Vitamin B 12 DeficiencyNCT03365583
The Impact of Vitamin B12 Deficiency on Infant Gut Microbiota
An observational study of Vitamin B 12 Deficiency, run by Marmara University at 1 site in Turkey (Türkiye).
Trial summary
Vitamin B12 plays important roles in DNA synthesis and neurological functions. Vitamin B12 deficiency is one of the most common micronutrient deficiencies and it has become increasingly more frequent in infants. Read more about this study
- Who is it for?
- Ages 4 to 6 monthsHealthy volunteers can take part
- Conditions the study is for
- Vitamin B 12 Deficiency
- How many people
- 90 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 3 Mar 2017to 3 Nov 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 6 months
- All sexes
- Healthy volunteers accepted
- Child
Study population: Healthy term exclusively breastfed infants aged between 4 to 6 months who fulfill the inclusion criteria are enrolled
Who may be able to join
- must be >37 gestational weeks, birth weight must be >2500 gr, must be exclusively breastfed there should be no congenital anomalies, hemoglobin should be ≥10 g/dL,
Who cannot join
- prematurity, low birth weight, intrapartum antibiotic use, current or previous use of infant formula, malnutrition, use of iron supplements, use of antibiotics, use of probiotics within the last 8 weeks before study entry, and being introduced to solid foods
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Marmara University School of Medicine
Istanbul
About this study
Official title: Comparison of Gut Microbial Composition in Breastfed Infants With and Without Vitamin B12 Deficiency
Vitamin B12 plays important roles in DNA synthesis and neurological functions. Vitamin B12 deficiency is one of the most common micronutrient deficiencies and it has become increasingly more frequent in infants. The deficiency develops more often between 4 to 12 months of age, coinciding with the decreased fetal storage. The highest rates of vitamin B12 deficiency were observed among infants who are breastfed by mothers receiving a diet low in vitamin B12.
The main objective of this study is to compare the gut microbial composition of healthy term exclusively breastfed infants with or without vitamin B12 deficiency. We hypothesized that gut microbiome differs between vitamin B12 deficient and control infants; pathogenic bacteria are hypothesized to be higher, and beneficial bacteria to be lower in vitamin B12 deficient infants as compared to control.
Read more
An observational study in the Marmara University Pendik Research and Training Hospital well child outpatient clinic is conducted in 90 infants. Participants aged between 4 to 6 months who fulfill the inclusion criteria are enrolled.
Inclusion criteria are term birth (>37 gestational weeks), birth weight >2500 gr, absence of congenital anomalies, hemoglobin ≥10 g/dL, and exclusive breastfeeding.
Exclusion criteria include prematurity, low birth weight, intrapartum antibiotic use, current or previous use of infant formula, malnutrition, use of iron supplements, infant use of antibiotics, use of probiotics within the last 8 weeks before study entry, and introduction to solid foods.
Primary outcome measures:Microbial counts, and a comparison of type and abundance of species (predominant, pathogenic, and opportunistic bacteria, yeast, and parasites) between vitamin B12 deficient and sufficient subjects will be assessed.
Secondary outcome measures: Fecal bacterial communities will be assessed before and after treatment in a subgroup of infants.
Each stool sample is collected from cloth diapers, and placed in sterile collection tubes. Samples are kept at 4 C and in less than 5 hours, they are frozen at -80 C until further analysis. Specimens are transported on dry ice to the Diagen Inc for DNA extraction.
For the extraction protocol, QuickGene (Kurabo, North America) extraction device will be used.
The extracted DNA samples will be sent to Diversigen Inc (Houston, USA) for analysis. Fecal microbiota composition will be analyzed with 16S ribosomal ribonucleic acid (rRNA) sequencing.
