Growth; Stunting, NutritionalSHINENCT01824940
SHINE Sanitation, Hygiene, Infant Nutrition Efficacy Project
A study testing WASH, Infant and young child feeding and WASH and Nutrition in people with Growth; Stunting, Nutritional and Anemia, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Zimbabwe.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 to 49 years, women only
- Conditions the study is for
- Growth; Stunting, Nutritional, Anemia
- What is being tested?
- WASH, Infant and young child feeding and WASH and Nutrition
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,280 participants
- Where
- 1 siteZimbabwe
- Study dates
- Nov 2012to 31 Jul 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 49 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Pregnant women residing in the study districts, whose pregnancy is confirmed by a urine pregnancy test.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sanitation, Hygiene, Infant Nutrition Efficacy Project
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).
Read the 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.
- Conditions
- Growth; Stunting, Nutritional, Anemia
- Being tested
- Standard care, WASH, Infant and young child feeding, WASH and Nutrition
- Keywords
- Cluster randomized trial, Nutrition, Water Sanitation Hygiene, Environmental enteropathy
- Medical subject headings
- Growth Disorders, Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard careBehavioural
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
WASHOther
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.
Infant and young child feedingDietary supplement
Also called Nutrition
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.
WASH and NutritionOther
Also called WASH and IYCF
WASH AND IYCF interventions
- Standard care interventions
- All WASH interventions
- All IYCF interventions
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Placebo comparator | The Standard of Care interventions are the blanket interventions. Receives: Behavioral: Standard care |
| WASH | Active comparator | 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) Receives: Other: WASH |
| Nutrition | Active comparator | 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) Receives: Dietary Supplement: Infant and young child feeding |
| WASH and Nutrition | Active comparator | This arm receives a combination of all standard care interventions, all WASH and all IYCF interventions. Receives: Other: WASH and Nutrition |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infant length at 18 months
Recumbent length measured by length board
Measured: 18 months of age. Protocol and Statistical Analysis Plan are available at https://osf.io/w93hy.
Infant hemoglobin at 18 months
Measured by Hemocue
Measured: 18 months
Secondary outcomes (18)
Infant environmental enteric dysfunction
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
Measured: 1, 3, 6, 12 and 18 months of age
Infant weight, mid-upper arm circumference and head circumference
Measured by standardized anthropometry protocols at each age
Measured: At 18 months, and (with length) at intermediate time-points of 1, 3, 6 and 12 months
To describe the Program Impact Pathways (PIP) linking implementation of each randomized intervention (WASH and IYCF) with length and hemoglobin concentrations
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.
Measured: Throughout follow-up
Exclusive breastfeeding
To describe the prevalence of exclusive breastfeeding among all infants enrolled in the trial by maternal/infant HIV status.
Measured: First 6 months of life
To evaluate the effect of the IYCF intervention on uptake of improved infant feeding practices by maternal/infant HIV status
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.
Measured: 6-18 months of age
To evaluate the effect of the WASH intervention on the 5 key behaviors it promotes by maternal/infant HIV status
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.
Measured: Throughout follow-up
Relative contributions of diarrhea vs EED
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.
Measured: Birth to 18 months
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
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.
Measured: Throughout follow-up
Infant diarrhea prevalence, incidence and severity
Assessed by 7-day morbidity history in all infants, and by daily morbidity diary in a subgroup of infants
Measured: 1 month to 18 months of age
Child neurodevelopment
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
Measured: 24 months of age
Prevalence of mycotoxin exposure among mothers and infants
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
Measured: Maternal samples assessed at baseline; infant samples assessed birth to 18 months
MAternal and infant microbiota
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.
