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

Iodine Deficiency Clinical Trial

— DFS-IoFA-2  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06223854
• Other study ID #: 2078626-1
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 25, 2024
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2024
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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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Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 360
• Est. completion date: September 30, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 49 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Anemia
• Anemia Deficiency
• Folate Deficiency
• Folic Acid Deficiency
• Iodine Deficiency
• Salt Intake
• Vitamin B 12 Deficiency

Intervention

Dietary Supplement:
• Iodized salt
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 fortification
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 fortification
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.

Locations

Country	Name	City	State
Ethiopia	Ethiopian Public Health Institute	Addis Ababa

Sponsors (5)

Lead Sponsor	Collaborator
University of California, Davis	Ethiopian Public Health Institute, Nutrition International, University of California, San Francisco, University of Rhode Island

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Blood pressure	Resting systolic and diastolic blood pressure will be measured at baseline and at the time of subsequent blood drawings.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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
Primary	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	Hemoglobin concentration	Hemoglobin concentration in venous blood will be measured at three time points, using an automated hematology analyzer.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum B12	Serum concentration of cyanocobalamin will be measured at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum transcobalamin	Serum concentration of transcobalamin will be measured at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum methyl malonic acid	Serum concentration of methyl malonic acid will be measured at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum unmetabolized folic acid	Unmetabolized folic acid will be measured in serum at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum glucose	Fasting serum glucose concentration will be measured at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	Serum insulin	Fasting serum insulin concentration will be measured at three time points.	Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Secondary	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	After the start of the intervention, between 4-20 weeks
Secondary	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.	Before and between 4-20 weeks after the start of the intervention