Read the detailed description
Vitamin B12 plays important roles in DNA synthesis and neurological functions. Vitamin B12 deficiency is one of the most common micronutrient deficiencies and it has become increasingly more frequent in infants. The deficiency develops more often between 4 to 12 months of age, coinciding with the decreased fetal storage. The highest rates of vitamin B12 deficiency were observed among infants who are breastfed by mothers receiving a diet low in vitamin B12. The data on prevalence of vitamin B12 deficiency in Turkey mainly relate to pregnant women and varies between 34% to 72%. In our previous study, 36.3% of the infants (n=222) were vitamin B12 deficient. The prevalence was even higher (43%) in infants exclusively breastfed for 6 months.
The physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively. Although it is known that individuals with high bacterial loads in their small intestines tend to have low cobalamin status, less is known about its effects on the developing gut microbiota. It is suggested that early environmental factors influencing gut microbiota during this crucial developmental period can lead to long term consequences on health and disease. The data available is mostly limited to the effects of iron. The review of the literature has not yielded any study, which investigates the effects of vitamin B12 on the developing gut microbiota.
The study is conducted at Marmara University well child outpatient clinic. The clinic is hospital based and located in Pendik, Istanbul. The outpatient clinic provides well child care; and besides anthropometric measurements, infants are routinely screened for anemia at 4 to 6 months of age.
Ninety-two exclusively breastfed infants are approached for eligibility. Two infants are excluded due to prior antibiotic use and 90 infants are enrolled.
Fecal collection tubes are given to the parents of infants who fulfill the inclusion criteria during routine blood withdrawal. For the reporting, serum vitamin B12 <203 pg/mL is considered as vitamin B12 deficiency, and ≥203 pg/mL as vitamin B12 sufficient.
Infants with vitamin B12 deficiency are treated with intramuscular vitamin b12 (hydroxycobalamin), 250-500 mcg twice weekly for a week, and then 500 mcg weekly for another 3 weeks. One month after the supplementation in the recommended dose, stools are recollected in a subgroup of subjects (n=11) with vitamin B12 deficiency.
Samples are kept at 4 C and in less than 5 hours, they are frozen at -80 C until further analysis.
Questionnaires are completed, antropometric measures are taken and fecal samples are transported on dry ice to the Diagen Inc for DNA extraction DNA extraction will be performed by Diagen Inc. For the extraction protocol, QuickGene (Kurabo, North America) extraction device will be used.
The extracted DNA samples will be sent to Diversigen Inc (Houston, USA) for 16S rRNA Gene V4 region sequencing.
- Conditions
- Vitamin B 12 Deficiency
- Keywords
- Vitamin B12, Microbiome, infant
- Medical subject headings
- Vitamin B 12 Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin B12 deficiency | No intervention will be administered for this study. Serum vitamin B12 <203 pg/mL is considered as vitamin B12 deficiency. Fecal microbiota composition will be analyzed with 16S rRNA sequencing. In a subgroup of infants (n=11), fecal samples will be recollected after the treatment as usual | |
| Vitamin B12 sufficient | Serum vitamin B12 ≥203 pg/mL is considered as vitamin B12 sufficient Fecal microbiota composition will be analyzed with 16S rRNA sequencing. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gut microbial community differences between infants with vitamin B12 deficiency and infants with sufficient vitamin B12
Microbial counts, and a comparison of type and abundance of species (predominant, pathogenic, and opportunistic bacteria, yeast, and parasites) between vitamin B12 deficient and sufficient subjects will be assessed
Measured: DNA extraction and fecal microbiota composition with 16S rRNA sequencing is anticipated to be completed at June 2018
Secondary outcomes (1)
Gut microbial community differences within subject
Fecal bacterial communities will be assessed before and after treatment as usual in a subgroup of vitamin B12 deficient infants
Measured: Recollection of stool samples one month after treatment as usual. DNA extraction and fecal microbiota composition with 16S rRNA sequencing is anticipated to be completed at June 2018
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2017
- Study start3 Mar 2017
- Primary completion3 Sep 2017
- Study completion3 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vitamin B 12 DeficiencyStudies of the same condition, open and under way.
