Effect of Household Use of Multiple Micronutrient-fortified Bouillon on Micronutrient Status Among Women and Children in Two Districts in the Northern Region of Ghana

Anemia Clinical Trial

Official title:

Effect of Household Use of Multiple Micronutrient-fortified Bouillon on Micronutrient Status Among Women and Children in Two Districts in the Northern Region of Ghana

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05178407
• Other study ID #: 1837253
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 16, 2023
• Est. completion date: June 2024

Study information

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

Clinical Trial Summary

Background: Micronutrient (MN) deficiencies are severe and widespread in West Africa, particularly among young children and women of reproductive age. Bouillon is a promising food fortification vehicle because the product is centrally processed on large scale, consumed by most households in West African countries (even rural, poor households), and consumed by most members of the household in relatively constant amounts. However, several important research questions remain regarding whether the use of fortified bouillon would be feasible and effective for preventing or reducing micronutrient deficiencies in communities where such deficiencies are common. Specifically, no studies have assessed the impacts of multiple micronutrient-fortified bouillon on micronutrient status. The West Africa Condiment Micronutrient Innovation Trial (CoMIT) Project aims to address this gap, to inform future discussions around fortification of bouillon cubes and related products.

Objective: This study aims to assess the impacts of household use of multiple micronutrient-fortified bouillon cubes (containing iodine in addition to vitamin A, folic acid, vitamin B12, iron, and zinc), compared to control bouillon cubes fortified with iodine only, on:

1. Micronutrient status among women 15-49 years of age and children 2-5 years of age after 9 months of intervention

2. Hemoglobin concentrations among women 15-49 years of age and children 2-5 years of age after 9 months of intervention

3. Breast milk micronutrient concentrations among lactating women 4-18 months postpartum after 3 months of intervention

Methods: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate that deficiencies in the selected nutrients are common. Potential participants will be: 1) non-pregnant non-lactating women of reproductive age (15 - 49 years old), 2) children 2-5 years of age, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes:

1. a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or

2. a control cube containing iodine only

Each participant's household will receive a specific amount of bouillon cube every 2 weeks, and households will be advised to prepare their meals as usual, using the study-provided cubes. The trial duration will be 9 months (38 weeks) for non-pregnant, non-lactating women and children 2-5 years of age, and 3 months (12 weeks) for lactating women. The primary outcomes will be changes from baseline to endline in concentrations of haemoglobin and biomarkers of micronutrient status. Secondary outcomes will include change in prevalence of anaemia and micronutrient deficiency; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and children's anthropometric measures and child development.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 2372
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 49 Years

Eligibility

Inclusion/exclusion criteria at recruitment (home visit):

Household

Inclusion criteria:

• Head of household provides oral consent for the participation of household members (index participants), and willingness to have study-provided bouillon cubes used in their household for the next 10 months.

Exclusion criteria:

• Reported chronic medical condition requiring frequent blood transfusion (e.g. severe forms of thalassemia) among any household members;

• Current participation of any household member in a clinical trial;

• Reported shrimp, wheat, milk, soy, eggs, celery, fish, or mollusk allergy, or a previous adverse reaction to bouillon by the participant or any member of their household.

Non-pregnant, non-lactating women of reproductive age

Inclusion criteria:

• Non-pregnant non-lactating women of reproductive age (15 - 49 years);

• Signed the informed consent form (or in the case of adolescents 15-17 years of age, unmarried and still living with their parents, assent provided from the index participant and consent from a parent or guardian) ;

• Planning to remain in the study area for the next 10 months;

• Willing to use study-provided bouillon in household cooking for the next 10 months;

• Not planning to become pregnant during the next 10 months.

Exclusion criteria:

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Chronic severe medical condition (e.g. malignancy) or congenital anomalies requiring frequent medical attention or potentially interfering with nutritional status;

• Unable to provide informed consent due to impaired decision-making abilities.

Children 2-5 years of age (24-59 mo)

Inclusion criteria:

• Child 2-5 years of age (24-59 mo);

• Signed informed consent for the child's participation from a parent or guardian;

• Planning to remain in the study area for the next 10 months;

• Caregiver willing to use study-provided bouillon in household cooking for the next 10 months.

