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Quadruple Fortified Salt (QFS) Trial in India (QFS)

Primary Purpose

Anemia, Folate Deficiency, Vitamin B 12 Deficiency

Status
Unknown status
Phase
Not Applicable
Locations
India
Study Type
Interventional
Intervention
+ Folic acid
+ Vitamin B12
DFS
Sponsored by
Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Anemia

Eligibility Criteria

18 Years - 49 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Severe anemia (Hemoglobin <8.0 g/dL)
  • HIV, active tuberculosis disease, or malaria infection
  • Malabsorption disorders (medical condition that may affect vitamin B12 absorption or metabolism)
  • Severe hypertension (SBP≥140 mm Hg or DBP≥90 mm Hg)
  • Other serious preexisting medical condition (i.e., defined as the need for regular medication use)
  • Daily micronutrient supplements (i.e., tablets, capsules, dispersible tablets; ≥4 times in the past week)
  • Intramuscular or intravenous interventions containing vitamin B12 or iron in the past 3 months

Sites / Locations

  • Arogyavaram Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Quadruple-Fortified Salt (QFS)

DFS + Folic acid

DFS + Vitamin B12

Double-fortified salt (DFS)

Arm Description

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

Salt fortified with iron, iodine, and folic acid

Salt fortified with iron, iodine, and vitamin B12

Salt fortified with iron and iodine

Outcomes

Primary Outcome Measures

Concentrations of erythrocyte folate and serum folate
Erythrocyte folate and serum folate concentrations, nmol/L
Concentrations of hemoglobin
Hemoglobin concentrations, g/dL
Concentrations of vitamin B12
Vitamin B12 concentrations, pmol/L

Secondary Outcome Measures

Folate deficiency and insufficiency
Erythrocyte (RBC) folate <305.0 nmol/L; <748.0 nmol/L
Anemia
Hemoglobin <12.0 g/dL
Vitamin B12 deficiency and insufficiency
Total vitamin B12 <148.0 pmol/L; <221.0 pmol/L

Full Information

First Posted
February 22, 2019
Last Updated
July 21, 2021
Sponsor
Cornell University
Collaborators
Centers for Disease Control and Prevention, Arogyavaram Medical Centre
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1. Study Identification

Unique Protocol Identification Number
NCT03853304
Brief Title
Quadruple Fortified Salt (QFS) Trial in India
Acronym
QFS
Official Title
A Randomized Trial of Quadruple Fortified Salt for Anemia and Birth Defects Prevention in Southern India
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
October 2021 (Anticipated)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cornell University
Collaborators
Centers for Disease Control and Prevention, Arogyavaram Medical Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Neural tube closure defects (NTDs) are a common adverse pregnancy outcome and among the most severe birth defects in the United States and globally. Women of reproductive age are a high-risk population for anemia and micronutrient deficiencies, and there is increasing evidence of the role of periconceptional nutritional status in the risk of birth defects and other common pregnancy complications. However, there is little representative population-level data from Southern India, where the burden of micronutrient deficiencies and birth defects is estimated to be among the highest in the world. Salt fortification is a promising strategy to prevent anemia and multiple micronutrient deficiencies, as it utilizes a widely consumed and affordable food and existing production and distribution systems. The objectives of this randomized controlled trial are to determine the efficacy of quadruple-fortified salt (QFS) - i.e., iron, iodine, folic acid, and vitamin B12 - on 1) erythrocyte folate and serum folate concentrations, 2) hemoglobin concentrations, and 3) vitamin B12 concentrations, among women of reproductive age in Southern India. If proven to be efficacious, QFS could represent a low-cost and sustainable strategy to prevent anemia and micronutrient deficiencies and improve the health of vulnerable populations, including women and young children.
Detailed Description
Neural tube closure defects (NTDs) are a common adverse pregnancy outcome, and one of the most debilitating birth defects in the United States and globally. NTDs comprise a cluster of neurodevelopmental conditions associated with the failure of neural tube closure during embryonic development. There are over 260,000 cases of NTDs each year globally, ranging from 1 to 80 per 10,000 births. Despite prevention efforts, NTDs remain a leading cause of neonatal morbidity and mortality worldwide, incurring medical costs of over $500,000 per person. Randomized trials have established that periconceptional folic acid supplementation prevents the occurrence and recurrence of NTDs by up to 70%. This led to the development of dietary recommendations for women of childbearing age in the U.S. and folic acid fortification of wheat and maize flour in over 80 countries. Fortification of food staples is a sustainable intervention to improve micronutrient status in populations, and fortification of flour with folic acid is considered one of the most efficacious and cost-effective public health interventions to date. However, current folic acid fortification programs have not eliminated NTDs, and are constrained by suboptimal coverage and lack of consumption of targeted staple foods by at-risk populations. Fortification efforts to date have mainly targeted wheat and maize flour, which are not primary staples in some settings with the highest NTD burden, such as Southern India. It is estimated that India alone accounts for over one-third of all NTDs globally. In Southern India, the site of this randomized trial, rice is the primary staple, and the persistent burden of micronutrient deficiencies underscores the need to innovate additional strategies to deliver folic acid to at-risk populations. Salt fortification is a promising strategy to prevent multiple micronutrient deficiencies, as it utilizes a widely consumed and affordable food and has existing production and distribution systems. In India, salt is one of the most widely consumed fortifiable staples. Previous studies demonstrated that double-fortified salt (DFS) with iron and iodine significantly improved iron status in women of reproductive age and schoolchildren. However, the high baseline prevalence of anemia and micronutrient deficiencies of folate and vitamin B12 persisted, highlighting a need for additional interventions to target multiple micronutrient deficiencies. Recent technological advances have informed the development of a low-cost formulation of quadruple-fortified salt (QFS) - i.e., iron, iodine, folic acid, and vitamin B12 (Diosady, Mannar). This QFS is formulated to prevent chemical interactions of micronutrients and maintain stability in tropical conditions, and is ready for use in randomized efficacy trials in human populations. The objectives of this randomized controlled trial are to determine the efficacy of quadruple-fortified salt (QFS) - i.e., iron, iodine, folic acid, and vitamin B12 - on 1) erythrocyte folate and serum folate concentrations, 2) hemoglobin concentrations, and 3) vitamin B12 concentrations, among women of reproductive age in Southern India. If proven to be efficacious, QFS could represent a low-cost and sustainable strategy to prevent anemia and micronutrient deficiencies and improve the the health of vulnerable populations, including women and young children.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Folate Deficiency, Vitamin B 12 Deficiency

