The PAPHIO study protocol: a randomised controlled trial with a 2 x 2 crossover design of physical activity adherence, psychological health and immunological outcomes in breast cancer survivors

Adoption and adherence to physical activity programs amongst cancer survivors are challenging due to their physical and mental vulnerability [19]. As such, in this study we developed an intervention which maximizes feasibility, sustainability and generalisability. This study will prescribe self-directed physical activity to breast cancer survivors. Many of self-directed techniques for physical activity adherence in participants with advanced stage of heterogeneous cancers have been used in research studies, such as partially advised and home-based program, exercise class teaching and peer support walking group programs [20]. Many of the programs have achieved high percentages of exercise adherence, reducing fatigue and improving QoL [20].

An important factor to adopt and adhere to a physical activity program is an individual’s motivation. To this end, a number of behavioural change strategies have been reported which enhance motivation and adherence [21]. Two of these strategies are Motivational Interviewing (MI) and self-monitoring. MI is a conversation technique used by a professional during consultation when making health behaviour changes [22], and has been effectively used to bring about behavioural change in health promotion programs for the general population. This includes changes in eating behaviour, alcohol cessation and adoption of an active life style [23]. More specifically, face-to-face and phone based MI has been implemented successfully to enhance self-efficacy and reduce resistance against physical activity in breast cancer survivors [24, 25].. On the other hand, self-monitoring,one of the important concepts in self-regulation theory, is an auditing mechanism of individual performance in relation to an individual’s cognitions, beliefs and emotions [26]. Some digital devices have the ability to promote physical activity through self-monitoring concept [27]. For example, step counting gadgets including pedometers, can effectively monitor physical activity in terms of daily steps. Such devices have been utilised for promotion of physical activity in clinical trials [28] especially in breast cancer patients and survivors [29, 30]. Step counters help in monitoring individual’s physical activity behaviour and can result in increased motivation and ultimately adherence to long-term physical activity behaviour [31].

To understand participants’ motivation to self-directed physical activity, self-determination theory (SDT) has been effectively used to enhance insight in physical activity behaviour and motivation in breast cancer survivors [32]. According to SDT motivation to engage in behaviour lies on a continuum ranging from extrinsic (controlled by external factors) to intrinsic (individual interest and preference). The theory predicts that intrinsic-motivation might enhance confidence in task accomplishment (competence), independent action (autonomy) and the feeling of connection to others (relatedness) [32]. Our study will assess how self-regulation and motivational interviewing might change participants motivational orientation over the intervention period using the behavioural regulations in exercise questionnaire (BREQ2 [33];).

Self-efficacy, an important concept in social cognitive theory, has been shown to be a predictor for physical activity behaviour and adherence in breast cancer patient [34]. In this project two types of efficacy beliefs will be examined. First, we will explore exercise barriers self-efficacy, which will examine the participants’ confidence to overcome or deal with barriers to their exercise participation. Secondly, this project will examine task self-efficacy beliefs In particular, it will examine the self-efficacy beliefs of the participants to engage in exercise behavior [34]. To measure this, the project will use the nine-item barriers self-efficacy [34] and four-item task self-efficacy questionnaire [34].

The study has an overall aim to determine the effects of 24 weeks self-directed activity combined with motivational interviewing on (i) psychological health (depression, anxiety, stress), (ii) quality of life (QoL; physical, social/family, emotional and functional) and (iii) immune function in female breast cancer survivors. In addition, we will explore the dose-response relationship between exercise volume (step count) and the outcome measures.

This study is a randomised crossover trial; a single site research project conducted at Brest Cancer Service Clinic, Western Health (Sunshine Hospital) Australia. Potential participants will be prescribed with a Fitbit Alta HR tracker for a 24-week-self-directed activity and will receive motivational interviewing for 12 weeks (Immediate intervention group; during week 0 to week 12 and Delayed intervention group; during week 13 to week 24). The study protocol through 24 weeks is illustrated in Fig. 1.