Measured: Maternal samples from baseline and 1 month postpartum; infant samples birth to 18 months of age
Infant rotavirus vaccine and polio vaccine immunogenicity
Measurement of rotavirus IgA titre in plasma, measurement of polio virus IgA titre in plasma
Measured: 1 and 3 months of age
Adverse birth outcomes: miscarriage, still birth, small for gestational age, preterm delivery, neonatal death
Association of maternal exposures during pregnancy (EED, anemia, mycotoxin exposure, HIV infection, schistosomiasis infection) on each adverse birth outcome
Measured: Maternal pregnancy exposures, infant outcomes through 1 month postpartum
Bioimpedance analysis, skinfold thicknesses and leg length measurement
Assess the impact of the randomized interventions on infant body composition. analysis plan at https://osf.io/t9zd4
Measured: 24 months in a subsample of infants
Observational study of WASH and non-WASH infants
90 WASH and 90 non-WASH infants will undergo 6 h structured observation to directly observe and assess intervention impact on hygiene behaviors
Measured: About 14 months of age
Assess metabolic pathways of pathogenesis of stunting
Urine and stool samples analysed by untargeted metabolomics
Measured: 12 month urines; longitudinal stools from 150 mother-infant pairs from 32 week gestation, and 1,3,6,12,and 18 months postpartum
Friendship Bench for treatment of depression: a pilot study
30 SHINE mothers will be recruited to pilot a depression intervention for feasibility and acceptability
Measured: August 2018 - January 2019 (about a year after the end of the trial).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2013 (estimated)
- Study startNov 2012
- Primary completionJul 2017
- Study completion31 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Growth; Stunting, NutritionalStudies of the same condition, open and under way.
- More trials run by Johns Hopkins Bloomberg School of Public HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 5,280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins Bloomberg School of Public Health
- Sponsor type
- University, hospital or other
- Collaborators
- 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)
- Responsible party
- Principal investigator, Jean Humphrey, Johns Hopkins Bloomberg School of Public Health
- Investigators
- Jean H Humphrey, ScD, Principal investigator, Johns Hopkins University Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01824940
- Sponsor's protocol ID
- IRB00004205
- Other IDs
- R01HD060338
- Acronym
- SHINE
- Status last verified
- Jul 2018
- First submitted
- 27 Mar 2012
- Last updated
- 26 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Publications
Humphrey JH. Child undernutrition, tropical enteropathy, toilets, and handwashing. Lancet. 2009 Sep 19;374(9694):1032-1035. doi: 10.1016/S0140-6736(09)60950-8. No abstract available.
PubMed 19766883Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones A, Moulton LH, Stoltzfus RJ, Humphrey JH. Stunting is characterized by chronic inflammation in Zimbabwean infants. PLoS One. 2014 Feb 18;9(2):e86928. doi: 10.1371/journal.pone.0086928. eCollection 2014.
PubMed 24558364Paul KH, Muti M, Chasekwa B, Mbuya MN, Madzima RC, Humphrey JH, Stoltzfus RJ. Complementary feeding messages that target cultural barriers enhance both the use of lipid-based nutrient supplements and underlying feeding practices to improve infant diets in rural Zimbabwe. Matern Child Nutr. 2012 Apr;8(2):225-38. doi: 10.1111/j.1740-8709.2010.00265.x. Epub 2010 Aug 4.
PubMed 22405701Mbuya MN, Humphrey JH, Majo F, Chasekwa B, Jenkins A, Israel-Ballard K, Muti M, Paul KH, Madzima RC, Moulton LH, Stoltzfus RJ. Heat treatment of expressed breast milk is a feasible option for feeding HIV-exposed, uninfected children after 6 months of age in rural Zimbabwe. J Nutr. 2010 Aug;140(8):1481-8. doi: 10.3945/jn.110.122457. Epub 2010 Jun 23.
PubMed 20573941Ngure FM, Humphrey JH, Mbuya MN, Majo F, Mutasa K, Govha M, Mazarura E, Chasekwa B, Prendergast AJ, Curtis V, Boor KJ, Stoltzfus RJ. Formative research on hygiene behaviors and geophagy among infants and young children and implications of exposure to fecal bacteria. Am J Trop Med Hyg. 2013 Oct;89(4):709-16. doi: 10.4269/ajtmh.12-0568. Epub 2013 Sep 3.
PubMed 24002485Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Project Team. Hepcidin decreases over the first year of life in healthy African infants. Br J Haematol. 2014 Jan;164(1):150-3. doi: 10.1111/bjh.12567. Epub 2013 Sep 20. No abstract available.
PubMed 24112078Ngure FM, Reid BM, Humphrey JH, Mbuya MN, Pelto G, Stoltzfus RJ. Water, sanitation, and hygiene (WASH), environmental enteropathy, nutrition, and early child development: making the links. Ann N Y Acad Sci. 2014 Jan;1308:118-128. doi: 10.1111/nyas.12330.