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Model Description
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: Quadruple-fortified salt (QFS; i.e., iron, iodine, folic acid, and vitamin B12) DFS + folic acid DFS + vitamin B12; and Double-fortified salt (DFS; i.e., iron and iodine)
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
1000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Quadruple-Fortified Salt (QFS)
Arm Type
Experimental
Arm Description
Salt fortified with iron, iodine, folic acid, and vitamin B12
Arm Title
DFS + Folic acid
Arm Type
Experimental
Arm Description
Salt fortified with iron, iodine, and folic acid
Arm Title
DFS + Vitamin B12
Arm Type
Experimental
Arm Description
Salt fortified with iron, iodine, and vitamin B12
Arm Title
Double-fortified salt (DFS)
Arm Type
Active Comparator
Arm Description
Salt fortified with iron and iodine
Intervention Type
Other
Intervention Name(s)
+ Folic acid
Intervention Description
Salt fortified with folic acid
Intervention Type
Other
Intervention Name(s)
+ Vitamin B12
Intervention Description
Salt fortified with vitamin B12
Intervention Type
Other
Intervention Name(s)
DFS
Intervention Description
Salt fortified with iron and iodine
Primary Outcome Measure Information:
Title
Concentrations of erythrocyte folate and serum folate
Description
Erythrocyte folate and serum folate concentrations, nmol/L
Time Frame
Endline (12 months)
Title
Concentrations of hemoglobin
Description
Hemoglobin concentrations, g/dL
Time Frame
Endline (12 months)
Title
Concentrations of vitamin B12
Description
Vitamin B12 concentrations, pmol/L
Time Frame
Endline (12 months)
Secondary Outcome Measure Information:
Title
Folate deficiency and insufficiency
Description
Erythrocyte (RBC) folate <305.0 nmol/L; <748.0 nmol/L
Time Frame
Endline (12 months)
Title
Anemia
Description
Hemoglobin <12.0 g/dL
Time Frame
Endline (12 months)
Title
Vitamin B12 deficiency and insufficiency
Description
Total vitamin B12 <148.0 pmol/L; <221.0 pmol/L
Time Frame
Endline (12 months)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: Severe anemia (Hemoglobin <8.0 g/dL) HIV, active tuberculosis disease, or malaria infection Malabsorption disorders (medical condition that may affect vitamin B12 absorption or metabolism) Severe hypertension (SBP≥140 mm Hg or DBP≥90 mm Hg) Other serious preexisting medical condition (i.e., defined as the need for regular medication use) Daily micronutrient supplements (i.e., tablets, capsules, dispersible tablets; ≥4 times in the past week) Intramuscular or intravenous interventions containing vitamin B12 or iron in the past 3 months
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julia L Finkelstein, MPH SM ScD
Phone
+1.607.255.9180
Email
jfinkelstein@cornell.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julia L Finkelstein, MPH SM ScD
Organizational Affiliation
Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arogyavaram Medical Centre
City
Madanapalle
State/Province
Andhra Pradesh
Country
India
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wesley Bonam, MBBS
First Name & Middle Initial & Last Name & Degree
Christina Johnson, MS
First Name & Middle Initial & Last Name & Degree
Wesley Bonam, MBBS

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33122315
Citation
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.
Results Reference
background
PubMed Identifier
34027296
Citation
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.
Results Reference
result

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Quadruple Fortified Salt (QFS) Trial in India

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