The study will recruit participants who are breast cancer survivors within 3 years of diagnosis and at least 6 months post primary treatments. Eligible participants will be randomly allocated to immediate intervention or delayed intervention groups in a 1:1 ratio after completion of informed consent. The participants will be recruited from Breast cancer care service, Western Health Sunshine campus in Melbourne. Recruitment strategies will include public media (poster advertising or flyer) and individual contact introduced by their physician [35]. All participants have to be approved by their physician for engagement in the physical activity program of this research and the screening process will be conducted before obtaining consent.

The study will commence at Western Health Sunshine campus following ethical approval from Melbourne Health Human Research Ethics Committee (MH HREC) and Western Health research governance authorization [36]. Based on our power calculation we aim to recruit 64 participants.

The study design is a two-armed RCT with a crossover design. Sequence generation will be conducted by simple randomisation following patient informed consent. The participants will be randomly allocated to either IIG or DIG in 1:1 ratio by computerised number generator. Allocation concealment by enclosing the allocation in sealed envelopes will be used to prevent selection bias [37]. The allocation concealment will be conducted by a third party to prevent researchers from affecting group assignment. The participants in both groups will be prescribed a self-directed physical activity for 24 weeks. The IIG will receive MI from week 1 to week 12, whereas DIG will receive the same MI intervention from weeks 13 to 24.Allocation concealment technique will be applied in process of randomisation. During weeks 1 to week 12, theIIG will perform self-directed physical activity and receive MI. On the other hand, the DIG will perform self-directed physical activity without MI. During week 13 to week 24, DIG will continue self-directed physical activity with MI. Whereas IIG will perform physical activity but will no longer be given MI.

Participants will perform a 24-week period of self-directed, pedometer controlled physical activity [38, 39]. All participants will be given a step-count tracker devise (Fitbit Alta HR) and investigators will explain the prescribed pedometer-based activity to participants. Fitbit Alta HR is a wearable gadget and can be used to monitor step count. The participants’ activity engagement will be accompanied by individual face-to-face and phone call MI [22]. Participants will be taught how to operate the Fitbit and will be taken on a 10 min walk to experience a moderate level of exertion.. At week 1 (baseline or T1), all participants will be prescribed to assess and record their activity using the Fitbit monitoring device through its application via computer or smartphone to establish their baseline physical activity volume by step count. Following this, they will be advised to perform their activity on their own pace as tolerated and will wear the Fitbit during the daytime or when they are available for physical activity throughout the 24 weeks. Individual participants will be advised and motivated to gradually increase their daily steps on physical activity at moderate intensity exertion or at their perception of taking some efforts but can talk during physical activity (the recommendation by the department of health, Australian government) [40] during face-to-face and over the phone MI. The participants will be advised for safety during physical activity. They will be suggested to stop physical activity if adverse symptoms occur such as chest pain or pain down to arms, dizziness, difficulty breathing, unusual rapid heart rate, and sever fatigue. The researcher will suggest to the participant to inform their family members and take a mobile phone with them before they go out to exercise. They will be also advised to take record of their daily steps in their notebook. All participants will be informed that the researcher will track the participants’ step count and tracker usage time via Fitbit connect application. Individual average daily step count, and activity level will be assessed at baseline (T1), week 12 (T2), and week 24 (T3).

MI will be used in encouraging participants through open-end questions, friendly and supportive communication and induction of behavioral changes [22, 24]. Each MI will be conducted through four phases of conversation comprising: 1) Engage, 2) Focus, 3) Evoke, and 4) Plan [22]. The study will use the dialog of MI guided by Mentha Counselling and will be conducted by a counsellor who experienced MI There will be a 20 min face-to-face in week 1 and three phone MI sessions (15 min) at weeks 2, 4 and 9 for IIG. For DIG this will take place at weeks 12, 13, 15 and 20.

Approximately 20 ml of blood will be collected via a venipuncture at T1, T2 and T3 for both groups. Whole blood will be collected into a tube containing anticoagulant and centrifuged immediately after collection or on the same day approximately 7 h later.

Isolation of peripheral blood mononuclear cells (PBMCs) by density gradient configuration using Ficoll-Paque will be used for immune cell functions. PBMCs will be stored in refrigerator not longer than 1 day and then use flow cytometry to assess the composition of the isolated PBMC populations.