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

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.

Study Overview

• Status: Completed
• Conditions: Nutrient Deficiency
• Intervention / Treatment: Dietary supplement: Mutiply-fortified salt; Dietary supplement: Iodized salt

• Study Type: Interventional
• Enrollment (Actual): 1389
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Chandigarh, India
    • Postgraduate Institute of Medical Education and Research, Chandigarh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 49 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria for women of reproductive age:

1. 18-49 years of age;
2. Not currently pregnant (self-reported);
3. Not severely anemia (defined as a hemoglobin concentration < 8 g/dL);
4. Not planning to become pregnant within the next year;
5. 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;
6. No serious health problems that requires regular visits to a health facility;
7. Willingness to use refined salt provided by the study as a primary source of household discretionary salt.

Exclusion criteria for women of reproductive age:

1. Age <18 or > 49 years of age;
2. Pregnant at the time of enrollment (self report) or planning to become pregnant within the next year;
3. Severely anemic (i.e. hemoglobin concentration < 8 g/dL);
4. Not a permanent resident of the study area;
5. Planning to leave the study area for at least one month over the study period;
6. Serious health problem that interferes with eating practices and/or requires hospitalization;
7. Unwilling to use refined salt provided by the study as the primary source of the household's discretionary salt.

Inclusion criteria for preschool children:

1. Child 12-59 months of age at the time of enrollment;
2. Child's mother or primary female caregiver has been enrolled into the parent trial;
3. Not severely anemic (defined as a hemoglobin concentration < 7 g/dL);
4. 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;
5. No serious medical problems that interfere with the child's eating practices;
6. 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:

1. Child age < 12 or > 59 months of age;
2. Child's mother has not been enrolled in the parent trial;
3. Severely anemic (i.e. hemoglobin concentration < 7 g/dL);
4. 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;
5. Serious health problem that interferes with the child's eating practices;
6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FePP-Q5S; 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; Salt fortified with iron, zinc, vitamin B12, folic acid, and iodine; Other Names: Quintuply-fortified salt
Experimental: eFF-Q5S; 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; Salt fortified with iron, zinc, vitamin B12, folic acid, and iodine; Other Names: Quintuply-fortified salt
Active Comparator: Iodized Salt; 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; Salt fortified with iodine; 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)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: University of Colorado, Denver; University of California, Davis; Post Graduate Institute of Medical Education and Research, Chandigarh
• Investigators: Principal Investigator: Christine McDonald, ScD, University of California, San Francisco

Publications and helpful links

General Publications

• McDonald CM, Brown KH, Goh YE, Manger MS, Arnold CD, Krebs NF, Westcott J, Long JM, Gibson RS, Jamwal M, Singh BL, Dahiya N, Budhija D, Das R, Duggal M. Quintuply-fortified salt for the improvement of micronutrient status among women of reproductive age and preschool-aged children in Punjab, India: protocol for a randomized, controlled, community-based trial. BMC Nutr. 2022 Sep 6;8(1):98. doi: 10.1186/s40795-022-00583-y.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): May 2, 2024
• Study Completion (Actual): May 2, 2024

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Estimated): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Micronutrient deficiencies
• Other Study ID Numbers: MFS_1.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: As soon as the manuscripts summarizing the study's primary outcomes are published, all datasets will be posted to Open Science Framework and made available to the public in accordance with the Gates Foundation's Open Data Policy.
• IPD Sharing Time Frame: Data will become available as soon as the manuscripts summarizing the study's primary endpoints have been published. Data will be made available indefinitely.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No