Exclusion criteria:

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever, [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Mid-upper arm circumference < 11.5 cm;

• Chronic severe medical condition (e.g. malignancy) or congenital anomalies requiring frequent medical attention or potentially interfering with nutritional status.

Lactating women

Inclusion criteria:

• Non-pregnant women of reproductive age (15 - 49 years), currently breastfeeding a child who is 4-18 months of age;

• Signed the informed consent form (or in the case of adolescents 15-17 years of age, unmarried and still living with their parents, provide assent from the index participant and consent from a parent or guardian);

• Planning to remain in the study area for the next 4 months;

• Planning to breastfeed for the next 4 months;

• Willing to use study-provided bouillon in household cooking for the next 4 months;

• Not planning to become pregnant during the next 4 months.

Exclusion criteria:

• Pregnancy (determined by self-report);

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever[temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Chronic severe medical condition (e.g. malignancy) or congenital anomalies requiring frequent medical attention or potentially interfering with nutritional status;

• Unable to provide informed consent due to impaired decision-making abilities.

Exclusion criteria at screening visit for vitamin A isotope dose (WRA only):

Non-pregnant, non-lactating women of reproductive age

• Hemoglobin < 80 g/L at baseline screening visit;

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Recent diarrhea [=3 liquid or semiliquid stools in 72 hours]) [individual may repeat eligibility assessment after deferral];

• Reported consumption of vitamin A-rich foods (e.g., liver) in the previous 24 hours [individual may repeat eligibility assessment after deferral];

• Pregnancy (as ascertained via urine pregnancy test for human chorionic gonadotropin on the day of isotope dosing);

• Incomplete consumption of vitamin A isotope dose;

• Positive malaria RDT on the day of isotope dosing [individual may repeat eligibility assessment after deferral];

• CRP > 5 mg/L on the day of isotope dosing [individual may repeat eligibility assessment after deferral].

Exclusion criteria at baseline visit:

Non-pregnant, non-lactating women of reproductive age

• Hemoglobin < 80 g/L;

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Pregnancy (determined by self-report).

Children 2-5 years of age

• Hemoglobin < 70 g/L;

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, loss of smell or taste within the past 72 hours) [individual may repeat eligibility assessment after referral];

• Severe acute malnutrition at baseline (weight-for-height Z-score < -3 SD or bilateral oedema).

Lactating women

• Severe illness warranting immediate hospital referral;

• COVID-19 diagnosis or exposure in the previous two weeks [individual may repeat eligibility assessment after deferral];

• Presence of morbidity symptoms suggesting COVID-19 infection (fever [temperature > 38°C], chills/shaking, dry cough, shortness of breath or difficulty breathing, or loss of taste or smell within the past 72 hours) [individual may repeat eligibility assessment after deferral];

• Pregnancy (determined by self-report);

• Cessation of lactation, or planning to discontinue breastfeeding in the next three months.

Exclusion criteria during course of the intervention:

Non-pregnant, non-lactating women of reproductive age

• Pregnancy (determined by self-report);

• Pregnancy (as ascertained via urine pregnancy test for human chorionic gonadotropin at pre-endline isotope dosing).

Lactating women

• Cessation of lactation (determined by self-report);

• Pregnancy (determined by self-report).

Related Conditions & MeSH terms

• Anemia
• Folate Deficiency
• Folic Acid Deficiency
• Iron-deficiency
• Night Blindness
• Vitamin A Deficiency
• Vitamin B 12 Deficiency
• Zinc Deficiency

Intervention

Dietary Supplement:
• Multiple micronutrient-fortified bouillon cube
Bouillon cube fortified with 80 µg/g folic acid, 1.2 µg/g Vitamin B12, 3 mg/g Zinc (ZnO), 4 mg/g Iron (FePP/citric acid/trisodium citrate), 200 µg/g Vitamin A (retinyl palmitate), 30 µg/g Iodine (KIO3)
• Control bouillon cube (iodine-only)
Bouillon cube fortified with 30 µg/g Iodine (KIO3)

