Study setting {9}
Recruitment and screening of participants will be conducted across the primary health care centres in five regions in Sweden: Norrbotten, Västra Götaland, Östergötland, Stockholm and Örebro. Details on study sites can also be found in ClinicalTrials.gov Identifier: NCT04219800, 2nd of Jan, 2020.
Eligibility criteria {10}
This study will focus on individuals at an increased risk for diabetes complications. Inclusion criteria are: diagnosed with T2DM, aged 40-64 years, BMI ≥ 25 kg/m2, HbA1c 53-100 mmol/mol (7.2-11.3 %) and working at least 75% in a mainly sedentary occupation (performing > 50 % of duties while sitting). Exclusion criteria are: pregnancy, regular high-intensity physical training more than 75 minutes/week, severe immobility or other obstacles to complete the protocol.
Who will take informed consent? {26a}
The regional coordinating investigator or his/her designee will give eligible participants a detailed oral and written description of the study. An opportunity to ask questions will be provided before the written informed consent is obtained.
Additional consent provisions for collection and use of participant data and biological specimens {26b}
Not applicable.
Interventions
Explanation for the choice of comparators {6b}
We will evaluate whether mHealth (activity tracker and SMS-reminders) reduces sitting time, increases steps and provides health benefits compared to counselling and telephone follow-up by a diabetes specialist nurse alone.
Intervention description {11a}
Intervention arm
The intervention will begin with individual face-to-face counselling with a diabetes specialist nurse who will use a patient-centred approach focused on occupational sitting (25,29). Results from the baseline one-week activity measurements with thigh-worn accelerometer (activPAL3) will be used for reflection over daily activity patterns. Individual strategies to reduce occupational sitting and stepwise goal setting will be discussed and written down on a goal sheet (22,30,31). Participants will receive written and oral instructions to interrupt prolonged sitting. Interruptions will be gradually increased to three minutes every 30 minutes of either simple resistance activities or low intensity walking (6). Telephone follow-ups take place after one and five weeks. Participants will also receive additional support for mobile health technology. They will use an activity tracker wristband, Garmin Vivofit4 (Nordic Garmin Sweden AB Billdal) that prompts the participant when he/she has been continuously inactive for more than 1 h. Visually, a red ’move bar’, and auditory, delivers a low short beep, prompts will be received (22). To reset the ’move bar’, participants need to walk for a couple of minutes. The activity tracker automatically creates a step goal based on previous activity levels and informs the user when the daily goal is reached. Participants will also receive regular SMS text reminders on the workdays, either daily or weekly depending on personal choice. SMS text reminders will include a link to a mobile video instruction for simple resistance activities (26).
Comparator arm
Participants in the comparator arm will only receive individual face-to-face counselling and telephone counselling with a diabetes specialist nurse who will use a patient-centred approach focused on occupational sitting (14,19).
Criteria for discontinuing or modifying allocated interventions {11b}
The participants can withdraw from the study at any time.
Strategies to improve adherence to interventions {11c}
During the trial period, all the study participants will have individual face-to-face appointments with the diabetes specialist nurse at 0, 3 and 12 months (Fig 3). To improve adherence to the protocol, telephone follow-ups will occur one and five weeks after the face-to-face appointment.
Relevant concomitant care permitted or prohibited during the trial {11d}
Study participation does not replace the usual diabetes care. The usual care in Sweden often involves a multidisciplinary team approach and comprises care by the primary care practitioners, diabetes specialist nurses, and nutritionists and ophthalmologists when required.
Provisions for post-trial care {30}
There will be no provisions after this trial.
Outcomes {12}
All primary and secondary outcomes will be measured at study visits at three time points: 0, 3 and 12 months (See also Participant Timeline Fig 3).
Primary Outcome
Sedentary time and physical activity
Increased physical activity at work may lead to increased sitting time or fewer steps outside working hours (32). To account for such possible compensatory effects of the intervention, total sitting time (minutes per week) and total steps (steps per week) were chosen as primary outcomes.
Secondary Outcome
The secondary outcomes are fatigue, health related quality of life, cardiometabolic risk, number of sick leave days, medications and musculoskeletal problems.
Other Outcomes
Occupational sitting time (minutes per week) and occupational steps (steps per week) will be evaluated in a secondary analysis.
Self-efficacy will be evaluated as an effect modifier of changes in sitting time and steps.
