SHINE Sanitation, Hygiene, Infant Nutrition Efficacy Project

Sponsor

Johns Hopkins Bloomberg School of Public Health (Other)

Overall Status

Completed

CT.gov ID

NCT01824940

Collaborator

Ministry of Health and Child Welfare, Zimbabwe (Other), Zvitambo (Other), Cornell University (Other), University of London (Other), Bill and Melinda Gates Foundation (Other), Department for International Development, United Kingdom (Other), Wellcome Trust (Other), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

5,280

Enrollment

Location

Arms

56.9

Duration (Months)

92.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Globally, stunting affects 26% (165 million) of under-5-year children, underlies 15-17% of their mortality and leads to long-term cognitive deficits, fewer years and poorer performance in school, lower adult economic productivity, and a higher risk that their own children will also be stunted, perpetuating the problem into future generations. Stunting begins antenatally and peaks at 18-24 months of postnatal life, when mean length-for-age Z-score (LAZ) is about -2.0 among children living in Africa and Asia. Improving the diets of young children can reduce stunting, though, at best, only by about one-third. Frequent diarrheal illness has also been implicated. However, the effect of diarrhea on permanent stunting is relatively small, maybe because children grow at "catch-up" rates between illness episodes.

The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial is motivated by a 2-part premise:

A major cause of child stunting and anemia is Environmental Enteric Dysfunction (EED). EED is a subclinical disorder of the small intestine, which is virtually ubiquitous among asymptomatic people living in low-income settings throughout the world. EED is characterized by increased permeability which facilitates microbial translocation into the systemic circulation and triggers chronic immune activation.
The primary cause of EED is infant ingestion of fecal microbes due to living in conditions of poor quality and quantity of water, sanitation, and hygiene (WASH).

Condition or Disease	Intervention/Treatment	Phase
Growth; Stunting, Nutritional Anemia	Behavioral: Standard care Other: WASH Dietary Supplement: Infant and young child feeding Other: WASH and Nutrition	N/A

Detailed Description

The Sanitation Hygiene Infant Nutrition Efficacy ("SHINE") trial will test the effects of two packages of interventions: 1) improved water, sanitation and hygiene (WASH) and 2) improved infant and young child feeding (IYCF) on child stunting and anemia in the first 18 months of life. The trial will be conducted in rural Zimbabwe where WASH is poor, food insecurity high, and where about 15% of pregnant women are infected with HIV. The study will enroll 5282 women early in pregnancy and follow them and their infants until 18 months after delivery. The study will be a cluster-randomized controlled trial: two entire districts in central Zimbabwe have been divided into 212 geographic areas, each of about 100 households. The areas will be randomly allocated (that is, assigned by according to chance like the flip of a coin) to one of four interventions:

Improved WASH (a ventilated pit latrine, hand washing facilities with soap, drinking water treatment, a protected play space and health lessons to adopt improved hygiene behaviors)
Improved Infant Nutrition (health lessons on best infant feeding practices and a nutritional supplement (Nutributter) to be fed daily to babies from 6 to 18 months).
Improved WASH and Infant Nutrition (both interventions)
Standard of Care

All women living in the two districts who become pregnant during the recruitment period of the study will be invited to enroll. They will receive one of the 4 packages of interventions according to the area where they live. Health lessons will be given by Village Health Workers. Latrines and hand washing facilities will be constructed by building teams. Mothers will be followed up by research nurses at 7 months gestation, and at 1, 3, 6, 12, and 18 months after delivery. Primary outcomes are infant height and hemoglobin at 18 months of age.

Within SHINE we will measure two causal pathways: the biomedical pathway and the program impact pathway.

The biomedical pathway comprises the infant biologic responses to the WASH and IYCF interventions that ultimately result in attained stature and hemoglobin concentration at 18 months of age; it will be elucidated by measuring biomarkers of intestinal structure and function (inflammation, regeneration, absorption and permeability); microbial translocation; systemic inflammation; and hormonal determinants of growth and anemia among a subgroup of infants enrolled in an EED substudy. The investigators will also ask these mothers to record daily any episodes of diarrhea; blood/mucus in the stool; cough; fast or difficult breathing; fever; and lethargy preventing breastfeeding, that the child has between 1 month and 18 months of age. A subgroup of infants will also have stool samples collected during diarrhoeal episodes to evaluate reductions in pathogen-specific diarrhoea following WASH interventions.

