Mindfulness meditation (MM) is an element of the Buddhist traditions first introduced as a clinical intervention in western medicine by Kabat-Zinn [1]. Over the past 35 years, the practice has received significant interest in clinical and health psychology and, more recently, in neuro- and psychophysiology. A family of meditative practices based on mindfulness is commonly used as a psychological approach to mental illness and chronic pain (CP) management. Mindful breathing is central to the mindfulness practices and places an emphasis on paying nonjudgmental attention to one’s cognitive, emotional, and physical experiences while reorienting focus on breathing sensations to cultivate cognitive and emotion regulation and progressively relaxed states [2]. Mindfulness-based treatments have been shown to be effective in reducing symptoms of depression, anxiety, and chronic pain [3,4].

One proposed mechanism for mindful breathing benefits is the state relaxation effect mediated by parasympathetic vagus nerve activation because of its process of bringing awareness to breathing sensations while practicing acceptance of stressors such as worrying thoughts, negative emotions, and pain [5]. However, individuals with pain, depression, and anxiety disorders commonly share the physiological trait of a dysregulated autonomic nervous system (ANS), particularly with respect to parasympathetic stress recovery processes, which compromise vagal activation [6,7].

Rigid and inflexible types of mind wandering, such as worry and rumination, are typically seen in individuals with psychiatric illnesses [8,9] and chronic pain [10]. These stressors lead to prolonged physiological stress activation linked to health risks [6,11]. MM attempts to counteract unhealthy mind wandering by instilling present-oriented attention that is more conducive to appropriately rested and relaxed states in the absence of stressful demands [12]. Critical to the purported benefits of mindfulness is that the removal of stressful stimuli in the environment does not always coincide with a return to resting state. Physiological stress inevitably arises through pain, worry, rumination, and distressing emotions such as fear, anxiety, and anger. Patterns of worry and rumination are defined as perseverative stressors, as they are typically related to past or anticipated stressors [6]. Perseverative stress refers to persistent physiological stress that can linger for prolonged periods, sometimes subconsciously, creating an undertone of stress arousal and allostatic load associated with gradual and sustained withdrawal of vagal tone, quantifiable by low heart rate variability (HRV) [11]. Chronically low HRV is a sign that the ANS is sympathetically dominant, with persistent and excessive activation of the stress response that is less amenable to vagal-mediated parasympathetic recovery [6,11]. Mindfulness practice may be a key method to target the pathophysiological mechanism common to chronic pain, depression, and anxiety. Mindful breathing can enhance vagal activation through state relaxation effects, as multiple studies have shown that even brief mindfulness practice after stress significantly increases HRV [13,14]. This vagal-activating effect may have stress-relieving benefits for individuals with depression-anxiety symptoms [15]. With regards to pain, reductions in self-reported pain have been demonstrated in individuals practicing HRV-based biofeedback [16], and it has been theorized that increased vagal activation is connected to several analgesic mechanisms such as lowered systemic inflammation and inhibited pain-processing brain regions [17]. Thus, the vagal-activating treatment potential of a smartphone-based mindful breathing app may have clinical utility, given the strong research evidence associating low HRV and psychological [18] and pain conditions [7].

A potentially impeding factor for client populations in practicing mindful breathing is the demand characteristics of the silent, inwardly focused exercise that may naturally make them more saliently aware of their symptoms of depression (eg, rumination), anxiety (worry), and pain (sensations). Relatedly, a qualitative study has revealed experiential challenges to MM practice that must be addressed in clinical treatment contexts, including the fact that meditation is a difficult skill to learn and practice, and participants encounter difficult thoughts and feelings amidst practice [19]. This is all the more relevant to naïve meditators with pain, depression, and anxiety symptoms, making for a potentially challenging experience that discourages further MM practice.