Participant timeline {13}
Sample size {14}
The sample size is calculated based on the difference in daily step counts using a mHealth intervention pilot study (15 participants) (26). Based on an increase of 1496 (Standard deviation=2930) steps/day after 3 months, and incorporating a dropout rate of 15%, a total of 142 participants would have 80% power in finding a statistically significant difference in step count between the groups. Approximately 1500 steps/day can also be translated to additional 15-25 minutes of daily walking (depending on walking speed) which we deem as a clinically meaningful difference for physically inactive T2DM patients (33).
Recruitment {15}
The recruitment strategy will include: a) personal communication at diabetes check-ups with diabetes specialist nurses, b) written invitation and/or invitation via telephone to potential participants using local diabetes patient registers, or c) through advertisement using e.g. posters and media adverts.
Assignment of interventions: allocation
Sequence generation {16a}
Participants were block randomized by a computer-generated sequence (to counteract the imbalance between the centre and skewed sex ratio) into either the intervention or the comparator arm. Randomization will be done after baseline measurements at a ratio of 1:1.
Concealment mechanism {16b}
Not applicable.
Implementation {16c}
After both participants and employers have given written informed consent. Participants are registered in REDCap (Research Electronic Data Capture). REDCap creates a study identification number for all the participants. Randomization is conducted in REDCap. A diabetes specialist nurse or research nurse will enrol the participants and assign participants to interventions based on the randomization.
Assignment of interventions: Blinding
Who will be blinded {17a}
Researchers responsible for statistical analysis will be blinded with regards to the group allocations. The diabetes specialist nurse and laboratory staff will not be blinded.
Procedure for unblinding if needed {17b}
Not applicable.
Data collection and management
Plans for assessment and collection of outcomes {18a}
Demographic data
Information on age, sex, country of birth, education, marital status, occupation and tasks assignment/duties, current smoking status, working hours and alcohol consumption will be self-reported. Total use of medications and eventual changes in medications will be collected from the patient records as well as a participant diary during the study period. Diabetes complications and duration as well as other chronic diseases are collected from the patient records. Participants keep diary on sick leave days during the study period.
Sedentary time and steps
Total and occupational sitting time (minutes per week) and total steps (steps per week) will be measured with a thigh-worn, activPAL3™ accelerometer (PAL Technologies Limited, Glasgow, UK). The accelerometer will be worn for 24 hours per day for 7 consecutive days (23). The device is initialised using manufacturer’s software with the default settings (i.e., 20Hz, 10s minimum sitting-upright period) and will be covered in a nitrile sleeve and fully wrapped in waterproof dressing to allow participants to wear the device during bathing activities. Participants will keep a diary on their working days and working hours.
Biochemical variables
HbA1c and lipids (serum total cholesterol, HDL cholesterol and triglycerides) will be assessed using standard laboratory methodology.
The health benefits of reduced sedentary behaviour are likely mediated by several mechanisms. The results will, therefore, be weighed together in a clustered cardiometabolic risk score (CCMR) (34). CCMR will be determined by summing z-scores ([value−mean]/standard deviation (SD)) of waist circumference (cm), mean arterial pressure (mmHg), HbA1c (mmol/mol), the inverse of HDL (mmol/L) and triglycerides (mmol/L), using sex-specific means and SDs based on previous studies (34,35). The use of a common mean and SD for standardised variables at two time points ensures that changes in the score can vary from zero. We will divide both by 5, separately, to account for the number of variables included. Change in the CCMR will be calculated by subtracting the follow-up CCMR from the baseline CCMR. Mean arterial pressure provides a better representation of the average pressure throughout a single cardiac cycle and will be used instead of systolic and diastolic blood pressure. Mean arterial pressure will be calculated using the formula (systolic pressure + [2 × diastolic pressure]/3) described as being one third of the distance between the systolic pressure and diastolic pressure (35).
Anthropometric data
Height and weight are measured without shoes, to the nearest 0.1 kg for body weight and to the nearest 0.1 cm for height. BMI is calculated as weight (kg)/height (meters²). The blood pressure will be measured after a 5-10 minutes rest, sitting on the chair with both feet on the floor and always in the same arm. The average of two readings are recorded for systolic- and diastolic blood pressure. Waist circumference is measured in a standing position with a tape measure to the nearest 0.5 cm at the level midway between the lower rib margin and the iliac crest during a light exhale. Waist circumference is measured twice and if there is a difference > 1 cm the measurements are repeated otherwise a mean value is counted to the nearest 0.5 cm. The same measuring tape will be used during the whole study period.
Health related quality of life
Health-related quality of life will be measured by the RAND-36 (26). The Swedish translation of the RAND-36 is conceptually equivalent to the English version (27).
