Quadruple Fortified Salt Trial in India

NCT03853304 | Active Not Recruiting DMC

• 1 other identifier: 86613
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

Women of reproductive age are at an increased risk of anemia and micronutrient deficiencies. Evidence supports the role of periconceptional nutrition in the development of neural tube defects and other pregnancy complications. Vitamin B12 deficiency is a risk factor for neural tube defects and may modify folate biomarkers that predict neural tube defect risk at the population level. There is an interest in mandatory fortification with vitamin B12 and folic acid for anemia and birth defect prevention. However, there are limited population-representative data needed to inform policy and guidelines. This randomized trial will be conducted to evaluate the efficacy of quadruple-fortified salt (QFS; iron, iodine, folic acid, vitamin B12) in 1,000 women and their households in Southern India.

Conditions

Anemia; Folate Deficiency; Vitamin B 12 Deficiency

Outcome Measures

Primary Outcomes (3)

• Concentrations of erythrocyte folate and serum folate

  Erythrocyte folate and serum folate concentrations, nmol/L

  Endpoint (12 months)

• Concentrations of hemoglobin

  Hemoglobin concentrations, g/dL

  Endpoint (12 months)

• Concentrations of vitamin B12

  Vitamin B12 concentrations, pmol/L

  Endpoint (12 months)

Secondary Outcomes (3)

• Folate deficiency and insufficiency

  Endpoint (12 months)

• Anemia

  Endpoint (12 months)

• Vitamin B12 deficiency and insufficiency

  Endpoint (12 months)

Study Arms (4)

Quadruple-Fortified Salt (QFS)

EXPERIMENTAL

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

Other: + Folic acid; Other: + Vitamin B12; Other: DFS

DFS + Folic acid

EXPERIMENTAL

Salt fortified with iron, iodine, and folic acid

Other: + Folic acid; Other: DFS

DFS + Vitamin B12

EXPERIMENTAL

Salt fortified with iron, iodine, and vitamin B12

Other: + Vitamin B12; Other: DFS

Double-fortified salt (DFS)

ACTIVE COMPARATOR

Salt fortified with iron and iodine

Other: DFS

Interventions

+ Folic acid OTHER

Salt fortified with folic acid

DFS + Folic acid; Quadruple-Fortified Salt (QFS)

+ Vitamin B12 OTHER

Salt fortified with vitamin B12

DFS + Vitamin B12; Quadruple-Fortified Salt (QFS)

DFS OTHER

Salt fortified with iron and iodine

DFS + Folic acid; DFS + Vitamin B12; Double-fortified salt (DFS); Quadruple-Fortified Salt (QFS)

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women between 18 and 49 years of age
• Healthy
• Not pregnant or lactating
• Plan to reside in the catchment area of our periconceptional surveillance program for at least two years

You may not qualify if:

• Severe anemia (Hemoglobin \<8.0 g/dL)
• Reported diagnosis of HIV, malaria infection, or active tuberculosis disease
• Malabsorption disorders (i.e., medical conditions that may affect vitamin B12 absorption or metabolism)
• Stage 2 hypertension (SBP≥140 mm Hg or DBP≥90 mm Hg)
• Glycated hemoglobin (HbA1c) ≥6.5%
• Other serious pre-existing medical conditions (e.g., defined as the need for regular medication use), active infections, or acute illnesses
• Previous pregnancy affected by a neural tube defect (i.e., who have had a fetus diagnosed as affected by a neural tube defect or have given birth to a baby with a neural tube defect) (will be referred to OB/GYN for standard of care, including folic acid supplementation, and excluded)
• Planning to become pregnant (or planning to have a child) in the next 12 months (will be referred to OB/GYN for standard of care, including folic acid supplementation, and be excluded)
• Daily micronutrient supplements (i.e., tablets, capsules, dispersible tablets; ≥4 times in the past week)
• Intramuscular or intravenous interventions containing medications or micronutrients (e.g., iron, vitamin B12, folic acid) in the past 3 months

