Acceptability and Nutritional Impact of Double-fortified Salt Containing Iodine and Folic Acid

NCT06223854 | Completed DMC

• 1 other identifier: 2078626
• Study Type: interventional
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching objective of this two-phase project is to assess the effects of fortifying iodized salt with folic acid on improving women's folate status. Folate insufficiency is the primary risk factor for neural tube defects (NTDs), which are highly prevalent in Ethiopia. The purposes of Phase 2 of the project, described herein, are to complete a community-based, randomized, dose-response intervention trial of edible salt fortified with just iodine or iodine and one of two levels of folic acid among non-pregnant women of reproductive age (WRA), We will assess the effects of the intervention on women's discretionary salt intakes, markers of folate and iodine status, and incidence of any adverse events.

Conditions

Folate Deficiency; Iodine Deficiency; Anemia Macrocytic; Anemia Deficiency; Salt Intake; Vitamin B 12 Deficiency

Keywords

Salt fortification; Ethiopia

Outcome Measures

Primary Outcomes (6)

• Red blood cell folate

  Red blood cell (RBC) folate concentration will be measured on three occasions in each participant: 1) before the start of the intervention, 2) at a randomly assigned mid-point between 4 and 20 weeks after the start of the intervention, and 3) between 24-26 weeks after the start of the intervention. RBC folate concentration will be will be determined by using a microbiological assay.

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum folate

  Serum folate concentration will be measured on three occasions in each participant: 1) before the start of the intervention, 2) at a randomly assigned mid-point between 4 and 20 weeks after the start of the intervention, and 3) between 24-26 weeks after the start of the intervention, by using a microbiological assay.

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum homocysteine

  Serum homocysteine concentration will be measured on three occasions in each participant: 1) before the start of the intervention, 2) at a randomly assigned mid-point between 4 and 20 weeks after the start of the intervention, and 3) between 24-26 weeks after the start of the intervention.

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum thyroglobulin

  Serum thyroglobulin concentration will be measured on three occasions in each participant: 1) before the start of the intervention, 2) at a randomly assigned mid-point between 4 and 20 weeks after the start of the intervention, and 3) between 24-26 weeks after the start of the intervention.

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• 24-hour urinary iodine excretion

  24-hour urinary iodine excretion will be measured prior to the start of the intervention and at a second time time at least 4 weeks after the start of the intervention.

  Before and during the intervention

• Serious adverse events

  Serious adverse events requiring an overnight stay in a clinical facility or resulting in disability, or death will be recorded during each bi-weekly home visit.

  Throughout the course of the intervention, total of 26 weeks

Secondary Outcomes (9)

• Hemoglobin concentration

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum B12

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum transcobalamin

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum methyl malonic acid

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

• Serum unmetabolized folic acid

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

Other Outcomes (1)

• Blood pressure

  Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

Study Arms (3)

Iodized salt

ACTIVE COMPARATOR

Refined iodized salt containing 35 ppm iodine as potassium iodate

Dietary Supplement: Iodized salt

Iodized salt with lower-dose folic acid fortification

EXPERIMENTAL

Refined iodized salt containing 35 ppm iodine as potassium iodate and 33 ppm folic acid (to provide an estimated 200 microgram folic acid per day to women consuming the previously determined average amount of discretionary salt in the study communities)

Dietary Supplement: Experimental: Iodized salt with lower-dose folic acid fortification

Iodized salt with higher-dose folic acid fortification

EXPERIMENTAL

Refined iodized salt containing 35 ppm iodine as potassium iodate and 99 ppm folic acid (to provide an estimated 600 microgram folic acid per day to women consuming the previously average amount of discretionary salt in the study communities)

Dietary Supplement: Experimental: Iodized salt with higher-dose folic acid fortification

Interventions

Iodized salt DIETARY_SUPPLEMENT

Masked, individually labeled 500-g containers of the study salts will be delivered to the participants' homes bi-weekly by field workers who will collect previously delivered salt containers during the same visit. Participants will be counseled to use the study salt for all food preparation and meal-time seasoning for all members of the household and not to share the salt with others or use it for non-food consumption purposes.

