increasing evidence in support of perceived stress being positively correlated with the risk of developing depression [64,65]. This may be due to increased activity in the superior frontal gyrus which plays an important role in emotional regulation and cognitive control, with higher spontaneous activity in this region being possibly associated with psychopathologies such as MDD, posttraumatic stress disorder, and social anxiety disorder [66]. If MBCT has a positive impact on perceived stress, this study will add to the understanding of the causal pathway between MBCT, perceived stress, and depressive symptoms. Similarly, given that facets of mindfulness are inversely correlated with components of depression [67], this study can add to the evidence supporting the role that MBCT may play on that causal pathway also.

Through measurement of the extent of mindfulness self-practice and executive function, we hope to better understand the causal pathways between MBCT and depression symptoms. The positive effects of mindfulness practice have been purported to follow a dose-dependent pattern. This may be due to increased functional connectivity within various brain regions [68]. As such, it would be important to assess the role of mindfulness self-practice outside of the dedicated intervention time and its effects on depression. Finally, executive functioning has been shown to have an important influence on emotional regulation abilities [69,70]. The application of MBIs has been shown to be a viable means of improving certain aspects of executive function [71]. Thus, examining executive functioning could provide important insight into MBCT’s ability to influence emotional regulation and depression symptoms.

We will also be able to look at moderators and correlates of intervention outcomes, such as intervention adherence and mental health history, to determine factors that could improve or detract from intervention success.

Overall, this study will generate valuable insights elucidating the possibility of future studies with larger scopes and more elaborate study designs. These may consist of multiple evidence-based comparisons and longer postintervention follow-ups.

Recruitment for the trial began in December 2022 and will last approximately until the sample size of 128 individuals is reached or 4 years have elapsed (September 2026).