Clinical trial NCT05166980: Study of Multiply-fortified Salt Among Women of Reproductive Age and Preschool Children in India
Official title: Study of Multiply-fortified Salt Among Women of Reproductive Age and Preschool Children in India
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nutrient Deficiency
Keywords: Micronutrient deficiencies
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Post Graduate Institute of Medical Education and Research, Chandigarh
name: University of California, Davis
name: University of Colorado, Denver
First posted: 2021-12-22
Enrollment: 1389
Sex: ALL
Minimum age (years): 12
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3-armed, double-blind, community-based efficacy trial
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in serum ferritin
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in hemoglobin
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in soluble transferrin
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in red blood cell folate
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in plasma zinc
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in serum vitamin B12
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in holo-transcobalamin
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in methylmalonic acid
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in serum folate
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in urinary iodine
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in serum thyroglobulin
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
Secondary outcomes:
measure: Change in nail zinc
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
measure: Change in gut microbiota
timeFrame: Enrollment to 12 months (i.e. end of intervention period)
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research, Chandigarh
Study officials:
affiliation: University of California, San Francisco
name: Christine McDonald, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.