A complex behavioural change intervention to reduce the risk of diabetes and prediabetes in the pre-conception period in Malaysia: Study protocol for a randomised controlled trial

Background: Over the past two decades, the population of Malaysia has grown rapidly and the prevalence of diabetes mellitus in Malaysia has dramatically increased, along with the frequency of obesity, hyperlipidaemia and hypertension. Early-life influences play an important role in the development of non-communicable diseases. Indeed, maternal lifestyle and conditions such as gestational diabetes mellitus or obesity can affect the risk of diabetes in the next generation. Lifestyle changes can help to prevent the development of type 2 diabetes mellitus. This is a protocol for an unblinded, community-based, randomised controlled trial in two arms to evaluate the efficacy of a complex behavioural change intervention, combining motivational interviewing provided by a community health promoter and access to a habit formation mobile application, among young Malaysian women and their spouses prior to pregnancy. Method/design: Eligible subjects will be Malaysian women in the age group 20 to 39years, who are nulliparous, not diagnosed with diabetes and own a smartphone. With an alpha-value of 0.05, a statistical power of 90%, 264 subjects will need to complete the study. Subjects with their spouses will be randomised to either the intervention or the control arm for an 8-month period. The primary endpoint is change in waist circumference from baseline to end of intervention period and secondary endpoints are changes in anthropometric parameters, biochemical parameters, change in health literacy level, dietary habits, physical activity and stress level. Primary endpoint and the continuous secondary endpoints will be analysed in a linear regression model, whereas secondary endpoints on an ordinal scale will be analysed by using the chi-squared test. A multivariate linear model for the primary endpoint will be undertaken to account for potential confounders. This study has been approved by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14-904-21963) on 21 September 2015. Discussion: This study protocol describes the first community-based randomised controlled trial, to examine the efficacy of a complex intervention in improving the pre-pregnancy health of young Malaysian women and their spouses. Results from this trial will contribute to improve policy and practices regarding complex behavioural change interventions to prevent diabetes in the pre-conception period in Malaysia and other low- and middle-income country settings. Trial registration: This trial is registered with ClinicalTrials.gov (www.clinicaltrials.gov) on 30 November 2015, Identifier: NCT02617693. The primary objective of the trial is to evaluate the efficacy of a complex behavioural change intervention combining behaviour change counselling provided by community health promoters (CHPs) and utilisation of an E-health platform to enhance women’s health prior to pregnancy. This will be measured through the change in waist circumference after the 8-month intervention period between female subjects exposed to the intervention and female subjects exposed to standard of care in a control group. The secondary objectives are to evaluate the efficacy of the intervention on health literacy, dietary habits, physical activity, sedentary behaviour and stress level. The trial is designed as an unblinded, RCT to assess the efficacy of a complex behavioural change intervention aiming to improve the overall health of young women prior to their first pregnancy. The intervention follow-up period is 8 months from randomisation/baseline. After end trial the subjects will be monitored for a period of 12 months for pregnancy. Figure 1 gives the flow diagram of the trial. The trial was designed following the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement (see Additional file 1). The flow diagram of the Jom Mama trial The trial will be carried out in the district of Seremban in the state of Negeri Sembilan, Malaysia. This location was selected due to Negeri Sembilan having a higher prevalence of diabetes (22.0 %) compared to the national prevalence (15.2 %) [22]. Ethnic diversity is one of the key features of Malaysia and the district of Seremban has a representation of the three major ethnic groups: Malay, Chinese and Indian, 67.4, 24.6 and 7.3 %, respectively [23]. The target subjects will be newly registered married or engaged women. The woman will be recruited with her spouse, who also will be exposed to the intervention. Eligible subjects must meet all the following inclusion criteria: Subjects meeting any of the following criteria will be excluded from participation in the trial: Newly married or engaged women and their spouses will be recruited from 2 November 2015, primarily from five designated primary health clinics in the district of Seremban, whereas Muslim Malay couples are obligated to conduct a pre-marriage screening, which involves a HIV/AIDS test. Other sites in Seremban such as the state marriage registration office, temples and churches or other sites (work places, malls, gyms, etc.) will also be approached for recruitment purposes. A research officer will meet the young couples face-to-face and provide an explanation of the study rationale and a description of the Jom Mama project. The women and spouse will be given an opportunity to ask questions and those who are interested in the study will have their contact details recorded for further contact and arrangements for a baseline visit. If possible, the couple will be given a clinic appointment for baseline measurements at one of the five designated primary health clinics in Seremban. If the couple need time to consider their involvement, the research officer will follow-up with three phone calls over the next 3 weeks. If, at these phone calls the couple accepts participation in the trial, a baseline appointment will be made. If the couple does not answer the three phone calls or rejects the offer to participate, they will