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Folate DeficiencyDFS-IoFA-2NCT06223854

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

A study testing Iodized salt, Experimental: Iodized salt with lower-dose folic acid fortification and Experimental: Iodized salt with higher-dose folic acid fortification in people with Folate Deficiency and Iodine Deficiency, run by University of California, Davis at 1 site in Ethiopia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 49 years, women onlyHealthy volunteers can take part
What is being tested?
Iodized salt, Experimental: Iodized salt with lower-dose folic acid fortification and Experimental: Iodized salt with higher-dose folic acid fortification
Could I receive a placebo?
No, everyone receives an active treatment
How many people
360 participants
Where
1 siteEthiopia
Study dates
25 Apr 2024to 16 Dec 2024
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 49 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Ethiopia1 site
  • Ethiopian Public Health Institute

    Addis Ababa

Other trials in Ethiopia

About this study

Official title: Evaluation of the Acceptability and Nutritional Effects of Double-fortified Salt Containing Folic Acid and Iodine Among Ethiopian Women of Reproductive Age - a Household-randomized, Controlled, Community-based Trial

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.

Read the detailed description

Potentially eligible women of reproductive age (WRA) in two rural and two semi-urban communities (kebeles) in the Oromia Region of Ethiopia will be identified from existing census records. A convenience sample of 360 eligible, consenting women will be recruited following an initial screening interview at the women's homes. Before the screening interview, the data collector will read a disclosure statement concerning the purpose and the contents of the interview, and the data collector will then request verbal consent to obtain descriptive information on the women's age, general health status, pregnancy status, use of contraceptives, address, cell phone number (if available), and potential willingness to participate in the subsequent intervention trial.

After reviewing the women's health history and pregnancy status, measured blood pressure, and current use of contraceptives, the data collector will determine the women's potential eligibility for the trial. The data collector will describe the purposes of the trial, the study procedures and related risks and benefits, the confidentiality of results, and the fact that participation is voluntary. Women who are interested in participating in the study will be encouraged to ask any questions to the research team and consult with family members before providing their signed consent (in the presence of a neutral witness) to participate in the trial. Additional questions then will be asked of consenting women regarding their marital status, ethnicity, religion, educational level, and employment; and their housing characteristics (housing construction, water source, sanitary facilities, access to electricity and cell phone service), and selected household (HH) assets; and the women will be invited to attend the local health facility to complete additional interviews to assess their birth history, household food insecurity, and additional eligibility criteria, including anthropometrics, a pregnancy test, and fasting blood collection for anemia screening and other baseline measurements. Eligible, consenting women then will be randomly assigned to one of three study arms using a block randomization procedure with block size of six. The fasting blood samples obtained for anemia screening will also be used for measurement of red blood cell and serum folate, unmetabolized folic acid, homocysteine, vitamin B12, holo-transcobalamin, methyl malonic acid, other B vitamins, genetic polymorphisms that affect folate metabolism, thyroglobulin, glucose, insulin, retinol binding protein (RBP), ferritin, soluble transferrin receptor, C-reactive protein, and alpha-1 acid glycoprotein, and a malaria rapid diagnostic test (RDT).

Following enrollment, the study participants will be scheduled for a 24-hour urine collection to measure baseline sodium and iodine excretion, after which they will begin receiving the assigned study salt every two weeks. The women will be counseled to use the study salt for all food preparation and seasoning for a total of 26 weeks. Additional data collection during the course of the intervention will include: one or two full-day observed food records to measure discretionary salt intake and folate intake; one or two repeat 24-hour urine collections to measure sodium and iodine excretion; and bi-weekly home assessments of salt acceptability, continued contraceptive use, and any adverse events. At the time of these bi-weekly home visits, unused salt will be collected and a new allotment of salt will be delivered. Fasting blood samples will be collected again at a randomly assigned intermediate time point and at end line.

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Being tested
Iodized salt, Experimental: Iodized salt with lower-dose folic acid fortification, Experimental: Iodized salt with higher-dose folic acid fortification
Keywords
Salt fortification, Ethiopia
Medical subject headings
Folic Acid Deficiency, Anemia, Macrocytic, Vitamin B 12 Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iodized saltDietary 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.

  • Experimental: Iodized salt with lower-dose folic acid fortificationDietary 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.

  • Experimental: Iodized salt with higher-dose folic acid fortificationDietary 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.