PubMed 24571214Palha De Sousa CA, Brigham T, Chasekwa B, Mbuya MN, Tielsch JM, Humphrey JH, Prendergast AJ. Dosing of praziquantel by height in sub-Saharan African adults. Am J Trop Med Hyg. 2014 Apr;90(4):634-7. doi: 10.4269/ajtmh.13-0252. Epub 2014 Mar 3.
PubMed 24591432Gough EK, Moodie EE, Prendergast AJ, Johnson SM, Humphrey JH, Stoltzfus RJ, Walker AS, Trehan I, Gibb DM, Goto R, Tahan S, de Morais MB, Manges AR. The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014 Apr 15;348:g2267. doi: 10.1136/bmj.g2267.
PubMed 24735883Desai A, Mbuya MN, Chigumira A, Chasekwa B, Humphrey JH, Moulton LH, Pelto G, Gerema G, Stoltzfus RJ; SHINE Study Team. Traditional oral remedies and perceived breast milk insufficiency are major barriers to exclusive breastfeeding in rural Zimbabwe. J Nutr. 2014 Jul;144(7):1113-9. doi: 10.3945/jn.113.188714. Epub 2014 May 14.
PubMed 24828026Jones AD, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Stoltzfus RJ, Humphrey JH, Prendergast AJ. Acute illness is associated with suppression of the growth hormone axis in Zimbabwean infants. Am J Trop Med Hyg. 2015 Feb;92(2):463-70. doi: 10.4269/ajtmh.14-0448. Epub 2014 Dec 22.
PubMed 25535308Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Trial Team; Jones AD, Manges A, Mangwadu G, Maluccio JA, Mbuya MN, Ntozini R, Tielsch JM. Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants. PLoS One. 2015 Aug 7;10(8):e0135227. doi: 10.1371/journal.pone.0135227. eCollection 2015.
PubMed 26252205Gough EK, Stephens DA, Moodie EE, Prendergast AJ, Stoltzfus RJ, Humphrey JH, Manges AR. Linear growth faltering in infants is associated with Acidaminococcus sp. and community-level changes in the gut microbiota. Microbiome. 2015 Jun 13;3:24. doi: 10.1186/s40168-015-0089-2. eCollection 2015.
PubMed 26106478Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team; Humphrey JH, Jones AD, Manges A, Mangwadu G, Maluccio JA, Mbuya MN, Moulton LH, Ntozini R, Prendergast AJ, Stoltzfus RJ, Tielsch JM. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Rationale, Design, and Methods. Clin Infect Dis. 2015 Dec 15;61 Suppl 7(Suppl 7):S685-702. doi: 10.1093/cid/civ844.
PubMed 26602296Mbuya MN, Tavengwa NV, Stoltzfus RJ, Curtis V, Pelto GH, Ntozini R, Kambarami RA, Fundira D, Malaba TR, Maunze D, Morgan P, Mangwadu G, Humphrey JH; Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial Team. Design of an Intervention to Minimize Ingestion of Fecal Microbes by Young Children in Rural Zimbabwe. Clin Infect Dis. 2015 Dec 15;61 Suppl 7(Suppl 7):S703-9. doi: 10.1093/cid/civ845.
PubMed 26602297
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sanitation, Hygiene, Infant Nutrition Efficacy Project
- ClinicalTrials.gov ID
- NCT01824940
- Acronym / sponsor ID
- SHINE / IRB00004205
- Conditions
- Growth; Stunting, Nutritional, Anemia
- Keywords
- Cluster randomized trial, Nutrition, Water Sanitation Hygiene, Environmental enteropathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5,280 participants (actual)
- Lead sponsor
- Johns Hopkins Bloomberg School of Public HealthUniversity, hospital or other
- Collaborators
- 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)
- Study start
- Nov 2012
- Primary completion
- Jul 2017 (actual)
- Study completion
- 31 Jul 2017 (actual)
- First posted
- 5 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Standard of Care | Placebo comparator | Behavioral: Standard careThe Standard of Care interventions are the blanket interventions. |
| WASH | Active comparator | Other: WASHOne 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) |
| Nutrition | Active comparator | Dietary Supplement: Infant and young child feedingOne 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) |
| WASH and Nutrition | Active comparator | Other: WASH and NutritionThis arm receives a combination of all standard care interventions, all WASH and all IYCF interventions. |
Who may qualify
- Ages
- 15 to 49 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- Pregnant women residing in the study districts, whose pregnancy is confirmed by a urine pregnancy test.