be dropped from the participation registration list. The intervention has two components. The first component is an interaction with a CHP who will be in contact with the women and their spouses during the 8-month intervention period. These contacts will be a combination of three face-to-face meetings, three phone calls and communication through Whatsapp group chat. The CHP will use motivational counselling techniques, i.e. motivational interviewing, to support and motivate the young women and their spouses to live a healthier lifestyle. The second component is an E-health platform which consists of two elements: (1) a mobile application in the form of a habit formation application, where subjects and spouses can select different challenges for obtaining a healthy diet, more physical activity and less sedentary behaviour during the intervention period; and (2) a web-based back-end interface which can be accessed by the CHP, which will be her tool to assess the women and their spouses’ lifestyle situation. The CHP uses a dashboard to follow the progress of subject and spouse in performing the challenges, and uses the information to interact with the subject and her spouse during the contact points in the intervention. Figure 2 presents screen shots of the web-based application the CHPs are using. The CHP will function as a personal coach to engage, support and guide the young woman and her spouse toward achieving and maintaining a healthier lifestyle. During the interaction over the intervention period of 8 months, the CHPs will assess the subject and her spouse’s health risks and behaviour, share information on healthy living and support the subjects and spouses to reach their personal health goals. The objectives of each contact point are presented in Table 1. Screen shot from the web application, showing the couples’ dashboard. Screen shot a Shows the overview of all couples under one community health promoter (CHP). The traffic lights give an indication on how active the couple are in performing their selected challenges. The second column indicates when the couple was last active on the mobile application. The last column informs when the CHP has the next appointment with the couple. Screen shot b Shows the progress over time for one couple. The graphic can shift between wife and husband and, in this example, it is only showing the wife. The upper columns indicate how many times the challenges have been performed per month. The lower columns indicate how many times each challenge has been performed Overview of the objective of each face-to-face and phone call contact point The CHP role will be carried out by community nurses who are currently working in primary health care in Malaysia. Prior to the start of the intervention, the community nurses undertook training in becoming a CHP. This was a 5-day training programme with sessions in motivational interviewing techniques, the use of the E-health platform and basic knowledge of healthy diet and physical activity. The training was carried out by local trainers who are social-psychologists with expertise in motivational interviewing techniques, professional dieticians and physical activity experts. During the trial, refreshment training with the social-psychologist trainers will take place to support and help the CHPs in addressing challenging situations they encountered with the young women and their spouses. The mobile application is a habit-formation application, which incorporates personal goal setting, progress tracking and general information on healthy lifestyles. The mobile application has two key components comprising diet and physical activity. Under each domain several challenges have been developed which can be selected by the subject on a monthly basis in dialogue with the CHP. The application will suggest several challenges for healthy eating, such as making healthy food choices and healthy food preparation, and interactive options for the subject to stay active and prevent sedentary behaviour. In addition, the mobile application will also provide information on what constitutes a healthy lifestyle and further information on how to stay healthy before pregnancy. The mobile application is available on iOS and Android operating systems. Figure 3 presents several screen shots from the mobile application. Screen shots of mobile application. a The main screen, showing the couple’s process for the particular month. The icons on top illustrate the categories of the different challenges selected (two physical activity challenges and one healthy eating challenge). In the middle, is the progress bar, showing the progress of the user and her spouse for this particular month. Lowest, are the selected challenges listed and how many times they should be performed in one week. b By tapping on the challenges, a description of the different challenge is showing (example of the healthy eating challenge). c When the challenge has been performed, the subject will ‘check-in’, and by doing that be awarded 2 points for performing the challenges. d A timer can be set for each challenge, so a reminder will be send to the subject on the given time to perform the challenge. e The subject is selecting the challenge out of a list set challenges. f The Flash challenge is a bonus challenge, which the subject can select when it becomes available. This occurs randomly during the intervention period. The Flash challenge will give extra points Subjects in the control arm will receive standard of care, which is no contact with a CHP and no access to the E-health platform. They will receive one phone call from a research officer towards the end of the intervention period to remind them of their endpoint visit. Change in waist circumference was selected as the primary endpoint because of its validity as a superior measurement for assessing abdominal fat content and associated obesity health risk, as compared to a measure such as body mass index (BMI) [24–26]. In addition, there are existing national Malaysian data on population waist circumference, which allow for the study results to be