Locations

Country	Name	City	State
Ghana	University of Ghana	Accra

Sponsors (5)

Lead Sponsor	Collaborator
University of California, Davis	Helen Keller International, Newcastle University, Penn State University, University of Ghana

Country where clinical trial is conducted

Ghana, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Household food security	Assessed monthly using the Household Food Insecurity and Access Scale (HFIAS)	38 weeks
Other	Household water security	Assessed monthly by the Household Water Insecurity Experience Scale (HWISE)	38 weeks
Other	Change in weight-for-age Z score and underweight (WAZ < -2) among children 2-5 years	Standardized using WHO child growth standards	38 weeks
Other	Change in zinc protoporphyrin (ZPP) concentrations	Measured by portable device	38 weeks
Primary	Change in vitamin A status among non-pregnant, non-lactating women	Total body vitamin A stores and estimated liver vitamin A concentration measured by retinol isotope dilution at baseline and endline	38 weeks
Primary	Change in vitamin A status among children 2-5 years	Plasma retinol-binding protein (RBP) concentrations, measured at baseline and endline	38 weeks
Primary	Change in vitamin A status among lactating women 4-18 mo postpartum	Breast milk vitamin A concentration and vitamin A per gram fat, measured at baseline and endline	12 weeks
Primary	Change in iron status among non-pregnant, non-lactating women	Plasma ferritin and soluble transferrin receptor concentrations, and calculated total body iron stores (BIS), measured at baseline and endline	38 weeks
Primary	Change in iron status among children 2-5 years	Plasma ferritin and soluble transferrin receptor concentrations, and calculated total body iron stores (BIS), measured at baseline and endline	38 weeks
Primary	Change in hemoglobin concentration among non-pregnant, non-lactating women	Hemoglobin concentration measured in venous blood at baseline and endline	38 weeks
Primary	Change in hemoglobin concentration among children 2-5 years	Hemoglobin concentration measured in venous blood at baseline and endline	38 weeks
Primary	Change in zinc status among non-pregnant, non-lactating women	Plasma zinc measured at baseline and endline	38 weeks
Primary	Change in zinc status among children 2-5 years	Plasma zinc measured at baseline and endline	38 weeks
Primary	Change in folate status among non-pregnant, non-lactating women	Erythrocyte folate concentrations, calculated from whole blood folate and serum folate concentrations, measured at baseline and endline	38 weeks
Primary	Change in folate status among children 2-5 years	Plasma folate concentrations, measured at baseline and endline	38 weeks
Primary	Change in vitamin B12 status among non-pregnant, non-lactating women	Plasma vitamin B12 concentrations, measured at baseline and endline	38 weeks
Primary	Change in vitamin B12 status among children 2-5 years	Plasma vitamin B12 concentrations, measured at baseline and endline	38 weeks
Primary	Change in vitamin B12 status among lactating women 4-18 months postpartum	Breast milk vitamin B12 concentrations, measured at baseline and endline	12 weeks
Secondary	Average daily household consumption of bouillon	Assessed biweekly by questionnaire, observed stocks, and wrapper counts.	38 weeks
Secondary	Adherence to study-provided bouillon	Consumption of study-provided bouillon cubes, expressed as percentage of all bouillon consumed by the household, and as percentage of study-provided consumed by the household, assessed biweekly by questionnaire, observed stocks, and wrapper counts	38 weeks
Secondary	Change in vitamin A status markers among non-pregnant, non-lactating women	Plasma or serum retinol and retinol-binding protein (RBP) concentrations, measured at baseline and endline	38 weeks
Secondary	Change in serum folate concentration among non-pregnant, non-lactating women	Serum folate concentration, measured at baseline and endline	38 weeks
Secondary	Change in plasma retinol concentration among children 2-5 years	Measured at baseline and endline	38 weeks
Secondary	Change in iodine status among non-pregnant, non-lactating women	Urinary iodine concentration, measured at baseline and endline	38 weeks
