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

NCT05166980 | Completed DMC

• 1 other identifier: MFS_1.2
• Study Type: interventional
• Target: 1,389
• Locations: 1 country
• Sites: 1

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.

Conditions

Nutrient Deficiency

Keywords

Micronutrient deficiencies

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (2)

• Change in nail zinc

  Enrollment to 12 months (i.e. end of intervention period)

• Change in gut microbiota

  Enrollment to 12 months (i.e. end of intervention period)

Study Arms (3)

FePP-Q5S

EXPERIMENTAL

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

eFF-Q5S

EXPERIMENTAL

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

Iodized Salt

ACTIVE COMPARATOR

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

Interventions

Mutiply-fortified salt DIETARY_SUPPLEMENT

Salt fortified with iron, zinc, vitamin B12, folic acid, and iodine

Also known as: Quintuply-fortified salt

FePP-Q5S; eFF-Q5S

Iodized salt DIETARY_SUPPLEMENT

Salt fortified with iodine

Also known as: Salt fortified with iodine

Iodized Salt

Eligibility Criteria

• Age: 12 Months - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Child age \< 12 or \> 59 months of age;
• Child's mother has not been enrolled in the parent trial;

Sponsors & Collaborators

• University of California, San Francisco: lead
• Post Graduate Institute of Medical Education and Research, Chandigarh: collaborator
• University of California, Davis: collaborator
• University of Colorado, Denver: collaborator

Study Sites (1)

Postgraduate Institute of Medical Education and Research, Chandigarh

Chandigarh, India

Location

Related Publications (3)

• Thompson L, Goh YE, Jamwal M, Singh BL, Brar GK, Arnold CD, Westcott J, Long JM, Krebs NF, Zivkovic A, Das R, Duggal M, McDonald CM. The Effect of Quintuply-Fortified Salt on the Gut Microbiome of Young Children 1-5 y of Age in Punjab, India; A Substudy of a Randomized, Community-Based Trial. Curr Dev Nutr. 2025 Oct 23;9(11):107580. doi: 10.1016/j.cdnut.2025.107580. eCollection 2025 Nov.

  PMID: 41323692 DERIVED

• Goh YE, Duggal M, Das R, Manger MS, Jamwal M, Singh BL, Brar GK, Long JM, Westcott J, Thompson L, Arnold CD, Krebs NF, Brown KH, McDonald CM. Effects of quintuply-fortified salt on the micronutrient status of females of reproductive age in Punjab, India: a randomized, community-based trial. Am J Clin Nutr. 2025 Jul;122(1):146-156. doi: 10.1016/j.ajcnut.2025.04.009. Epub 2025 Jun 6.

  PMID: 40610127 DERIVED

• 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.

  PMID: 36068647 DERIVED

MeSH Terms

Interventions

iodized salt; Iodine

Intervention Hierarchy (Ancestors)

Halogens; Elements; Inorganic Chemicals

Study Officials

• Christine McDonald, ScD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study salts will be packaged in color-coded, polyethylene bags.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3-armed, double-blind, community-based efficacy trial

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: December 22, 2021
• Study Start: October 17, 2022
• Primary Completion: May 2, 2024
• Study Completion: May 2, 2024
• Last Updated: May 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• 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.

Locations

IN (1)