Integrazione di Micronutrienti Multipli con Stratificazione Digitale tra gli Adolescenti in Tanzania (MMSDigitalTZ)

Adolescence (10-19 years) is a critical period of rapid growth and development, second only to the first 1,000 days of life. In low- and middle-income countries, including Tanzania, adolescents experience a double burden of malnutrition, with anemia and other micronutrient deficiencies co-existing alongside rising rates of overweight and obesity. Iron deficiency and poor dietary diversity are major drivers of anemia and are associated with impaired cognitive function, reduced physical capacity, poorer school performance, and compromised future reproductive health. Adolescent girls are at particularly high risk because of increased iron requirements related to growth and menstruation, often in the context of poverty, food insecurity, and constrained access to health services.

At the same time, access to mobile phones and digital technologies is expanding in sub-Saharan Africa, though important inequities remain by geography, gender, and socioeconomic status. Digital health and nutrition strategies (e.g., SMS reminders, mobile messaging, social media content) have shown promise in improving knowledge, some health behaviors, and adherence to supplementation. However, most evidence comes from high-income settings, and few interventions have been designed for or rigorously evaluated among adolescents in low-resource African contexts. Existing programs often emphasize information provision rather than sustained behavior change and rarely address structural barriers to digital access or gender-related inequities. There is limited evidence on how to design and implement digital strategies that effectively complement micronutrient supplementation for adolescents in sub-Saharan Africa.

This trial builds on work by the Africa Research, Implementation Science and Education (ARISE) Network and the ARISE-NUTRINT initiative, which have documented high levels of adolescent anemia and malnutrition in sub-Saharan Africa and explored how adolescents engage with digital technologies for health. Prior mixed-methods research in Tanzania has shown that adolescents are interested in digital nutrition content but face barriers such as limited or shared device access, school policies restricting phone use, and the cost and quality of internet connectivity. The present study is designed to test whether "digitally layered" nutrition education strategies, added to a standard package of multiple micronutrient supplementation (MMS), can reduce anemia and improve nutrition-related behaviors among adolescents.

The ClinicalTrials.gov registration pertains to the main randomized controlled trial. The intervention package was informed by preceding co-design and prototyping phases involving adolescents and key stakeholders (parents, teachers, school administrators, government representatives, civil society, software engineers, and content developers). Using a human-centered design approach, these preparatory phases identified adolescents' needs, preferences, and barriers related to nutrition, anemia, and digital access, and were used to develop and refine prototypes of SMS/WhatsApp messages, in-person digital sessions, and youth-created digital content. Only the finalized intervention components emerging from these phases are evaluated in the main trial.

The main study is a three-arm, individually randomized, non-blinded controlled trial conducted within the Dar es Salaam Health and Demographic Surveillance System (HDSS) area in Tanzania. A total of 1,200 adolescents (approximately equal numbers of boys and girls) aged 15-19 years with access to at least one mobile phone (own or shared) will be enrolled. Participants are randomized in a 1:1:1 ratio, stratified by gender, to: (1) Control; (2) Intervention Arm I (digital Strategy I); or (3) Intervention Arm II (digital Strategy I plus digital Strategy II). Each participant is followed for approximately 9 months, with data collection at baseline, midline (4 months), and endline (9 months).

All three arms receive a core package consisting of in-person nutrition education and MMS. The in-person session is a brief, structured, face-to-face encounter at baseline delivered by trained study staff. It covers adolescent growth and nutrition, causes and consequences of anemia, the role of MMS in preventing micronutrient deficiencies, practical guidance on iron-rich foods and balanced diets, and information on where and how to obtain MMS refills and report side effects. Participants also receive printed brochures tailored to adolescents, addressing healthy diets and dietary diversity, iron-rich foods and enhancers/inhibitors of iron absorption, recognition and prevention of anemia, correct use of MMS, and appropriate health service use. At baseline, all participants receive a 2-month supply of MMS tablets and are instructed to obtain refills approximately every 2 months at designated health facilities. Local health personnel and/or peer support workers assist with MMS distribution and refills.