Sponsors & Collaborators

• Cornell University: lead
• Centers for Disease Control and Prevention: collaborator
• Arogyavaram Medical Centre: collaborator

Study Sites (1)

Arogyavaram Medical Centre

Madanapalle, Andhra Pradesh, India

Location

Related Publications (5)

• Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar S, Zhang M, Pfeiffer CM, Qi YP, Rose CE, Williams JL, Bonam W, Crider KS. Anemia and Vitamin B-12 and Folate Status in Women of Reproductive Age in Southern India: Estimating Population-Based Risk of Neural Tube Defects. Curr Dev Nutr. 2021 Apr 26;5(5):nzab069. doi: 10.1093/cdn/nzab069. eCollection 2021 May.

  PMID: 34027296 BACKGROUND

• Finkelstein JL, Fothergill A, Johnson CB, Guetterman HM, Bose B, Jabbar S, Zhang M, Pfeiffer CM, Qi YP, Rose CE, Krisher JT, Ruth CJ, Mehta R, Williams JL, Bonam W, Crider KS. Periconceptional surveillance for prevention of anaemia and birth defects in Southern India: protocol for a biomarker survey in women of reproductive age. BMJ Open. 2020 Oct 29;10(10):e038305. doi: 10.1136/bmjopen-2020-038305.

  PMID: 33122315 BACKGROUND

• Finkelstein JL, Guetterman HM, Fothergill A, Johnson CB, Qi YP, Jabbar S, Zhang M, Pfeiffer CM, Rose CE, Yeung LF, Williams JL, Krisher JT, Ruth C, Roy Choudhury D, Venkatramanan S, Haas JD, Kuriyan R, Mehta S, Bonam W, Crider KS. A Randomized Trial of Quadruple-Fortified Salt for Anemia and Birth Defects Prevention in Southern India: Protocol Design and Methods. Curr Dev Nutr. 2023 Feb 21;7(3):100052. doi: 10.1016/j.cdnut.2023.100052. eCollection 2023 Mar.

  PMID: 37181934 BACKGROUND

• Finkelstein JL, Fothergill A, Guetterman HM, Johnson CB, Bose B, Qi YP, Rose CE, Williams JL, Mehta S, Kuriyan R, Bonam W, Crider KS. Iron status and inflammation in women of reproductive age: A population-based biomarker survey and clinical study. Clin Nutr ESPEN. 2022 Jun;49:483-494. doi: 10.1016/j.clnesp.2022.02.123. Epub 2022 Mar 5.

  PMID: 35623855 BACKGROUND

• Guetterman HM, Rajagopalan K, Fox AM, Johnson CB, Fothergill A, George N, Krisher JT, Haas JD, Mehta S, Williams JL, Crider KS, Finkelstein JL. A Randomized Crossover Trial of Acceptability of Quadruple-Fortified Salt in Women and their Households in Southern India. J Nutr. 2025 Jan;155(1):322-337. doi: 10.1016/j.tjnut.2024.10.037. Epub 2024 Oct 26.

  PMID: 39490799 DERIVED

MeSH Terms

Conditions

Anemia; Folic Acid Deficiency; Vitamin B 12 Deficiency

Interventions

Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Julia L Finkelstein, MPH SM ScD

  Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All salt formulations will be similar in taste, appearance, and texture. Salt will be packaged in bags labeled with color codes known only to the salt manufacturers and a statistician unaffiliated with the study. A statistician unaffiliated with this study will generate a random number sequence for intervention allocation. Blinding will be maintained until initial data analysis is completed.
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: After confirming eligibility and informed consent/assent, women will be randomly assigned to one of the 4 intervention arms, using a 2 X 2 factorial design: 1. Quadruple-fortified salt (QFS; i.e., iron, iodine, folic acid, and vitamin B12) 2. DFS + folic acid 3. DFS + vitamin B12; and 4. Double-fortified salt (DFS; i.e., iron and iodine)

Study Record Dates

• First Submitted: February 22, 2019
• First Posted: February 25, 2019
• Study Start: October 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 1, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)