Secondary	Change in iodine status among children 2-5 years	Urinary iodine concentration, measured at baseline and endline	38 weeks
Secondary	Change in iodine status among lactating women 4-18 months postpartum	Urinary iodine concentration, measured at baseline and endline	12 weeks
Secondary	Change in urinary sodium concentrations among non-pregnant, non-lactating women	Urinary sodium concentration, expressed as sodium:potassium ratio, measured at baseline and endline	38 weeks
Secondary	Change in inflammation among non-pregnant, non-lactating women	Plasma concentrations of acute phase proteins, measured at baseline and endline	38 weeks
Secondary	Change in inflammation among children 2-5 years	Plasma concentrations of acute phase proteins, measured at baseline and endline	38 weeks
Secondary	Change in current or recent malaria among non-pregnant, non-lactating women	Assessed by rapid diagnostic test at baseline and endline	38 weeks
Secondary	Change in current or recent malaria among children 2-5 years	Assessed by rapid diagnostic test at baseline and endline	38 weeks
Secondary	Morbidity among non-pregnant, non-lactating women	Cumulative days of symptoms over the study period, assessed by questionnaires administered biweekly	38 weeks
Secondary	Morbidity among children 2-5 years	Cumulative days of symptoms over the study period, assessed by questionnaires administered biweekly	38 weeks
Secondary	Morbidity among lactating women 4-18 months postpartum	Cumulative days of symptoms over the study period, assessed by questionnaires administered biweekly	12 weeks
Secondary	Change in dietary intake among non-pregnant, non-lactating women	Dietary intake of bouillon, salt, fortifiable foods, energy, macronutrients, and micronutrients, assessed by repeated 24-hour dietary recalls at baseline and endline	38 weeks
Secondary	Change in dietary intake among children 2-5 years	Dietary intake of bouillon, salt, fortifiable foods, energy, macronutrients, and micronutrients, assessed by repeated 24-hour dietary recalls at baseline and endline	38 weeks
Secondary	Dietary intake among lactating women 4-18 months postpartum	Dietary intake of bouillon, salt, fortifiable foods, energy, macronutrients, and micronutrients, assessed by repeated 24-hour dietary recalls at baseline	4 weeks
Secondary	Change in anemia among non-pregnant, non-lactating women	Hemoglobin concentrations < 12 g/dL, measured at baseline and endline	38 weeks
Secondary	Change in anemia among children 2-5 years	Hemoglobin concentrations < 11 g/dL, measured at baseline and endline	38 weeks
Secondary	Change in micronutrient deficiency among non-pregnant, non-lactating women	Based on biomarkers of micronutrient status (vitamin A, iron, zinc, folate, vitamin B12), measured at baseline and endline	38 weeks
Secondary	Change in micronutrient deficiency among children 2-5 years	Based on biomarkers of micronutrient status (vitamin A, iron, zinc, folate, vitamin B12), measured at baseline and endline	38 weeks
Secondary	Change in low milk nutrient concentrations among lactating women 4-18 months postpartum	Based on concentrations of vitamin A and vitamin B12, measured at baseline and endline	12 weeks
Secondary	Systolic and diastolic blood pressure among non-pregnant, non-lactating women	Assessed by portable device	38 weeks
Secondary	Hypertension among non-pregnant, non-lactating women	Based on blood pressure measured by portable device	38 weeks
Secondary	Change in faecal calprotectin concentrations among children 2-5 years	Stool samples collected at baseline and endline	38 weeks
Secondary	Change in height-for-age Z score and stunting (HAZ < -2) among children 2-5 years	Standing height, standardized using WHO child growth standards	38 weeks
Secondary	Change in weight-for-height Z score and wasting (WHZ < -2) among children 2-5 years	Standardized using WHO child growth standards	38 weeks
Secondary	Change in cognitive development among children 2-5 years	Malawi Developmental Assessment Tool (MDAT) scores in 4 domains (gross motor, fine motor, language, social)	38 weeks
Secondary	Fecal microbiota among children 2-5 years	Stool samples collected at baseline and endline	38 weeks
Secondary	Change in cognitive development among children 2-5 years	Early Years Toolbox scores at baseline and endline	38 weeks