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard careStandard 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 | Behavioural | Standard of Care |
| WASHWASH: * 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. | Other | WASH |
| Infant and young child feedingAlso: NutritionIYCF: * 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. | Dietary supplement | Nutrition |
| WASH and NutritionAlso: WASH and IYCFWASH AND IYCF interventions * Standard care interventions * All WASH interventions * All IYCF interventions | Other | WASH and Nutrition |
Primary outcome
Infant length at 18 months
Time frame: 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
Time frame: 18 months
Measured by Hemocue
18 secondary outcomes
Infant environmental enteric dysfunction
Time frame: 1, 3, 6, 12 and 18 months of age
Infant weight, mid-upper arm circumference and head circumference
Time frame: At 18 months, and (with length) at intermediate time-points of 1, 3, 6 and 12 months
To describe the Program Impact Pathways (PIP) linking implementation of each randomized intervention (WASH and IYCF) with length and hemoglobin concentrations
Time frame: Throughout follow-up
Exclusive breastfeeding
Time frame: First 6 months of life
To evaluate the effect of the IYCF intervention on uptake of improved infant feeding practices by maternal/infant HIV status
Time frame: 6-18 months of age
To evaluate the effect of the WASH intervention on the 5 key behaviors it promotes by maternal/infant HIV status
Time frame: Throughout follow-up
Relative contributions of diarrhea vs EED
Time frame: Birth to 18 months
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
Time frame: Throughout follow-up
Infant diarrhea prevalence, incidence and severity
Time frame: 1 month to 18 months of age
Child neurodevelopment
Time frame: 24 months of age
Prevalence of mycotoxin exposure among mothers and infants
Time frame: Maternal samples assessed at baseline; infant samples assessed birth to 18 months
MAternal and infant microbiota
Time frame: Maternal samples from baseline and 1 month postpartum; infant samples birth to 18 months of age
Infant rotavirus vaccine and polio vaccine immunogenicity
Time frame: 1 and 3 months of age
Adverse birth outcomes: miscarriage, still birth, small for gestational age, preterm delivery, neonatal death
Time frame: Maternal pregnancy exposures, infant outcomes through 1 month postpartum
Bioimpedance analysis, skinfold thicknesses and leg length measurement
Time frame: 24 months in a subsample of infants
Observational study of WASH and non-WASH infants
Time frame: About 14 months of age
Assess metabolic pathways of pathogenesis of stunting
Time frame: 12 month urines; longitudinal stools from 150 mother-infant pairs from 32 week gestation, and 1,3,6,12,and 18 months postpartum
Friendship Bench for treatment of depression: a pilot study
Time frame: August 2018 - January 2019 (about a year after the end of the trial).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- Background: PubMed 19766883Humphrey JH. Child undernutrition, tropical enteropathy, toilets, and handwashing. Lancet. 2009 Sep 19;374(9694):1032-1035. doi: 10.1016/S0140-6736(09)60950-8. No abstract available.
- Background: PubMed 24558364Prendergast AJ, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Jones A, Moulton LH, Stoltzfus RJ, Humphrey JH. Stunting is characterized by chronic inflammation in Zimbabwean infants. PLoS One. 2014 Feb 18;9(2):e86928. doi: 10.1371/journal.pone.0086928. eCollection 2014.
- Background: PubMed 22405701Paul KH, Muti M, Chasekwa B, Mbuya MN, Madzima RC, Humphrey JH, Stoltzfus RJ. Complementary feeding messages that target cultural barriers enhance both the use of lipid-based nutrient supplements and underlying feeding practices to improve infant diets in rural Zimbabwe. Matern Child Nutr. 2012 Apr;8(2):225-38. doi: 10.1111/j.1740-8709.2010.00265.x. Epub 2010 Aug 4.