Since the mothers enrolled in SHINE will have lived in unsanitary living conditions throughout their lives, it is anticipated that most will have some degree of EED themselves. It is hypothesized that resulting chronic inflammation contributes to adverse birth outcomes, such as prematurity and low birth weight. This question will be investigated through an observational design. For all mothers enrolled in SHINE, the sugar absorption test described above will be conducted and specimens of saliva, stool and blood collected and archived at the 10-12 week gestation visit for subsequent assessment of EED biomarkers. The association of severity of EED with risk of adverse birth outcomes (low birth length and weight; miscarriage, stillbirth, and premature delivery) will be assessed.

The program impact pathway comprises the series of processes and behaviors linking implementation of the interventions with the two child health outcomes; it will be modeled using measures of fidelity of intervention delivery and household uptake of promoted behaviors and practices. We will also measure a range of household and individual characteristics, social interactions, and maternal capabilities for childcare, which we hypothesize will explain heterogeneity along these pathways.

Study Design

Study Type:

Interventional

Actual Enrollment :

5280 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

None (Open Label)

Masking Description:

Given the nature of the intervention, masking to treatment group is not possible.

Primary Purpose:

Prevention

Official Title:

Sanitation, Hygiene, Infant Nutrition Efficacy Project

Study Start Date :

Nov 1, 2012

Actual Primary Completion Date :

Jul 1, 2017

Actual Study Completion Date :

Jul 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Standard of Care The Standard of Care interventions are the blanket interventions.	Behavioral: Standard care Standard Care: Exclusive breastfeeding promotion for all infants, birth to 6 months Strengthened PMTCT (prevention of mother to child transmission of HIV) services Strengthened Village Health Worker system
Active Comparator: WASH One of two active interventions to be studied in this 2X2 (two by two) Factorial trial: Intervention 1: a package of interventions to improve household sanitation and hygiene (WASH)	Other: WASH WASH: Standard care interventions Provide household ventilated pit latrine, water treatment solution, and monthly liquid soap, two hand-washing facilities and protected infant play space Provide interpersonal communication interventions promoting feces disposal in a latrine, HWWS (hand washing with soap), drinking water treatment, hygienic weaning food preparation, and preventing babies from putting dirt and animal feces in their mouths.
Active Comparator: Nutrition One of two active interventions to be studied in this 2X2 Factorial trial: Intervention 2: a package of interventions to improve infant and young child feeding (IYCF)	Dietary Supplement: Infant and young child feeding IYCF: Standard care interventions Provide 20 g/d Nutributter from 6-18 months Provide interpersonal communication interventions promoting optimal use of locally available foods for complementary feeding after 6 months, continued breastfeeding and feeding during illness. Other Names: Nutrition
Active Comparator: WASH and Nutrition This arm receives a combination of all standard care interventions, all WASH and all IYCF interventions.	Other: WASH and Nutrition WASH AND IYCF interventions Standard care interventions All WASH interventions All IYCF interventions Other Names: WASH and IYCF

Outcome Measures

Primary Outcome Measures

Infant length at 18 months [18 months of age. Protocol and Statistical Analysis Plan are available at https://osf.io/w93hy.]
Recumbent length measured by length board
Infant hemoglobin at 18 months [18 months]
Measured by Hemocue

Secondary Outcome Measures

Infant environmental enteric dysfunction [1, 3, 6, 12 and 18 months of age]
Assessed in a subgroup of infants recruited to the EED substudy by assessing domains of the hypothesized EED pathway using biomarkers of intestinal structure and function (inflammation, regeneration, absorption and permeability); microbial translocation; systemic inflammation; and hormonal determinants of growth and anemia
Infant weight, mid-upper arm circumference and head circumference [At 18 months, and (with length) at intermediate time-points of 1, 3, 6 and 12 months]
Measured by standardized anthropometry protocols at each age
To describe the Program Impact Pathways (PIP) linking implementation of each randomized intervention (WASH and IYCF) with length and hemoglobin concentrations [Throughout follow-up]
Assessment of quality of VHW training and supervision; VHW Capacity, defined as a composite of attained knowledge, goal setting capacity, and achieved performance; Fidelity of intervention implementation, defined as degree of conformance with protocol specifications for both VHW and mother; Attained maternal knowledge and skills assessed by questionnaire and observation; Uptake or adoption of promoted behaviors by mothers and their households assessed by questionnaire and observation.
Exclusive breastfeeding [First 6 months of life]
To describe the prevalence of exclusive breastfeeding among all infants enrolled in the trial by maternal/infant HIV status.
To evaluate the effect of the IYCF intervention on uptake of improved infant feeding practices by maternal/infant HIV status [6-18 months of age]
Infant diet quality as assessed by World Health Organization IYCF indicators ; infant nutrient intake from complementary foods assessed by 24 hour dietary recall; appropriate use of Nutributter from 6 to 18 months.
To evaluate the effect of the WASH intervention on the 5 key behaviors it promotes by maternal/infant HIV status [Throughout follow-up]
Proper disposal of animal and human feces; Handwashing with soap after fecal contact; Point-of-use chlorination of drinking water; Protecting children from ingestion of dirt and feces; Feeding baby freshly prepared foods, or reheating leftover food.
Relative contributions of diarrhea vs EED [Birth to 18 months]
To model the relative contributions of diarrheal disease and EED in mediating the effects of improved WASH on child length and hemoglobin concentrations, stratified by maternal/infant HIV status.
To measure the strength of association between other potential causes of stunting and anemia (other than poor WASH or IYCF) with linear growth and hemoglobin [Throughout follow-up]
Maternal schistosomiasis infection during pregnancy; Maternal HIV infection together with adherence to antiretroviral and cotrimoxazole regimens during pregnancy and lactation; Infant HIV infection or exposure, together with adherence to antiretroviral and/or cotrimoxazole regimens; Exposure to dietary mycotoxin contamination by the mother during pregnancy and lactation, and by the infant during complementary feeding.
Infant diarrhea prevalence, incidence and severity [1 month to 18 months of age]
Assessed by 7-day morbidity history in all infants, and by daily morbidity diary in a subgroup of infants
Child neurodevelopment [24 months of age]
Assessed by MacArthur-Bates Communication Developmental Inventory; Malawi Development Test (MDAT); A not B task; Delayed inhibition task; and Caregiver Child Interaction assessment in a subgroup of children
Prevalence of mycotoxin exposure among mothers and infants [Maternal samples assessed at baseline; infant samples assessed birth to 18 months]
Detectable AFB1-lysine in plasma and detectable AFM1 in urine; detectable Fumonisin B1 in urine; detectable deoxynivalenol in urine; detectable zearalenone in urine; detectable ochratoxin A in urine; detectable T-2 in urine
MAternal and infant microbiota [Maternal samples from baseline and 1 month postpartum; infant samples birth to 18 months of age]
16S rRNA and whole genome sequencing of DNA and RNA from stool to define th composition and function of the microbial community that inhabits the human intestine.
Infant rotavirus vaccine and polio vaccine immunogenicity [1 and 3 months of age]
Measurement of rotavirus IgA titre in plasma, measurement of polio virus IgA titre in plasma
Adverse birth outcomes: miscarriage, still birth, small for gestational age, preterm delivery, neonatal death [Maternal pregnancy exposures, infant outcomes through 1 month postpartum]
Association of maternal exposures during pregnancy (EED, anemia, mycotoxin exposure, HIV infection, schistosomiasis infection) on each adverse birth outcome
Bioimpedance analysis, skinfold thicknesses and leg length measurement [24 months in a subsample of infants]
Assess the impact of the randomized interventions on infant body composition. analysis plan at https://osf.io/t9zd4
Observational study of WASH and non-WASH infants [About 14 months of age]
90 WASH and 90 non-WASH infants will undergo 6 h structured observation to directly observe and assess intervention impact on hygiene behaviors
Assess metabolic pathways of pathogenesis of stunting [12 month urines; longitudinal stools from 150 mother-infant pairs from 32 week gestation, and 1,3,6,12,and 18 months postpartum]
Urine and stool samples analysed by untargeted metabolomics
Friendship Bench for treatment of depression: a pilot study [August 2018 - January 2019 (about a year after the end of the trial).]
30 SHINE mothers will be recruited to pilot a depression intervention for feasibility and acceptability

Eligibility Criteria

Criteria

Ages Eligible for Study:

15 Years to 49 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Study participants will be women who are rural residents of Chirumanzu or Shurugwi districts in Zimbabwe and who become pregnant during the enrollment period of the trial and are identified and consent to participation during pregnancy, and their live born infants. A total of 5280 women will be enrolled.

Inclusion Criteria:

Pregnant women residing in the study districts, whose pregnancy is confirmed by a urine pregnancy test.

Exclusion Criteria:

Women residing in the study districts who become pregnant during the enrollment period but do not consent to join the trial
Women who reside in urban areas of these two districts
Infants with major non-fatal abnormalities will not be excluded from study procedures, but will be excluded from the final analytic sample if the abnormality is likely to directly affect gut health/function or stature (e.g. neural tube defects, cerebral palsy, Down syndrome)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zvitambo	Harare		Zimbabwe

Sponsors and Collaborators

Johns Hopkins Bloomberg School of Public Health
Ministry of Health and Child Welfare, Zimbabwe
Zvitambo
Cornell University
University of London
Bill and Melinda Gates Foundation
Department for International Development, United Kingdom
Wellcome Trust
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)