Study of Multiply-fortified Salt Among Women of Reproductive Age and Preschool Children in India

Study Overview
=================
Brief Summary
-----------------
Micronutrient (MN) deficiencies are highly prevalent in India, particularly among women of reproductive age (WRA) and preschool aged children (PSC). MN fortification of a staple food or condiment can be an effective strategy for improving the MN status of nutritionally vulnerable populations, as the approach is cost-effective, utilizes existing delivery systems, can deliver multiple MNs simultaneously, and does not require behavior change by the population. Salt is a particularly attractive vehicle for multiple MN fortification in India, as it is universally consumed in fairly consistent amounts; and 93% of households already use adequately iodized salt. The overall goal of this study is to evaluate the nutritional impact of quintuply-fortified salt with iron in the form of FePP (FePP-Q5S, i.e. salt fortified with iron in the form of ferric pyrophosphate plus ethylenediaminetetraacetic acid as an enhancer of absorption; zinc in the form of zinc oxide; vitamin B12; folic acid; and iodine) vs. quintuply-fortified salt with iron in the form of eFF (eFF-Q5S i.e. salt fortified with iron in the form of encapsulated ferrous fumarate; zinc in the form of zinc oxide, vitamin B12, folic acid, and iodine) vs. iodized salt (IS) for the improvement of micronutrient status among nonpregnant WRA and preschool-aged children (12-59 months of age) in Punjab, India. Enrolled women (and their affiliated households) will be randomized to receive 1 kg of their assigned study salt per month for 12 months, and will be instructed to use the study salt in place of their usual salt. Blood and urine samples will be collected from participant WRA and PSC at enrollment, 6 months and at the end of the 12-month intervention period. The change in the mean concentration of various MN biomarkers will be considered primary outcomes. Stool samples will also be collected from a subgroup of women and children to assess changes in the gut microbiome over the intervention period.

Official Title
-----------------
Study of Multiply-fortified Salt Among Women of Reproductive Age and Preschool Children in India

Conditions
-----------------
Nutrient Deficiency

Intervention / Treatment
-----------------
* Dietary Supplement: Mutiply-fortified salt
* Dietary Supplement: Iodized salt


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria for women of reproductive age: 18-49 years of age; Not currently pregnant (self-reported); Not severely anemia (defined as a hemoglobin concentration < 8 g/dL); Not planning to become pregnant within the next year; Permanent resident of the study village with no plans to move or travel outside the village for more than 4 weeks over the next 12 months; No serious health problems that requires regular visits to a health facility; Willingness to use refined salt provided by the study as a primary source of household discretionary salt. Exclusion criteria for women of reproductive age: Age <18 or > 49 years of age; Pregnant at the time of enrollment (self report) or planning to become pregnant within the next year; Severely anemic (i.e. hemoglobin concentration < 8 g/dL); Not a permanent resident of the study area; Planning to leave the study area for at least one month over the study period; Serious health problem that interferes with eating practices and/or requires hospitalization; Unwilling to use refined salt provided by the study as the primary source of the household's discretionary salt. Inclusion criteria for preschool children: Child 12-59 months of age at the time of enrollment; Child's mother or primary female caregiver has been enrolled into the parent trial; Not severely anemic (defined as a hemoglobin concentration < 7 g/dL); Child's family is a permanent resident of the study village with no plans to move or travel outside the village for more than 4 weeks over the next 12 months; No serious medical problems that interfere with the child's eating practices; Child's mother or primary female caregiver is willing to use refined salt provided by the study as the primary source of the household's discretionary salt for the course of the study. Exclusion criteria for preschool children: Child age < 12 or > 59 months of age; Child's mother has not been enrolled in the parent trial; Severely anemic (i.e. hemoglobin concentration < 7 g/dL); Child's family is not a permanent resident of the study village and/or has plans to travel outside the village for more than 4 weeks over the next 12 months; Serious health problem that interferes with the child's eating practices; Child's mother or primary female caregiver is unwilling to use refined salt provided by the study as the primary sources of the household's discretionary salt for the course of the study.

Ages Eligible for Study
-----------------
Minimum Age: 12 Months
Maximum Age: 49 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 3-armed, double-blind, community-based efficacy trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FePP-Q5S<br>Salt fortified with iron in the form of ferric pyrophosphate (at 1.3 mg of iron per gram of salt) plus ethylenediaminetetraacetic acid (EDTA) as an enhancer of absorption, zinc in the form of zinc oxide (at 1.4 mg of zinc per gram of salt), vitamin B12 (at 0.6 ug of vitamin B12 per gram of salt), folic acid (at 52 ug per gram of salt) and iodine (at 30 mg of iodine per gram of salt). Mean intake of discretionary salt among women of reproductive age in the study area is 4.6 grams per day. Therefore, the FePP-Q5S will deliver an average of 6.0 mg of iron, 6.4 mg of zinc, 2.8 ug of vitamin B12, 241 ug of folic acid, and 138 mg of iodine to each participating woman per day. | Dietary Supplement: Mutiply-fortified salt<br>* Salt fortified with iron, zinc, vitamin B12, folic acid, and iodine<br>* Other names: Quintuply-fortified salt;|
| Experimental: eFF-Q5S<br>Salt fortified with iron in the form of encapsulated ferrous fumarate (at 1.3 mg of iron per gram of salt), zinc in the form of zinc oxide (at 1.4 mg of zinc per gram of salt), vitamin B12 (at 0.6 ug of vitamin B12 per gram of salt), folic acid (at 52 ug per gram of salt) and iodine (at 30 mg of iodine per gram of salt). Mean intake of discretionary salt among women of reproductive age in the study area is 4.6 grams per day. Therefore, the eFF-Q5S will deliver an average of 6.0 mg of iron, 6.4 mg of zinc, 2.8 ug of vitamin B12, 241 ug of folic acid, and 138 mg of iodine to each participating woman per day. | Dietary Supplement: Mutiply-fortified salt<br>* Salt fortified with iron, zinc, vitamin B12, folic acid, and iodine<br>* Other names: Quintuply-fortified salt;|
| Active Comparator: Iodized Salt<br>Iodized salt containing 30 mg of iodine per gram of salt. Mean intake of discretionary salt among women of reproductive age in the study area is 4.6 grams per day. Therefore, the iodized salt will deliver an average of 138 mg of iodine to each participating woman per day. | Dietary Supplement: Iodized salt<br>* Salt fortified with iodine<br>* Other names: Salt fortified with iodine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum ferritin | Change in inflammation-adjusted mean serum ferritin concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in hemoglobin | Change in mean hemoglobin concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in soluble transferrin | Change in inflammation-adjusted mean soluble transferrin concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in red blood cell folate | Change in mean red blood cell folate concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in plasma zinc | Change in mean plasma zinc concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in serum vitamin B12 | Change in mean serum vitamin B12 concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in holo-transcobalamin | Change in mean holo-transcobalamin concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in methylmalonic acid | Change in mean concentration of methylmalonic acid | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in serum folate | Change in mean serum folate concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in urinary iodine | Change in mean urinary iodine concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in serum thyroglobulin | Change in mean serum thyroglobulin concentration | Enrollment to 12 months (i.e. end of intervention period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in nail zinc | Change in mean fingernail zinc concentration | Enrollment to 12 months (i.e. end of intervention period) | 
| Change in gut microbiota | Change in the abundance of potentially beneficial microbiota in the gut | Enrollment to 12 months (i.e. end of intervention period) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Micronutrient deficiencies