Digital Strategy I (Intervention Arm I and Intervention Arm II) consists of low-intensity, one-way mobile messaging (SMS and/or WhatsApp). Once per week, participants receive short, age-appropriate messages to the phone number(s) provided at enrollment (own or shared household device). Messages reinforce key nutrition and anemia content from the core session and brochures, prompt daily MMS use and on-time refills, and encourage healthy dietary and physical activity behaviors. Content is designed for low-bandwidth settings and is adapted to be relevant for boys and girls, including material specific to menstruation and iron needs for girls, while maintaining a consistent set of core messages across participants.

Digital Strategy II (Intervention Arm II only) is a higher-intensity engagement package delivered in addition to the core package and Strategy I. It includes regular in-person digital nutrition education sessions (approximately every two weeks) held in school computer labs or community venues and facilitated by trained teacher assistants or peer support workers. These sessions use a simple digital platform (e.g., app or offline interface) incorporating short audio-visual lessons, animations, infographics, interactive quizzes and games, and guided problem-solving activities. Adolescents also work individually or in small groups to create digital content (e.g., short videos, infographics, posters, and brief peer-tailored messages about nutrition and anemia). Youth-created materials can be shared within peer networks via direct phone transfer (e.g., Bluetooth, SD cards) and, where feasible and acceptable, via local social media or messaging platforms. This component is intended to promote active engagement, peer-to-peer diffusion of accurate information, and greater ownership and motivation. Some unintentional exposure to such content among adolescents in the control or Intervention Arm I groups may occur through natural social networks; this is documented through follow-up assessments of exposure to digital nutrition content.

The primary outcome is anemia prevalence at 9 months, defined using WHO age- and sex-specific hemoglobin thresholds, with hemoglobin assessed via finger-prick capillary samples at baseline, 4 months, and 9 months. Key secondary outcomes include severity of anemia, hemoglobin concentrations, adherence to MMS (consumption and refills), nutrition literacy, dietary behaviors (including fruit and vegetable intake and dietary diversity), physical activity, anthropometric indicators (including BMI categories), and indicators of digital literacy, access, and engagement. Process outcomes (e.g., reach and fidelity of digital delivery, message delivery and recall, attendance at digital sessions, and exposure to youth-created materials) and economic outcomes (costs and cost-effectiveness of the digital layering strategies) will also be assessed. Outcomes will be examined overall and stratified by gender to assess potential differential effects among boys and girls.

Quantitative analyses will follow an intention-to-treat principle, including all randomized participants in their assigned arms regardless of intervention exposure level. The primary comparison will estimate the effect of Intervention Arms I and II versus the Control arm on anemia prevalence at 9 months, with models accounting for repeated measures and pre-specified covariates. Secondary analyses will examine impacts on other hematologic, behavioral, anthropometric, and digital outcomes and will formally assess effect modification by gender. Complementary qualitative data from focus group discussions with adolescents and interviews with intervention delivery personnel and stakeholders will be analyzed thematically to explore acceptability, feasibility, fidelity, perceived benefits and harms, and contextual factors influencing implementation. Cost and cost-effectiveness analyses will use trial data combined with additional epidemiologic and costing information to estimate the incremental cost per anemia case averted and to inform scalability.

The trial is considered minimal risk. Potential risks relate primarily to minor discomfort from finger-prick blood collection, possible mild side effects from MMS, and privacy or confidentiality concerns related to data collection and group discussions. Standard procedures for informed consent/assent, secure data handling, and referral to health services are in place. A data and safety monitoring plan governs the reporting and review of adverse events and any unanticipated problems. Overall, the study is designed to generate rigorous evidence on whether layering appropriately designed digital interventions onto MMS supplementation is a feasible, acceptable, and cost-effective strategy to reduce anemia and improve broader nutrition and health behaviors among adolescents in Tanzania, with implications for similar low- and middle-income settings.