- Background: PubMed 20573941Mbuya MN, Humphrey JH, Majo F, Chasekwa B, Jenkins A, Israel-Ballard K, Muti M, Paul KH, Madzima RC, Moulton LH, Stoltzfus RJ. Heat treatment of expressed breast milk is a feasible option for feeding HIV-exposed, uninfected children after 6 months of age in rural Zimbabwe. J Nutr. 2010 Aug;140(8):1481-8. doi: 10.3945/jn.110.122457. Epub 2010 Jun 23.
- Background: PubMed 24002485Ngure FM, Humphrey JH, Mbuya MN, Majo F, Mutasa K, Govha M, Mazarura E, Chasekwa B, Prendergast AJ, Curtis V, Boor KJ, Stoltzfus RJ. Formative research on hygiene behaviors and geophagy among infants and young children and implications of exposure to fecal bacteria. Am J Trop Med Hyg. 2013 Oct;89(4):709-16. doi: 10.4269/ajtmh.12-0568. Epub 2013 Sep 3.
- Background: PubMed 24112078Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Project Team. Hepcidin decreases over the first year of life in healthy African infants. Br J Haematol. 2014 Jan;164(1):150-3. doi: 10.1111/bjh.12567. Epub 2013 Sep 20. No abstract available.
- Background: PubMed 24571214Ngure FM, Reid BM, Humphrey JH, Mbuya MN, Pelto G, Stoltzfus RJ. Water, sanitation, and hygiene (WASH), environmental enteropathy, nutrition, and early child development: making the links. Ann N Y Acad Sci. 2014 Jan;1308:118-128. doi: 10.1111/nyas.12330.
- Background: PubMed 24591432Palha De Sousa CA, Brigham T, Chasekwa B, Mbuya MN, Tielsch JM, Humphrey JH, Prendergast AJ. Dosing of praziquantel by height in sub-Saharan African adults. Am J Trop Med Hyg. 2014 Apr;90(4):634-7. doi: 10.4269/ajtmh.13-0252. Epub 2014 Mar 3.
- Background: PubMed 24735883Gough EK, Moodie EE, Prendergast AJ, Johnson SM, Humphrey JH, Stoltzfus RJ, Walker AS, Trehan I, Gibb DM, Goto R, Tahan S, de Morais MB, Manges AR. The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials. BMJ. 2014 Apr 15;348:g2267. doi: 10.1136/bmj.g2267.
- Background: PubMed 24828026Desai A, Mbuya MN, Chigumira A, Chasekwa B, Humphrey JH, Moulton LH, Pelto G, Gerema G, Stoltzfus RJ; SHINE Study Team. Traditional oral remedies and perceived breast milk insufficiency are major barriers to exclusive breastfeeding in rural Zimbabwe. J Nutr. 2014 Jul;144(7):1113-9. doi: 10.3945/jn.113.188714. Epub 2014 May 14.
- Background: PubMed 25535308Jones AD, Rukobo S, Chasekwa B, Mutasa K, Ntozini R, Mbuya MN, Stoltzfus RJ, Humphrey JH, Prendergast AJ. Acute illness is associated with suppression of the growth hormone axis in Zimbabwean infants. Am J Trop Med Hyg. 2015 Feb;92(2):463-70. doi: 10.4269/ajtmh.14-0448. Epub 2014 Dec 22.
- Background: PubMed 26252205Mupfudze TG, Stoltzfus RJ, Rukobo S, Moulton LH, Humphrey JH, Prendergast AJ; SHINE Trial Team; Jones AD, Manges A, Mangwadu G, Maluccio JA, Mbuya MN, Ntozini R, Tielsch JM. Plasma Concentrations of Hepcidin in Anemic Zimbabwean Infants. PLoS One. 2015 Aug 7;10(8):e0135227. doi: 10.1371/journal.pone.0135227. eCollection 2015.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean H Humphrey, ScD principal investigator
Johns Hopkins University Bloomberg School of Public Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing WASH, Infant and young child feeding and WASH and Nutrition in people with Growth; Stunting, Nutritional and Anemia, run by Johns Hopkins Bloomberg School of Public Health at 1 site in Zimbabwe.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Zimbabwe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infant length at 18 months (time frame: 18 months of age. Protocol and Statistical Analysis Plan are available at https://osf.io/w93hy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01824940, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2018.