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

Not Applicable
Completed
Conditions
Iodine Deficiency
Vitamin B 12 Deficiency
Folate Deficiency
Anemia Deficiency
Anemia Macrocytic
Salt Intake
Interventions
Dietary Supplement: Iodized salt
Registration Number
NCT06223854
Lead Sponsor
University of California, Davis
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.

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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Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
360
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Iodized saltIodized saltRefined iodized salt containing 35 ppm iodine as potassium iodate
Primary Outcome Measures
NameTimeMethod
Serious adverse eventsThroughout the course of the intervention, total of 26 weeks

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.

Red blood cell folateBaseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

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.

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

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.

24-hour urinary iodine excretionBefore and during the intervention

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.

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

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.

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

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.

Secondary Outcome Measures
NameTimeMethod
Hemoglobin concentrationBaseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

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

Serum methyl malonic acidBaseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

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

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

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

Urinary sodium excretionBefore and between 4-20 weeks after the start of the intervention

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.

Serum B12Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

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

Discretionary salt intakeAfter the start of the intervention, between 4-20 weeks

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

Serum unmetabolized folic acidBaseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)

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

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

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

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

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

Trial Locations

Locations (1)

Ethiopian Public Health Institute

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Addis Ababa, Ethiopia

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