Iodized salt

Experimental: Iodized salt with lower-dose folic acid fortification DIETARY_SUPPLEMENT

Masked, individually labeled 500-g containers of the study salts will be delivered to the participants' homes bi-weekly by field workers who will collect previously delivered salt containers during the same visit. Participants will be counseled to use the study salt for all food preparation and meal-time seasoning for all members of the household and not to share the salt with others or use it for non-food consumption purposes.

Iodized salt with lower-dose folic acid fortification

Experimental: Iodized salt with higher-dose folic acid fortification DIETARY_SUPPLEMENT

Masked, individually labeled 500-g containers of the study salts will be delivered to the participants' homes bi-weekly by field workers who will collect previously delivered salt containers during the same visit. Participants will be counseled to use the study salt for all food preparation and meal-time seasoning for all members of the household and not to share the salt with others or use it for non-food consumption purposes.

Iodized salt with higher-dose folic acid fortification

Eligibility Criteria

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

You may qualify if:

• Non-pregnant
• Using long-acting contraceptive
• Intending to remain in study community for at least six months
• Willing to use study salt for all household food preparation and seasoning
• Signed, informed consent

You may not qualify if:

• Pregnant
• Not using long-acting contraceptive
• Acute or chronic disease that affects dietary intake or folate metabolism
• Hypertension
• Medications that potentially interfere with folate metabolism
• Folic acid-containing vitamin supplements
• Macrocytic anemia or moderate/severe non-macrocytic anemia.
• Mid-upper arm circumference \<23 cm and breast feeding an infant \<6 months of age

Sponsors & Collaborators

• University of California, Davis: lead
• Ethiopian Public Health Institute: collaborator
• University of California, San Francisco: collaborator
• University of Rhode Island: collaborator
• Nutrition International: collaborator

Study Sites (1)

Ethiopian Public Health Institute

Addis Ababa, Ethiopia

Location

Related Publications (2)

• Brown KH, Tessema M, McDonald CM, Agbemafle I, Woldeyohannes M, Fereja M, Nane D, Arnold CD, Waka FC, Tesfaye B, Arabi M, Martinez H. Protocol for a community-based, household-randomised, dose-response trial to assess the acceptability, nutritional effects and safety of double-fortified salt containing iodine and folic acid compared with iodised salt among non-pregnant Ethiopian women of reproductive age (DFS-IoFA). BMJ Open. 2024 Oct 29;14(10):e084494. doi: 10.1136/bmjopen-2024-084494.

  PMID: 39477275 BACKGROUND

• Tessema M, Nane D, Woldeyohannes M, Agbemafle I, McDonald CM, Arnold CD, Fereja M, Challa F, Martinez H, Tesfaye B, Tollera G, Arabi M, Brown KH; Collaborating Laboratories. Folic acid fortification of iodized salt improves the folate status of non-pregnant adult Ethiopian females and does not impair their iodine status: a community-based, household-randomized, dose-response trial. Am J Clin Nutr. 2026 Jan 27:101204. doi: 10.1016/j.ajcnut.2026.101204. Online ahead of print.

  PMID: 41611087 DERIVED

MeSH Terms

Conditions

Folic Acid Deficiency; Anemia, Macrocytic; Vitamin B 12 Deficiency

Interventions

iodized salt

Condition Hierarchy (Ancestors)

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

Study Officials

• KENNETH H BROWN, MD

  UC Davis

  PRINCIPAL INVESTIGATOR

• Masresha Tessema, PhD

  Ethiopian Public Health Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The salts will be packaged in 500-gram plastic containers (canisters) labeled with the participants' study identification number. Two containers of salt will be delivered to the participants' homes every two weeks, at which time the previously delivered canisters will be collected..
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a community-based, three-arm, randomized, dose-response intervention trial with randomization at the level of the household of non-pregnant women of reproductive age.

Study Record Dates

• First Submitted: January 3, 2024
• First Posted: January 25, 2024
• Study Start: April 25, 2024
• Primary Completion: December 16, 2024
• Study Completion: December 16, 2024
• Last Updated: March 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: The study protocol will be submitted for publication prior to initiation of Phase 2. The statistical analysis plan will be publicly available prior to the start of the respective analyses. The informed consent documents will be available (in English and Afaan Oromo) .
• Access Criteria: As indicated above.

Locations

ET (1)