comparable on a national level. In the present trial, the primary endpoint is predicted to provide a 2-cm reduction of waist circumference in the intervention group compared to the control group, which will reflect a reduction of central fat distribution. The reduction of 2 cm in waist circumference as a primary endpoint is based on the mean from a number of studies indicating that a decrement of waist circumference is possible with a lifestyle changing intervention over a period of 8 months [27–31]. The variation between the two time-points in these studies was small (standard deviation (SD) of 3–5) after the intervention period, and we therefore assume an expected within-person estimate of SD = 5. The secondary endpoint will be as follows: The incidence of GDM, confirmed by an oral glucose tolerance test (OGTT), will be assessed in the subjects who will complete the intervention period and who become pregnant in the post-trial monitoring period. The OGTT will be taken at weeks 26–28 of the pregnancy. Data will be captured retrospectively and obtained from medical charts. Anthropometric measurements, blood pressure and data on physical activity, dietary, stress and health literacy will be collected from the subject’s spouse. Socio-demographic data and family medical history will be collected from both the subject and the spouse. These variables are collected to adjust for confounding effects. The sample size calculation is based on a 2-cm reduction in waist circumference, in the primary endpoint of waist circumference between the intervention and control arms at 8 months. Assuming a 5 % level of significance (alpha = 0.05), a statistical power of 90 % (beta = 0.10) and a SD of 5 cm using a two-sided t test, 132 women per arm are required. Taking into consideration a 20 % drop-out rate, and that 20 % will be pregnant, a total of 660 women would be randomised/enrolled to ensure 264 subjects to cover both the intervention and control arms. At the baseline measurement visit, subjects will be randomised into the intervention and control arms at a 1:1 allocation ratio. Random allocation sequences will be computer- generated with block sizes of six subjects. Each clinic will be provided with a sufficient number of identification (ID) numbers with randomisation codes. When a subject is enrolled in the trial, the study nurse should assign the lowest available ID number to the subject from the list of ID numbers. The Institute for Health System Research (IHSR) under the MoH has prepared the randomisation list and these are distributed to the five designated primary health clinics in Seremban. A copy is maintained by the IHSR. Study nurses will be trained to conduct the data collection at the five designated primary health clinics in Seremban district. At the baseline assessment, the principles of the trial will be explained again for the subject and spouse and they will be asked to provide consent by signing the consent form. One original copy of each form will be kept by the study nurse who will file the document on site. One copy of each form will be given to the subjects. The women and their spouses will have linked ID numbers by assigning each subject and spouse the same ID number with subject ID ending with the number ‘2’ and spouse ID ending with the number ‘1’ respectively. At baseline the subjects will undergo measurements of waist circumference, hip circumference, weight, height and blood pressure by following standardised procedures based on World Health Organisation (WHO) STEPS surveillance [32]. Only the subject in the couple will provide a 10-mL blood sample to measure glycated haemoglobin A1c (HbA1c) and a fasting lipid profile (triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC)). Due to the need for a fasting lipid profile analysis, the subject will be asked to come to the clinic after fasting for a minimum of 9 h. In line with this, the data collection time-points are planned to be in the morning. The European Health Literacy Tool Q-47 (HL-EU-Q47) [33] (HL-EU Consortium 2012), the Malaysian Food Frequency Questionnaire (FFQ), modified to be used in the current trial [2]; the International Physical Activity Questionnaire (IPAQ) [2]; and the Depression Anxiety Stress Scale 21-items (DASS-21) [34, 35] will be used to collect data on level of health literacy, dietary pattern, physical activity level, and stress level, respectively. Data such as socio-demographic parameters and family history of diabetes will be collected by structured interviews with the study nurse. The spouse will undergo the same data measurements, with the exception of blood sampling. At the end of the data collection, and before subject and spouse leave, data will be checked by the study nurse and site coordinator or research officer, to ensure that all data forms and questionnaires have been filled correctly. When data collection is completed the data collection forms and questionnaires will be signed-off by the study nurse and site coordinator or research officer. At the end of the baseline visit, if the subject is randomised to the intervention, the first contact with a CHP will be made. The subject and spouse will be introduced to the mobile application and it will be installed on the subject’s and spouse’s smartphone device. If the subject and spouse have sufficient time the CHP will proceed with the first contact point. If the subject and spouse do not have the time, an appointment will be set in the next 5 days either at the clinic or at the couple’s house. The same measurements, except height, socio-demographic parameters and medical history, described above will be conducted at the endpoint visit (Table 2). Data collection at each time-point in the Jom Mama trial Data collection on woman;● Data collection on spouse; a FFQ Food Frequency Questionnaire, b IPAQ International Physical Activity Questionnaire, c DASS-21 Depression Anxiety and Stress Scale 21-items, d Fasting lipid profile: will be measured as a combination of: total cholesterol (TC) level, low-density lipoprotein cholesterol (LDL-C) level, high-density lipoprotein