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Effectiveness of Fortification With Folic Acid and Vitamin B12 Among Teenage Girls

Primary Purpose

Folate Deficiency, Vitamin B 12 Deficiency, Anemia, Megaloblastic

Status
Not yet recruiting
Phase
Not Applicable
Locations
Ethiopia
Study Type
Interventional
Intervention
Folic acid and vitamin B12 fortified flour
Unfortified cereal flour
Sponsored by
University Ghent
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Folate Deficiency focused on measuring Small scale fortification, Folic acid, Vitamin B12, Anemia, Cognitive development, Teenage girls

Eligibility Criteria

13 Years - 19 Years (Child, Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Arba Minch University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Control group

folic acid & vit B12 fortified flour

Arm Description

Teenage girls randomly assigned to the control group will receive a standard bag of unfortified cereal flours every week for six months.

Teenage girls randomly assigned to the control group will receive a standard bag of cereal flours fortified with folic acid and Vit B12 every week for six months.

Outcomes

Primary Outcome Measures

Serum folic acid concentrations
Serum folate levels ng/ml (nmol/l)
Erythrocyte (RBC) folic acid concentrations
RBC folate level ng/ml (nmol/l)
General cognitive ability
Raven Progressive Matrices (RPM) tests, a measure of nonverbal intelligence.
Working memory
Digit Span (Forward, Backward, and Sequencing) is a standardized test that assesses the working memory of participants.
Depression
Depressive symptoms will be assessed by Patient Health Questionnaire (PHQ) 9 modified for adolescents (PHQ-9A), a self-report instrument comprised of 9-items. Items are rated on a four-point ordinal scale.
Serum vitamin B12 concentrations
Serum vitamin B12 level (pmol/L)
Fat-free mass
An index of adiposity will be measured to evaluate girls' body composition, in %
Fat mass
An index of adiposity will be measured to evaluate girls' body composition, in kg

Secondary Outcome Measures

RBC structure (megaloblastic anaemia)
Mean Corpuscular Volume (MCV) in femtoliters/fl
Plasma homocysteine concentrations
Plasma homocysteine level (µmol/L)
Weight
Participant weight (kg)
Adherence to the intervention/fortification
adherence to the flour consumption will be assessed through home to home visit in a weekly basis.
Haemoglobin concentration
Haemoglobin concentration (g/dl)
Height
Participant height (cm)
Puberty status
The pubertal status will be assessed by Pubertal Development Scale which has a 4-point scale ranging from 1 (has not begun) to 4 (development completed). Girls will report on their body hair development, growth spurt, skin changes, breast development and the occurrence of menarche (1=no and 4=yes).
Prevalence of soil-transmitted helminths
The presence of worm parasites and egg density in the stools. Three common parasites and their eggs will be investigated, i.e. Ascaris lumbricoides (round worm), Trichuris trichiura (whipworm) and Ancyclostoma duodenale or Necater americanus (hookworms)
Prevalence of Schistosome infection
The prevalence of Schistosoma mansoni infection

Full Information

First Posted
October 3, 2023
Last Updated
October 20, 2023
Sponsor
University Ghent
Collaborators
Arba Minch University, Institut de Recherche en Sciences de la Sante, Burkina Faso, Addis Ababa University
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1. Study Identification

