Clinical trial NCT06223854: Acceptability and Nutritional Impact of Double-fortified Salt Containing Iodine and Folic Acid
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Folate Deficiency
Iodine Deficiency
Anemia Macrocytic
Anemia Deficiency
Salt Intake
Vitamin B 12 Deficiency
Keywords: Salt fortification
Ethiopia
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Ethiopian Public Health Institute
name: University of California, San Francisco
name: University of Rhode Island
name: Nutrition International
First posted: 2024-01-25
Enrollment: 360
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: PREVENTION

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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Eligibility criteria: 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

Primary outcomes:
measure: Red blood cell folate
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum folate
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum homocysteine
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum thyroglobulin
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: 24-hour urinary iodine excretion
timeFrame: Before and during the intervention
measure: Serious adverse events
timeFrame: Throughout the course of the intervention, total of 26 weeks
Secondary outcomes:
measure: Hemoglobin concentration
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum B12
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum transcobalamin
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum methyl malonic acid
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum unmetabolized folic acid
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum glucose
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Serum insulin
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
measure: Discretionary salt intake
timeFrame: After the start of the intervention, between 4-20 weeks
measure: Urinary sodium excretion
timeFrame: Before and between 4-20 weeks after the start of the intervention
Other outcomes:
measure: Blood pressure
timeFrame: Baseline (pre-intervention), intermediate time point (between 4-20 weeks), and end line (24-26 weeks)
Locations:
city: Addis Ababa
country: Ethiopia
facility: Ethiopian Public Health Institute
Study officials:
affiliation: UC Davis
name: KENNETH H BROWN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ethiopian Public Health Institute
name: Masresha Tessema, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.