cholesterol (HDL-C) level and triglyceride (TG) level; 5Exit point visit will occur if the woman becomes pregnant between 4.1 months and 8 months after randomisation If a subject becomes pregnant within the 8-month intervention period, she will be withdrawn from the trial. Exit measurements, which are similar to those at the endpoint visit, will be performed only for subjects who become pregnant between 4.1 and 8 months from baseline. For those who become pregnant between baseline and month 4 in the intervention period, no measurements will be taken. All data will be managed and stored with protection of data privacy. Documentation as well as corrections, if necessary, will be done in accordance to Good Clinical Practice guidelines. All protocol-required information collected during the trial must be entered on a data collection form containing the four questionnaires. The original completed data collection form will be send to IHSR, MoH Malaysia, where double data entry will be performed by two independent data clerks. The completeness, validity and plausibility of data are examined by validating programmes, which thereby generate queries. The generated queries will be checked with original data collection forms and all changes from the original data are documented on audit files. Data will be maintained and analysed in the statistical Stata programme, version 12.0 or higher (StataCorp LP). Monitoring will be performed regularly by an independent clinical research organisation from Malaysia to check the completeness of the contents of records and the data collection forms, the adherence to the protocol and the progress of enrolment. The null hypothesis is that there is no difference in the change in waist circumference between the intervention and the control group after the 8-month intervention. The alternative hypothesis is that the decrement in waist circumference will be bigger in the intervention group compared to the control group after the 8-month intervention. A linear regression model will be used to assess the difference in the change of waist circumference from baseline to end of intervention, with the difference in waist circumference as the independent variable, treatment (intervention versus control) and baseline waist circumference as covariates. Additional tests will be performed for the impact of the intervention in both high- (waist circumference above 80 cm) and low-risk (waist circumference below 80 cm) groups. This will be done by subgroup analysis or by assessing the proportional changes in the primary endpoint. Each subgroup will also be analysed in a linear regression model. The continuous secondary endpoints will be analysed in a linear regression model, whereas the difference in the change of each secondary endpoint from baseline to end of intervention, will be the dependent variable, treatment (intervention versus control) and baseline value as covariate. Regarding health literacy (HL-EU-Q47), physical activity (IPAQ) and stress (DASS-21) all the variables are ordinal and, therefore, independence between intervention and control groups will be tested with the chi-squared test. Change in nutrient intakes will be compared between the groups using a generalised linear model, with additional adjustments for total energy intake. Nutrient and food patterns before and after the intervention will be explored in both groups separately by using dimension reduction techniques such as principal component analysis. Multivariate analysis will be performed to assess the association between exposure to the intervention, primary endpoints and secondary endpoints (BMI, waist-to-height and waist-to-hip ratio, HbA1c, lipid profile, blood pressure, health literacy, physical activity, dietary intake and stress level) using linear regressions. In this model the secondary endpoint will be included in the model as covariates and the estimated coefficients will be presented unadjusted and adjusted for appropriate and/or effect modifier and/or confounders. Furthermore, interactions between the secondary endpoints will also be explored. Several supportive analyses will be performed. The first supportive analysis will explore the relation between subjects’ and spouses’ change in waist circumference and other anthropometric measurements, diet, physical activity, health literacy and stress. A second supportive analysis will explore whether a short intervention period (subjects who become pregnant between 4.1 and 8 months in the intervention period), will also have an impact on the primary endpoint and secondary endpoints. A time variable explaining how long they have been included in the intervention will be included in the models as a covariate. At the end of the 12-month post-intervention monitoring period, a full analysis will be conducted on subjects who become pregnant within 12 months after completing the intervention. This will be done by assessing the incidences of GDM among women who became pregnant between treatment groups, using a chi-squared test. Additionally, a logistic regression model to explore associations between the number of subjects with GDM and several secondary endpoints will be conducted. The study protocol version 4.0 dated 12 August 2015 has received ethical and governance approvals by the Medical Research and Ethics Committee of the Ministry of Health Malaysia (protocol number: NMRR-14-904-21963) on 21 September 2015. The study is performed in compliance with the Declaration of Helsinki. Written informed consent will be taken from each participant prior to study enrolment by trained study nurse. The trial was registered at ClinicalTrials.gov, Identifier: {“type”:”clinical-trial”,”attrs”:{“text”:”NCT02617693″,”term_id”:”NCT02617693″}}NCT02617693 on 30 November 2015. In the event of an abnormal laboratory test results for Hb1Ac or a newly suspected or diagnosed health concern during a subject’s measurements (i.e. high blood pressure or a high score in the DASS-21 tool) at baseline/exit point/endpoint, the subject will be referred to their primary health care physician for further examination.