Clinical trial NCT05178407: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin A Deficiency
Iron-deficiency
Folate Deficiency
Vitamin B 12 Deficiency
Zinc Deficiency
Anemia
Keywords: Micronutrient, Food Fortification,
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: University of Ghana
name: Newcastle University
name: Penn State University
name: Helen Keller International
First posted: 2022-01-05
Enrollment: 2372
Sex: ALL
Minimum age (years): 2
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change in vitamin A status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in vitamin A status among children 2-5 years
timeFrame: 38 weeks
measure: Change in vitamin A status among lactating women 4-18 mo postpartum
timeFrame: 12 weeks
measure: Change in iron status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in iron status among children 2-5 years
timeFrame: 38 weeks
measure: Change in hemoglobin concentration among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in hemoglobin concentration among children 2-5 years
timeFrame: 38 weeks
measure: Change in zinc status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in zinc status among children 2-5 years
timeFrame: 38 weeks
measure: Change in folate status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in folate status among children 2-5 years
timeFrame: 38 weeks
measure: Change in vitamin B12 status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in vitamin B12 status among children 2-5 years
timeFrame: 38 weeks
measure: Change in vitamin B12 status among lactating women 4-18 months postpartum
timeFrame: 12 weeks
Secondary outcomes:
measure: Average daily household consumption of bouillon
timeFrame: 38 weeks
measure: Adherence to study-provided bouillon
timeFrame: 38 weeks
measure: Change in vitamin A status markers among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in serum folate concentration among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in plasma retinol concentration among children 2-5 years
timeFrame: 38 weeks
measure: Change in iodine status among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in iodine status among children 2-5 years
timeFrame: 38 weeks
measure: Change in iodine status among lactating women 4-18 months postpartum
timeFrame: 12 weeks
measure: Change in urinary sodium concentrations among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in inflammation among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in inflammation among children 2-5 years
timeFrame: 38 weeks
measure: Change in current or recent malaria among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in current or recent malaria among children 2-5 years
timeFrame: 38 weeks
measure: Morbidity among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Morbidity among children 2-5 years
timeFrame: 38 weeks
measure: Morbidity among lactating women 4-18 months postpartum
timeFrame: 12 weeks
measure: Change in dietary intake among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in dietary intake among children 2-5 years
timeFrame: 38 weeks
measure: Dietary intake among lactating women 4-18 months postpartum
timeFrame: 4 weeks
measure: Change in anemia among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in anemia among children 2-5 years
timeFrame: 38 weeks
measure: Change in micronutrient deficiency among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in micronutrient deficiency among children 2-5 years
timeFrame: 38 weeks
measure: Change in low milk nutrient concentrations among lactating women 4-18 months postpartum
timeFrame: 12 weeks
measure: Systolic and diastolic blood pressure among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Hypertension among non-pregnant, non-lactating women
timeFrame: 38 weeks
measure: Change in faecal calprotectin concentrations among children 2-5 years
timeFrame: 38 weeks
measure: Change in height-for-age Z score and stunting (HAZ < -2) among children 2-5 years
timeFrame: 38 weeks
measure: Change in weight-for-height Z score and wasting (WHZ < -2) among children 2-5 years
timeFrame: 38 weeks
measure: Change in cognitive development among children 2-5 years
timeFrame: 38 weeks
measure: Fecal microbiota among children 2-5 years
timeFrame: 38 weeks
measure: Change in cognitive development among children 2-5 years
timeFrame: 38 weeks
Other outcomes:
measure: Household food security
timeFrame: 38 weeks
measure: Household water security
timeFrame: 38 weeks
measure: Change in weight-for-age Z score and underweight (WAZ < -2) among children 2-5 years
timeFrame: 38 weeks
measure: Change in zinc protoporphyrin (ZPP) concentrations
timeFrame: 38 weeks
Locations:
city: Accra
country: Ghana
facility: University of Ghana
Study officials:
affiliation: Department of Nutrition, UC Davis
name: Reina Engle-Stone, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ghana
name: Seth Adu-Afarwuah, PhD
role: PRINCIPAL_INVESTIGATOR
References: