Clinical trial NCT06100146: Effectiveness of Fortification With Folic Acid and Vitamin B12 Among Teenage Girls
Official title: Does Small Scale Cereal-based Fortification Hold the Key to Improved Micronutrient Status in Ethiopia? The Case of Folic Acid and Vitamin B12 in Teenage Girls in Arba Minch, Ethiopia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Folate Deficiency
Vitamin B 12 Deficiency
Anemia, Megaloblastic
Cognitive Development
Depressive Symptoms
Keywords: Small scale fortification
Folic acid
Vitamin B12
Anemia
Cognitive development
Teenage girls
Lead sponsor: University Ghent
Sponsor class: OTHER
Collaborators: name: Arba Minch University
name: Institut de Recherche en Sciences de la Sante, Burkina Faso
name: Addis Ababa University
First posted: 2023-10-25
Enrollment: 474
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In randomized control trial, eligible teenage girls attending one of the schools in AM-HDSS will be randomly assigned to:

1. An intervention group receiving a standard bag of cereal flours fortified with folic acid and Vitamin B12 at local mills every week for six months.
2. A placebo group receiving a standard bag of unfortified cereal flours every week for six months.

Participants in all the treatment groups remain eligible to benefit from the standard health care and nutrition programs provided at school, such as deworming at the beginning of the school year.
Primary purpose: PREVENTION

Brief summary: Folic acid and vitamin B12 play an interdependent role in key cellular processes, namely deoxyribonucleic acid synthesis, cell division, red blood cell formation, and nervous system myelination. A deficiency of either vitamin will predispose teenagers to many diseases, which persist across their lifespan. Fortification of food with micronutrients has been promoted to reduce micronutrient deficiencies. A large segment of vulnerable populations in low- and middle-income countries (LMICs) resides in rural settings and has limited access to large-scale commercialized fortified foods. In such operational constraints, the use of locally (small-scale) fortified cereals could be an alternative intervention. The study aims to evaluate the effectiveness of small scale folic acid and vitamin B12 fortified cereals in improving folate and vitamin B12 status, growth velocity, puberty status, anaemia, cognitive development and mental health among teenage girls, in rural rift valley of Ethiopia.

Detailed description: Folic acid (FA) and vitamin B12 play an interdependent role in key cellular processes, namely deoxyribonucleic acid synthesis, cell division, red blood cell formation, and nervous system myelination. Teenagers are the future mothers. Hence their health and nutritional status have long term consequences on future pregnancies and birth outcomes. Neural Tube Defects (NTDs) are a group of fatal or severely disabling birth defects known to be mainly a consequence of severe folate deficiency in early pregnancy. The policy of advising women to take iron \& FA (IFA) supplements during pregnancy has not been successful in preventing NTDs because of the low adherence to antenatal care services including IFA, the large proportion of unplanned pregnancies, the timing at which IFA supplementation starts, and the logistical limitation that makes the access to IFA limited. The evidence is strong on the importance of food fortification in the promotion of maternal and child health mainly through reducing micronutrient deficiencies. A large segment of vulnerable populations in developing countries resides in rural settings and has limited access to fortified foods in the market. In such operational constraints, using locally fortified cereals could be an alternative intervention. However, there is a paucity of evidence regarding effectiveness of small-scale cereal-based fortification; in Ethiopia, the evidence is inexistent. Moreover, teenage girls are an under-studied group and do not constitute a target population from different nutritional intervention programs.

The overall objective of this study is to evaluate the effectiveness of small-scale folic acid and vitamin B12-fortified cereals in improving folate and vitamin B12 status, growth velocity, puberty status, anaemia, cognitive development and mental health among rural teenage girls (13-19 years of age).

This study will be conducted in Arba Minch Health and Demographic Surveillance Sites (AM-HDSS), Southern Ethiopia from October 2023 to April 2024. Effectiveness of intake of folic acid and vitamin B12 fortified meals will be evaluated in a randomized, double-blind controlled trial among 474 teenage girls between 13 and 19 years of age who are residing in and attending one of the schools at AM-HDSS.

Data on the following variables, except for demographic characteristics of teenage girls and their respective parents and/or household heads will be collected at the start and end point of the 6 months intervention. Data collection will be carried out at schools and at respective girls' home.

* Demographic characteristics of the teenage girls, morbidity status, helminthic infections, dietary intake, anthropometry, puberty status, presence of depressive symptoms, biochemical samples and cognitive development will be assessed in teenage girls directly at schools.
* Socio-demographic characteristics of the parents or the head of the household if different from parents, family wealth status, food security, health care services and environmental characteristics will be collected in recruited teenage girls' households within the one week following the enrolment and at the end of the intervention.

Eligibility criteria: Inclusion Criteria:

Teenage girls between 13 and 19 years of age who live in households at Arba Minch Health and Demographic Surveillance Sites (AM-HDSS) are eligible to participate in the study if:

* One or both of their parents signed an informed consent form and the girl's agreement.
* Their parents and the girl planned to stay in the study area during the period of the study (minimum 6 months) in the kebele.
* Both parents and girls accept the intervention packages including blood draws and home visits.

Exclusion Criteria:

* Chronically ill girls diagnosed with diabetes and asthma;
* Severely undernourished girls (defined as body mass index z score \< -3 standard deviations of the median World Health Organization reference population);
* Severely anaemic girls (Hb concentration \<80g/L);
* Teenage girls who are pregnant, lactating or taking IFA/B12 supplements;
* Diagnosed hemoglobinopathy (sickle cell or thalassemia);
* Diagnosed liver diseases like acute hepatitis, cirrhosis, hepatocellular carcinoma, and metastatic liver disease

Primary outcomes:
measure: Serum folic acid concentrations
timeFrame: Assessed at 6 months
measure: Erythrocyte (RBC) folic acid concentrations
timeFrame: Assessed at 6 months
measure: General cognitive ability
timeFrame: Assessed at 6 months
measure: Working memory
timeFrame: Assessed at 6 months
measure: Depression
timeFrame: Assessed at 6 months
measure: Serum vitamin B12 concentrations
timeFrame: Assessed at 6 months
measure: Fat-free mass
timeFrame: Assessed at 6 months
measure: Fat mass
timeFrame: Assessed at 6 months
Secondary outcomes:
measure: RBC structure (megaloblastic anaemia)
timeFrame: Assessed at 6 months
measure: Plasma homocysteine concentrations
timeFrame: Assessed at 6 months
measure: Weight
timeFrame: Assessed at 3 and 6 months
measure: Adherence to the intervention/fortification
timeFrame: Assessed weekly for the whole period of intervention (until 6 months)
measure: Haemoglobin concentration
timeFrame: Assessed at 6 months
measure: Height
timeFrame: Assessed at 6 months
measure: Puberty status
timeFrame: Assessed at 6 months of fortification
measure: Prevalence of soil-transmitted helminths
timeFrame: Assessed at 6 months
measure: Prevalence of Schistosome infection
timeFrame: Assessed at 6 months
Other outcomes:
Locations:
city: Arba Minch
country: Ethiopia
facility: Arba Minch Health and Demographic Surveillance System sites
city: Arba Minch
country: Ethiopia
facility: Arba Minch University
Study officials:
affiliation: University Ghent
name: Stefaan De Henauw, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Mildon A, Klaas N, O'Leary M, Yiannakis M. Can fortification be implemented in rural African communities where micronutrient deficiencies are greatest? Lessons from projects in Malawi, Tanzania, and Senegal. Food Nutr Bull. 2015 Mar;36(1):3-13. doi: 10.1177/156482651503600101.