Supportive training tools, such as smartphone apps, are widely used to receive audio guidance on MM, and evidence is emerging for their immediate and long-term effects on altering mood states [20]. However, few studies have investigated the clinical utility and physiological changes related to meditation-based smartphone apps [21]. Furthermore, audio instructions may not be readily applicable in participants with clinical symptoms as they may be more vulnerable to their mind-wandering effects amidst meditation practice. In 1 study, a computer-based mindful breathing task provided random audio tones during the practice to prompt participants to reorient attention to breathing sensations after pressing a button on the keyboard to indicate whether they had been paying attention to breathing or other experiences at the time of the tone [22]. The results showed higher instances of breath attention were correlated with increased HRV during the practice, suggesting a positive relaxation effect of the mindful breathing task. This paradigm could be effectively applied in a clinical context for individuals who may initially struggle to practice mindful breathing, such as those with chronic pain and severe depression-anxiety symptoms. Although multiple studies have shown that MM leads to HRV increases [13,22], there are no known studies that have investigated the effects of a smartphone-based mindful breathing task on HRV in individuals with chronic pain and severe depression-anxiety symptoms. One study provided naïve meditators training in the mindfulness technique of thought distancing using a smartphone app or traditional mindfulness practice without an app. They found significantly greater mindfulness and pleasantness and lower perceived difficulty associated with the smartphone app–based mindfulness practice compared with the nonapp conditions [23]. More investigations are needed to determine in what ways smartphone apps can be employed as an effective medium of delivering mindfulness training to vulnerable populations who are naïve to meditation.

A recent systematic review of mindfulness-related apps found over 500 apps in the marketplace, but only 23 were designed to provide mindfulness training, and they were largely focused on providing audiovisual guidance, timers, and reminders to practice [21]. The review revealed that only 1 randomized controlled trial (RCT) for a mindfulness app was underway at the time [24] and that, generally, there is limited evidence available for the efficacy of apps in increasing mindfulness [21]. Furthermore, the literature on existing mobile apps marketed for chronic pain reveals that, with few exceptions [25], they rarely adhere to scientific guidelines and that health care professionals are rarely involved in their development [26-29].

The aim of this study is to overcome some of the aforementioned limitations by designing an app with input from clinical researchers and empirically testing the app’s effectiveness in a sample of young adults with CP, anxiety, and depression. To cultivate mindfulness, a mobile-based Mindfulness Meditation app (MMA) was developed based on Burg et al’s [22] mindful breathing exercise that “assesses the participants’ ability to mindfully stay in contact with the bodily sense of the breath during an exercise aligned with breathing meditation” [22]. In lieu of verbal meditation instructions amidst practice, the task provides audio tones at random intervals to which practitioners respond by pressing keys to indicate breath (if they were attending to their breathing at the sound of the tone) or other (if they were attending to an experience other than the breath at the sound of the tone). This simplified task may be more suitable to beginner meditators and particularly those with various psychiatric and pain symptoms that make meditation practice more difficult [19]. In a previous pilot study of the MMA (VV Latman, MA, unpublished data, June 2017), participants with chronic pain and severe depression-anxiety symptoms randomized to the 12-min MMA task exhibited significant reductions in mood states of anxiety, anger, and overall distress.

This study will evaluate the psychophysiological effects of a smartphone-based MMA (12 min; Figure 1) for individuals with clinically significant symptoms of major depression or anxiety (DA) or chronic pain. Specifically, the study aims to examine parasympathetic activity using HRV (primary outcome) in groups of participants who self-report clinically significant symptoms of DA and CP and condition-free (CF) participants who do not meet our criteria for either. In addition, given the linkages between HRV and the following psychological processes within psychological and medical conditions, the study will also assess mind wandering and present moment awareness, mood symptoms, and breath focus before and after the intervention. All study groups will be randomized to an MMA (MMA+) condition or a MM condition without the app (MMA−) after a brief stress induction procedure.

Overall, 3 major hypotheses (1a, 1b, 2a, 2b, and 3) will be tested.

This RCT study was designed according to the 2010 Consolidated Standards of Reporting Trials statement (Multimedia Appendix 1) [30], reviewed and approved by the York University research ethics board (Human Participants Review Committee protocol number e2017-303), and registered with ClinicalTrials.gov (NCT03296007) on September 22, 2017, before the recruitment of the first participant. A total of 180 male and female participants will be recruited from the Web-based York Undergraduate Research Participant Pool, based on voluntary participation, and classified into 3 groups of approximately 60 participants each (and randomized into MMA+ or MMA−) based on their prescreening questionnaires: CP (n=30 MMA+ and n=30 MMA−), depression-anxiety (n=30 MMA+ and n=30 MMA−), and CF participants (n=30 MMA+ and n=30 MMA−; Figure 2).

Sample size estimate for a repeated-measures linear mixed-effects analysis of variance (ANOVA) with 3 groups (CP, DA, and CF), 2 conditions (MMA+, MMA−), and 3 phases (baseline, stress induction, and MM) indicates that a total of 141 participants are needed to detect small-to-medium effect size (f=0.15) HRV changes with a type I error rate (alpha) of .05, a power of 0.95, and a 0.50 correlation between repeated measures (G*Power; Heinrich Heine University Düsseldorf). The small-to-medium effect size corresponds to previously published studies of HRV increases during brief mindfulness practice [13,14]. Recruitment of more than 180 participants will allow for an attrition rate of approximately 20% because of withdrawals, dropouts, technical failures, and missing data. On the basis of prescreening and recruitment numbers in our past pilot study (VV Latman, MA, unpublished data, June 2017), we found the percentage of participants reporting diagnosed CP, severe depression, or anxiety symptoms to be 27%, 33%, and 41%, respectively. Accordingly, the combined number of students expected to be prescreened for eligibility to enroll 60 participants per group will be approximately N=550.

Participants will be eligible for the study if they are enrolled in a course at York University that provides course participation credit via study enrolment through the Undergraduate Research Participant Pool website. On the recruitment website as well as on the consent form, we have explained that the study may require use of a smartphone-based task. Participants with self-reported cardiac conditions (eg, cardiac arrhythmias, coronary artery disease, and pacemaker) will be excluded as they contravene the interpretation of vagal-mediated HRV [31]. Participants in this study will have no prior relationship with the researchers, including participation in classes by faculty members on the research team.

The MMA was developed using JavaScript and installed on an iPhone 4s. As the app was designed with young adults in mind, the leading thought was to keep the intervention brief and the design simple and easy to use. Participants are asked to hover their thumbs on 2 buttons, breath and other, presented on a white screen for the duration of the task (Figure 1). The MMA is a 12-min breath awareness task that involves a total of 24 silent phases comprising 6 different durations (5 seconds, 15 seconds, 25 seconds, 35 seconds, 45 seconds, and 55 seconds) randomly presented 4 times each and followed by the presentation of a 1-second tone. During the silent phases, participants are to practice mindful breathing with their eyes closed by paying attention to their breathing sensations and reorienting their attention when noticing their mind wandering. At the sound of the tone, participants press breath if, in that moment, they were attending to their breath, or other if they were attending to other experiences. Participants are instructed to return their attention to mindful breathing after pressing 1 of the 2 buttons on the screen. The app was designed to record reaction time from tone onset to button press and the number of times breath and other buttons were pressed. A prototype was first tested internally, and feedback was gathered from the research team and pilot participants to ensure a smooth user experience without technical bugs. Feedback influenced decisions regarding the number of tones and interval between tones played, the size of the breath and other buttons, and the addition of a 1-min trial period before commencing the 12-min meditation task.

Participants in the MMA+ condition will use the MMA to practice mindful breathing with the following instructions: “For the duration of the task, pay attention to your breathing sensations, including (1) the feeling of the air passing through your nostrils, (2) the movement of your in-and-out breath at your chest and torso, (3) the sound of the air as you breathe in and out, (4) the temperature (coolness or warmth) of the in-and-out breath, and (5) returning your attention to your breath when you have noticed your attention has been elsewhere.” In addition, amidst mindful breathing practice, they will be asked to press a breath (I am paying attention to my breath) or other (I am not paying attention to my breath) button on the phone screen when hearing a tone introduced at random intervals. The MMA task will involve a total of 24 silent phases of 6 different durations (5 seconds, 15 seconds, 25 seconds, 35 seconds, 45 seconds, and 55 seconds) randomly presented 4 times each and followed by the presentation of the tone. Participants are provided a 1-min practice session with the app before the intervention session. Participants will engage in smartphone-based mindful breathing for 12 min in a seated and eyes closed position.

Participants in the MMA− condition will engage in mindful breathing without use of the smartphone app for 12 min in a seated and eyes closed position.

This study has 2 coprimary hypotheses based on published recommendations for HRV analyses [31,39]. Generally, within-subject designs and analyses are preferred considering the high interindividual variations observed in HRV measures. To analyze differences in HRV with respect to MMA+ and MMA− between groups, change scores from stress to MM will be computed by subtracting stress-HRV from MM-HRV and used as the dependent variable in hypothesis 1a. In addition, within-subject changes in HRV according to the MM conditions and groups will be examined in hypothesis 1b. Results will be interpreted using significance values, confidence intervals, and effect sizes [51]. Intention-to-treat methodology will be the guiding principle of analyses. A complete case analysis approach will be used in anticipation of missing or unusable data.