Unique Protocol Identification Number
NCT06100146
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Ghent
Collaborators
Arba Minch University, Institut de Recherche en Sciences de la Sante, Burkina Faso, Addis Ababa University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
In randomized control trial, eligible teenage girls attending one of the schools in AM-HDSS will be randomly assigned to: 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. 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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Flours will be indistinguishable in appearance except for the vitamins added to the flours of the intervention group. An independent trained person will be assigned to monitor the fortification process and the two products will be packed immediately and coded.
Allocation
Randomized
Enrollment
474 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Teenage girls randomly assigned to the control group will receive a standard bag of unfortified cereal flours every week for six months.
Arm Title
folic acid & vit B12 fortified flour
Arm Type
Experimental
Arm Description
Teenage girls randomly assigned to the control group will receive a standard bag of cereal flours fortified with folic acid and Vit B12 every week for six months.
Intervention Type
Dietary Supplement
Intervention Name(s)
Folic acid and vitamin B12 fortified flour
Other Intervention Name(s)
Intervention group
Intervention Description
Standard bags of fortified cereal-based flours will be prepared at local mills from the common staple cereal food in the area. The dose of vitamins will be added to the flour of the intervention group and mixed with batch mixing technique. The concentration of folic acid and vitamin B12 per 1kg of flour will be 2mg and 0.02mg, respectively. Participants will be supplied with 6 kg bags of flour, which will be enough for 30 days, and 1.5kg bags of flour will be delivered to their home on a weekly basis and lasting for 6 months. Instructions on the preparation of meals and frequency of intake with a weekly compliance sheet will be provided for monitoring the intervention.
Intervention Type
Other
Intervention Name(s)
Unfortified cereal flour
Other Intervention Name(s)
Control group
Intervention Description
Standard bags of unfortified cereal-based flours will be prepared at local mills from the common staple cereal food in the area. Participants will be supplied with 6 kg bags of flour, which will be enough for 30 days, and 1.5kg bags of flour will be delivered to their home on a weekly basis and lasting for 6 months. Instructions on the preparation of meals and frequency of intake with a weekly compliance sheet will be provided for monitoring the intervention.
Primary Outcome Measure Information:
Title
Serum folic acid concentrations
Description
Serum folate levels ng/ml (nmol/l)
Time Frame
Assessed at 6 months
Title
Erythrocyte (RBC) folic acid concentrations
Description
RBC folate level ng/ml (nmol/l)
Time Frame
Assessed at 6 months
Title
General cognitive ability
Description
Raven Progressive Matrices (RPM) tests, a measure of nonverbal intelligence.
Time Frame
Assessed at 6 months
Title
Working memory
Description
Digit Span (Forward, Backward, and Sequencing) is a standardized test that assesses the working memory of participants.
Time Frame
Assessed at 6 months
Title
Depression
Description
Depressive symptoms will be assessed by Patient Health Questionnaire (PHQ) 9 modified for adolescents (PHQ-9A), a self-report instrument comprised of 9-items. Items are rated on a four-point ordinal scale.
Time Frame
Assessed at 6 months
Title
Serum vitamin B12 concentrations
Description
Serum vitamin B12 level (pmol/L)
Time Frame
Assessed at 6 months
Title
Fat-free mass
Description
An index of adiposity will be measured to evaluate girls' body composition, in %
Time Frame
Assessed at 6 months
Title
Fat mass
Description
An index of adiposity will be measured to evaluate girls' body composition, in kg
Time Frame
Assessed at 6 months
Secondary Outcome Measure Information:
Title
RBC structure (megaloblastic anaemia)
Description
Mean Corpuscular Volume (MCV) in femtoliters/fl
Time Frame
Assessed at 6 months
Title
Plasma homocysteine concentrations
Description
Plasma homocysteine level (µmol/L)
Time Frame
Assessed at 6 months
Title
Weight
Description
Participant weight (kg)
Time Frame
Assessed at 3 and 6 months
Title
Adherence to the intervention/fortification
Description
adherence to the flour consumption will be assessed through home to home visit in a weekly basis.
Time Frame
Assessed weekly for the whole period of intervention (until 6 months)
Title
Haemoglobin concentration
Description
Haemoglobin concentration (g/dl)
Time Frame
Assessed at 6 months
Title
Height
Description
Participant height (cm)
Time Frame
Assessed at 6 months
Title
Puberty status
Description
The pubertal status will be assessed by Pubertal Development Scale which has a 4-point scale ranging from 1 (has not begun) to 4 (development completed). Girls will report on their body hair development, growth spurt, skin changes, breast development and the occurrence of menarche (1=no and 4=yes).
Time Frame
Assessed at 6 months of fortification
Title
Prevalence of soil-transmitted helminths
Description
The presence of worm parasites and egg density in the stools. Three common parasites and their eggs will be investigated, i.e. Ascaris lumbricoides (round worm), Trichuris trichiura (whipworm) and Ancyclostoma duodenale or Necater americanus (hookworms)
Time Frame
Assessed at 6 months
Title
Prevalence of Schistosome infection
Description
The prevalence of Schistosoma mansoni infection
Time Frame
Assessed at 6 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Souheila Abbeddou, MSc, PHD
Phone
+32467630892
Email
Souheila.Abbeddou@UGent.be
First Name & Middle Initial & Last Name or Official Title & Degree
Eshetu Tariku, MPH
Phone
+251917835302
Email
eshetuzerihun.tariku@ugent.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stefaan De Henauw, MD,PHD
Organizational Affiliation
University of Ghent
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arba Minch University
City
Arba Minch
Country
Ethiopia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eshetu Tariku Zerihun, MPH
Email
EshetuZerihun.Tariku@UGent.be
First Name & Middle Initial & Last Name & Degree
Muluken Bekele Sorrie, MPH
Email
MulukenBekele.Sorrie@UGent.be
First Name & Middle Initial & Last Name & Degree
Jerome W Some, MD. PhD
First Name & Middle Initial & Last Name & Degree
Gudina Egata, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33083093
Citation
Oumer M, Taye M, Aragie H, Tazebew A. Prevalence of Spina Bifida among Newborns in Africa: A Systematic Review and Meta-Analysis. Scientifica (Cairo). 2020 Oct 6;2020:4273510. doi: 10.1155/2020/4273510. eCollection 2020.
Results Reference
background
PubMed Identifier
35942520
Citation
Wald NJ. Postscript to 'Folic acid and neural tube defects: Discovery, debate and the need for policy change'. J Med Screen. 2022 Sep;29(3):147. doi: 10.1177/09691413221117464. Epub 2022 Aug 8. No abstract available.
Results Reference
background
PubMed Identifier
23848243
Citation
Ardila A. Development of metacognitive and emotional executive functions in children. Appl Neuropsychol Child. 2013;2(2):82-7. doi: 10.1080/21622965.2013.748388. Epub 2013 Jan 28.
Results Reference
background
PubMed Identifier
31257574
Citation
Centeno Tablante E, Pachon H, Guetterman HM, Finkelstein JL. Fortification of wheat and maize flour with folic acid for population health outcomes. Cochrane Database Syst Rev. 2019 Jul 1;7(7):CD012150. doi: 10.1002/14651858.CD012150.pub2.
Results Reference
background
PubMed Identifier
25898711
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.
Results Reference
background

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Effectiveness of Fortification With Folic Acid and Vitamin B12 Among Teenage Girls

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