Fatigue
Fatigue will be measured using the four item General Fatigue subscale of the Multidimensional Fatigue Inventory-20 (MFI-20) (28). MFI-20 is a self-reporting and validated test, incl. the Swedish version (29). MFI-20 is a 20-item multidimensional tool that uses a Likert-type scale from 1 to 5, with total scores with range 4-20. MFI-20 contains 5 subscales: General Fatigue, Physical Fatigue, Reduced Motivation, Reduced Activity, and Mental Fatigue (28).
Musculoskeletal problems
A numerical rating scale (NRS) questionnaire will be used to measure pain intensity (30). The scale has 11-points (i.e. 0–10) with 0 meaning ‘No pain’ and ‘10’ meaning ‘Pain as bad as you can imagine,’ accompanied by the instructions ‘Please rate your pain by indicating the number that best describes your pain on average in the last 24h is recommended as a core outcome measure in clinical trials of chronic pain treatments.’
Self-efficacy
Swedish translation of General Self-Efficacy scale (GSE-10) is used to assess the strength of an individual’s belief in his/her own ability to respond to difficult situations and to deal with setbacks (31).
Diet assessment
During the activity measurement week, the participants will keep a food diary of everything they eat and drink (excl. water) during three consecutive days (including one weekend day; Saturday or Sunday). The results are compiled using a program for nutritional calculations (Dietist Net Pro).
Plans to promote participant retention and complete follow-up {18b}
Participants are provided with a study calendar as a reminder of upcoming appointments and follow-up phone calls to promote participant retention and completion.
Data management {19}
Study data will be collected and managed using REDCap electronic data capture tools hosted at Umeå University. REDCap is a secure, web-based software platform designed to support data capture for research studies. REDCap provides:1) an intuitive interface for validated data capture; 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages; and 4) procedures for data integration and interoperability with external sources (36,37).
REDCap uses Electronical Case Report Forms (eCRF) which increases the compliance to the study protocol used by diabetes specialist nurse. REDCap directly notifies if any data is missing. The program allows secure file uploading of activPAL data as well as records/diaries.
Scheduling function in eCRF makes it possible to schedule the telephone follow-up and if data is lacking i.e. when it is time to make a follow-up telephone call and if participant is receiving the SMS text messages as planned.
Confidentiality {27}
REDCap software ensures the secure data collection and maintenance both during and after the trial.
Plans for collection, laboratory evaluation and storage of biological specimens for genetic or molecular analysis in this trial/future use {33}
Not applicable.
Statistical methods
Statistical methods for primary and secondary outcomes {20a}
Random effects mixed model analysis will be used to determine changes within groups and between the two study arms. The threshold for statistical significance will be set at p <0.05. To avoid overestimating the impact of the intervention, an intention-to-treat approach will be adopted to evaluate the impact on the primary and secondary outcomes.
Interim analyses {21b}
Not applicable.
Methods for additional analyses (e.g. subgroup analyses) {20b}
Self-efficacy is considered a potential moderator for behavioural interventions (38). Therefore, analyses will be stratified based on self-efficacy level in a subgroup analysis.
Methods in analysis to handle protocol non-adherence and any statistical methods to handle missing data {20c}
Random effects mixed model analysis will be used to handle data missing at random for any of the two follow-ups.
Plans to give access to the full protocol, participant level-data and statistical code {31c}
There are no plans for granting public access to the full protocol, participant level-data and statistical code.
Oversight and monitoring
Composition of the coordinating centre and trial steering committee {5d}
The coordinating centre consists of the principal coordinating investigator (PW) and a PhD student (MBS) who support in the coordination of the project. The trial steering committee consists of the regional coordinating investigators (MH, SJ, MN, KR and AU-M) and is -led by the principal coordinating investigator.
Composition of the data monitoring committee, its role and reporting structure {21a}
Research coordinators at the clinical research centre at Umeå University/Region Västerbotten and the principal coordinating investigator will regularly monitor data that is entered in REDCap. The clinical research centre is independent from the sponsor and has no competing interests.
Adverse event reporting and harms {22}
The regional coordinating investigator will be notified by study personnel in case of an adverse event. All adverse events will be reported in REDCap.
Frequency and plans for auditing trial conduct {23}
Not applicable. There is no on-site auditing of the trial.
Plans for communicating important protocol amendments to relevant parties (e.g. trial participants, ethical committees) {25}
The trial steering committee will communicate substantial protocol modifications (when applicable) to relevant parties (referral Ethics Committee, trial participants and study personnel).
Dissemination plans {31a}
Results of the trial will be published in international peer-reviewed scientific journals. There is no obligation for communicating the results to individual patients.