Study groups in NCT06223854
Study groupRoleWhat they receive
Iodized saltActive comparatorRefined iodized salt containing 35 ppm iodine as potassium iodate
Receives: Dietary Supplement: Iodized salt
Iodized salt with lower-dose folic acid fortificationExperimentalRefined 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)
Receives: Dietary Supplement: Experimental: Iodized salt with lower-dose folic acid fortification
Iodized salt with higher-dose folic acid fortificationExperimentalRefined 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)
Receives: Dietary Supplement: Experimental: Iodized salt with higher-dose folic acid fortification

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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.

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

  4. 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.

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

  5. 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.

    Measured: Before and during the intervention

  6. 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.

    Measured: Throughout the course of the intervention, total of 26 weeks

Secondary outcomes (9)
  1. Hemoglobin concentration

    Hemoglobin concentration in venous blood will be measured at three time points, using an automated hematology analyzer.

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

  2. Serum B12

    Serum concentration of cyanocobalamin will be measured at three time points.

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

  3. Serum transcobalamin

    Serum concentration of transcobalamin will be measured at three time points.

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

  4. Serum methyl malonic acid

    Serum concentration of methyl malonic acid will be measured at three time points.

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

  5. Serum unmetabolized folic acid

    Unmetabolized folic acid will be measured in serum at three time points.

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

  6. Serum glucose

    Fasting serum glucose concentration will be measured at three time points.

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

  7. Serum insulin

    Fasting serum insulin concentration will be measured at three time points.

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

  8. Discretionary salt intake

    Discretionary salt intake will be measured by full-day, in-home weighed dietary records at one or two time points after the start of the intervention

    Measured: After the start of the intervention, between 4-20 weeks

  9. Urinary sodium excretion

    24-hour urinary sodium 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.

    Measured: Before and between 4-20 weeks after the start of the intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jan 2024
  2. Study start25 Apr 2024
  3. Primary completion16 Dec 2024
  4. Study completion16 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
360 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06223854
Sponsor's protocol ID
2078626
Acronym
DFS-IoFA-2
Status last verified
Jan 2025
First submitted
3 Jan 2024
Last updated
13 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Two years after completion of the data collection, the individual participant data (IPD) data sets will become publicly available to other investigators who have specific research questions that can be addressed by the data and that are not already under analysis by the core research team. Researchers who desire to have access to the clinical specimens will be requested to apply for the specimens and to describe the research question(s) they plan to address.

Publications

  • 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.

    PubMed 39477275
  • Pfeiffer CM, Fazili Z, Arnold CD, Woldeyohannes M, Nane D, Fereja M, Tessema M, Agbemafle I, Martinez H, McDonald CM, Brown KH. Serum Folate Forms Show Dose-Dependent Increases in Nonpregnant Ethiopian Women of Reproductive Age Participating in a Randomized Controlled Trial with Double-Fortified Salt Containing Iodine and Folic Acid. Curr Dev Nutr. 2026 Jun 15;10(7):109398. doi: 10.1016/j.cdnut.2026.109398. eCollection 2026 Jul.

    PubMed 42437195
  • Nane D, Fereja M, Agbemafle I, Arnold CD, Woldeyohannes M, McDonald CM, Tessema M, Martinez H, Brown KH. Provision of Salt at No Cost Does Not Affect Total Discretionary Salt Intakes among Adult Females in Ethiopia: Secondary Analysis of a Community-Based Intervention Trial. Curr Dev Nutr. 2026 May 6;10(6):107710. doi: 10.1016/j.cdnut.2026.107710. eCollection 2026 Jun.

    PubMed 42253364
  • 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 nonpregnant adult Ethiopian females and does not impair their iodine status: a community-based, household-randomized, dose-response trial. Am J Clin Nutr. 2026 Mar;123(3):101204. doi: 10.1016/j.ajcnut.2026.101204. Epub 2026 Jan 27.

    PubMed 41611087

Questions about this trial

What is this clinical trial studying?

A study testing Iodized salt, Experimental: Iodized salt with lower-dose folic acid fortification and Experimental: Iodized salt with higher-dose folic acid fortification in people with Folate Deficiency and Iodine Deficiency, run by University of California, Davis at 1 site in Ethiopia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Ethiopia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Red blood cell folate (time frame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06223854, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.

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