- More trials run by Marmara UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marmara University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Perran Boran, MD, PhD, Principal investigator, Marmara University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03365583
- Sponsor's protocol ID
- 09.2016.137
- Status last verified
- Mar 2019
- First submitted
- 2 Dec 2017
- Last updated
- 6 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Gut Microbial Composition in Breastfed Infants With and Without Vitamin B12 Deficiency
- ClinicalTrials.gov ID
- NCT03365583
- Acronym / sponsor ID
- 09.2016.137
- Conditions
- Vitamin B 12 Deficiency
- Keywords
- Vitamin B12, Microbiome, infant
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Marmara UniversityUniversity, hospital or other
- Study start
- 3 Mar 2017 (actual)
- Primary completion
- 3 Sep 2017 (actual)
- Study completion
- 3 Nov 2017 (actual)
- First posted
- 7 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Vitamin B12 plays important roles in DNA synthesis and neurological functions. Vitamin B12 deficiency is one of the most common micronutrient deficiencies and it has become increasingly more frequent in infants. The deficiency develops more often between 4 to 12 months of age, coinciding with the decreased fetal storage. The highest rates of vitamin B12 deficiency were observed among infants who are breastfed by mothers receiving a diet low in vitamin B12.
The main objective of this study is to compare the gut microbial composition of healthy term exclusively breastfed infants with or without vitamin B12 deficiency. We hypothesized that gut microbiome differs between vitamin B12 deficient and control infants; pathogenic bacteria are hypothesized to be higher, and beneficial bacteria to be lower in vitamin B12 deficient infants as compared to control.
An observational study in the Marmara University Pendik Research and Training Hospital well child outpatient clinic is conducted in 90 infants. Participants aged between 4 to 6 months who fulfill the inclusion criteria are enrolled.
Inclusion criteria are term birth (>37 gestational weeks), birth weight >2500 gr, absence of congenital anomalies, hemoglobin ≥10 g/dL, and exclusive breastfeeding.
Exclusion criteria include prematurity, low birth weight, intrapartum antibiotic use, current or previous use of infant formula, malnutrition, use of iron supplements, infant use of antibiotics, use of probiotics within the last 8 weeks before study entry, and introduction to solid foods.
Primary outcome measures:Microbial counts, and a comparison of type and abundance of species (predominant, pathogenic, and opportunistic bacteria, yeast, and parasites) between vitamin B12 deficient and sufficient subjects will be assessed.
Secondary outcome measures: Fecal bacterial communities will be assessed before and after treatment in a subgroup of infants.
Each stool sample is collected from cloth diapers, and placed in sterile collection tubes. Samples are kept at 4 C and in less than 5 hours, they are frozen at -80 C until further analysis. Specimens are transported on dry ice to the Diagen Inc for DNA extraction.
For the extraction protocol, QuickGene (Kurabo, North America) extraction device will be used.
The extracted DNA samples will be sent to Diversigen Inc (Houston, USA) for analysis. Fecal microbiota composition will be analyzed with 16S ribosomal ribonucleic acid (rRNA) sequencing.
Detailed description
Vitamin B12 plays important roles in DNA synthesis and neurological functions. Vitamin B12 deficiency is one of the most common micronutrient deficiencies and it has become increasingly more frequent in infants. The deficiency develops more often between 4 to 12 months of age, coinciding with the decreased fetal storage. The highest rates of vitamin B12 deficiency were observed among infants who are breastfed by mothers receiving a diet low in vitamin B12. The data on prevalence of vitamin B12 deficiency in Turkey mainly relate to pregnant women and varies between 34% to 72%. In our previous study, 36.3% of the infants (n=222) were vitamin B12 deficient. The prevalence was even higher (43%) in infants exclusively breastfed for 6 months.
The physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively. Although it is known that individuals with high bacterial loads in their small intestines tend to have low cobalamin status, less is known about its effects on the developing gut microbiota. It is suggested that early environmental factors influencing gut microbiota during this crucial developmental period can lead to long term consequences on health and disease. The data available is mostly limited to the effects of iron. The review of the literature has not yielded any study, which investigates the effects of vitamin B12 on the developing gut microbiota.
The study is conducted at Marmara University well child outpatient clinic. The clinic is hospital based and located in Pendik, Istanbul. The outpatient clinic provides well child care; and besides anthropometric measurements, infants are routinely screened for anemia at 4 to 6 months of age.
Ninety-two exclusively breastfed infants are approached for eligibility. Two infants are excluded due to prior antibiotic use and 90 infants are enrolled.
Fecal collection tubes are given to the parents of infants who fulfill the inclusion criteria during routine blood withdrawal. For the reporting, serum vitamin B12 <203 pg/mL is considered as vitamin B12 deficiency, and ≥203 pg/mL as vitamin B12 sufficient.
Infants with vitamin B12 deficiency are treated with intramuscular vitamin b12 (hydroxycobalamin), 250-500 mcg twice weekly for a week, and then 500 mcg weekly for another 3 weeks. One month after the supplementation in the recommended dose, stools are recollected in a subgroup of subjects (n=11) with vitamin B12 deficiency.
Samples are kept at 4 C and in less than 5 hours, they are frozen at -80 C until further analysis.
Questionnaires are completed, antropometric measures are taken and fecal samples are transported on dry ice to the Diagen Inc for DNA extraction DNA extraction will be performed by Diagen Inc. For the extraction protocol, QuickGene (Kurabo, North America) extraction device will be used.
The extracted DNA samples will be sent to Diversigen Inc (Houston, USA) for 16S rRNA Gene V4 region sequencing.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vitamin B12 deficiency | – | –No intervention will be administered for this study. Serum vitamin B12 <203 pg/mL is considered as vitamin B12 deficiency. Fecal microbiota composition will be analyzed with 16S rRNA sequencing. In a subgroup of infants (n=11), fecal samples will be recollected after the treatment as usual |
| Vitamin B12 sufficient | – | –Serum vitamin B12 ≥203 pg/mL is considered as vitamin B12 sufficient Fecal microbiota composition will be analyzed with 16S rRNA sequencing. |
Who may qualify
- Ages
- 4 to 6 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Healthy term exclusively breastfed infants aged between 4 to 6 months who fulfill the inclusion criteria are enrolled
Key inclusion criteria (1 listed)
- must be >37 gestational weeks, birth weight must be >2500 gr, must be exclusively breastfed there should be no congenital anomalies, hemoglobin should be ≥10 g/dL,
Key exclusion criteria (1 listed)
- prematurity, low birth weight, intrapartum antibiotic use, current or previous use of infant formula, malnutrition, use of iron supplements, use of antibiotics, use of probiotics within the last 8 weeks before study entry, and being introduced to solid foods
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Gut microbial community differences between infants with vitamin B12 deficiency and infants with sufficient vitamin B12
Time frame: DNA extraction and fecal microbiota composition with 16S rRNA sequencing is anticipated to be completed at June 2018
Microbial counts, and a comparison of type and abundance of species (predominant, pathogenic, and opportunistic bacteria, yeast, and parasites) between vitamin B12 deficient and sufficient subjects will be assessed
1 secondary outcome
Gut microbial community differences within subject
Time frame: Recollection of stool samples one month after treatment as usual. DNA extraction and fecal microbiota composition with 16S rRNA sequencing is anticipated to be completed at June 2018
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Perran Boran, MD, PhD principal investigator
Marmara University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Vitamin B 12 Deficiency, run by Marmara University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Gut microbial community differences between infants with vitamin B12 deficiency and infants with sufficient vitamin B12 (time frame: DNA extraction and fecal microbiota composition with 16S rRNA sequencing is anticipated to be completed at June 2018). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2019.