Associations between HRV and psychometric measures will be explored with Pearson correlations and linear regression models using the following constructs: present moment awareness (PMARS), mind wandering (MWI), anxiety symptoms (Anxiety Sensitivity Index), depressive symptoms (CES-D), state mindfulness (TMS), and mindfulness skills (FFMS). Breath focus and reaction time will be examined for group differences (CP, DA, and C) using 1-way ANOVA. Given potential response biases in self-reported outcomes, we will examine group differences in socially desirable responding (SDRS-5) using 1-way ANOVA and use it as a control variable in applicable outcome analyses.

The main findings of the study are expected to reveal a positive pattern of HRV responses across the different study groups, CP, DA, and C, such that they exhibit significantly increased HRV (P<.05) in the treatment condition, MMA+, in comparison with the control condition, MMA−. On the basis of previous research published by our team, HRV is expected to increase during MM when practiced after stressor tasks [13,14]. However, a pattern of inflexible HRV responses has been noted in previous studies involving participants with clinical characteristics. For instance, a randomized experimental study of students high on perfectionistic traits and nonperfectionist students was conducted with measurement of HRV at baseline, stress, and during subsequent audio-guided MM or a rest condition with an audio lecture. Only the nonperfectionist group exhibited significantly increased HRV in the mindfulness condition, whereas the perfectionists did not, reflecting an inflexible state of sympathetic dominance [13]. A follow-up study was conducted with headache and headache-free participants where both groups showed increased HRV during post-stress mindfulness. However, during post-stress rest, the headache group exhibited significantly lower HRV compared with headache-free participants, reflecting impaired ability for cardio-vagal recovery [14]. This pattern of results is consistent with literature indicating low and inflexible HRV patterns in individuals with clinical characteristics of depression, anxiety, and chronic pain [52-54].

The MMA is designed as a supportive training tool to aid clinical populations with mindful breathing practice. Accordingly, our primary hypothesis is that HRV will increase from the stress to MM phases in DA and CP participants randomized to MMA+ compared with MMA−. Specifically, mindful breathing practice with the aid of the MMA is expected to yield additional relaxation effects for participants, by way of respiratory sinus arrhythmia, to be reflected in increased HRV measures. Examination of secondary hypotheses will help to further contextualize the role of key psychological processes, including present moment awareness, state mindfulness, mind wandering, and mood, as mediators and outcomes of mindfulness-based treatments.

A potential limitation of this study is the lack of blinding of research assistants with respect to group screening and treatment allocation procedures. Research assistants are required to remain in the room to address any technical or practical issues with the intervention, negating the possibility of blinding research assistants to treatment. However, both MMA+ and MMA− conditions entail app- or self-guided mindful breathing practice with no active involvement of research assistants; thus, risk of bias in intervention delivery is low. Another limitation is that the use of the MMA presents a demand characteristic requiring participants to reliably report breath or other responses. Any accidental responses by participants that do not correspond to their attentional states (eg, pressing breath when the intention was to press other) cannot be corrected during the MMA task, and may momentarily distract participants during the task. In addition, participants will only be provided 1 session of the MMA task, which is a limited duration of exposure that prevents examination of dose-response effects. In future longitudinal studies, we hope to test repeated practice with the app and its effects on HRV, pain, mood, and other outcomes. In terms of study groups, classification criteria did not exclude individuals who reported mild-to-moderate levels of depressive-anxiety symptoms or pain for less than 3 months, instead classifying subcriteria participants as condition free. The presence of symptoms in the CF group has the potential to impact results. With regard to study outcomes, it must be noted that the MWI and present moment awareness rating scales are awaiting psychometric validation and will undergo factor analyses based upon the data gathered in this and other studies. One procedural limitation is that the MMA− condition is not structurally identical to the MMA+ condition as it foregoes the use of a smartphone app during the practice of mindful breathing. To preserve task similarity, it may be useful in future studies of the MMA to provide participants with a control app that does not provide random-interval tones as they practice mindful breathing. Finally, the study is based on undergraduate student populations, limiting generalizability until future studies are conducted with community and clinical populations.

This RCT will contribute to the burgeoning health psychology literature about the clinical relevance of HRV measures in the assessment and treatment of psychiatric and health conditions. The findings may also contribute to the growing use of HRV as a biomarker and biofeedback tool within clinical and health psychology. Furthermore, there is an evolving need for an evidence basis related to supportive mindfulness training tools for the self-management of symptoms related to depression, anxiety, and chronic pain. The innovation of incorporating mindful breathing practice into a scalable app provides valuable information to allow for future iterative development of an app involving novel techniques for teaching mindfulness to clinical populations.