Vitamin B 12 DeficiencyPhase 1MM4MN-B12NCT05426395

Vitamin B12 Dose Escalation Trial in Pregnancy

A Phase 1 study testing Vitamin B12 2.6 µg, Vitamin B12 10 µg and Vitamin B12 50 µg in people with Vitamin B 12 Deficiency, run by George Washington University at 1 site in Tanzania.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Vitamin B12 is a cofactor for 2 enzymes that have essential functions in pregnancy, both for maternal health and for fetal development. However, there is currently limited data regarding the metabolic fate and optimal dose of supplemental vitamin B12 and its relationship to vitamin B12 status in pregnancy. Read more about this study

Who is it for?: Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for: Vitamin B 12 Deficiency
What is being tested?: Vitamin B12 2.6 µg, Vitamin B12 10 µg and Vitamin B12 50 µg
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteTanzania
Study dates: 5 Jun 2023to Dec 2026
Phase: Phase 1
Are there results?: Not yet: the study is under way

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 18 to 45 years
Women only
Healthy volunteers accepted
Adult

The inclusion criteria for pregnant women are as follows:

Pregnant female
Has an estimated gestational age of 25 to 28 weeks at study initiation
Is between the ages of 18 and 45 years of age
Lives in the study area and does not plan to travel outside of the study area for the duration of the trial
Consents to participate in the trial

The exclusion criteria for pregnant women are as follows:

Known multiple pregnancy (e.g. twins, triplets)
Has severe anemia (hemoglobin <7 g/dL)
Has pre-pregnancy or early pregnancy Body Mass Index ≥ 35 kg/m2
Has a self-reported pre-pregnancy history of type II diabetes mellitus, hypertension, or hypercholesterolemia.
Has currently diagnosed preeclampsia or eclampsia.
Has currently diagnosed gestational diabetes.
Has currently diagnosed renal, liver, autoimmune, or bleeding disorders. The investigators will also assess all women for clinical signs of liver disease including: jaundice or yellowing of skin/sclera/mucosa, right upper quadrant tenderness or pain. All women will be given a liver function test, regardless of clinical signs of liver disease. The tests include: serum Alanine aminotransferase (ALT) and serum Aspartate aminotransferase (AST). Abnormal liver function is defined as the following in this study for women who the investigators screened during the 2nd trimester (25-26 weeks), ALT below 2 or above 33 U/L, or AST below 3 or above 33 U/L; for women screened during the 3rd trimester (27-28 weeks), ALT below 2 or above 25 U/L, or AST below 4 or above 32 U/L (25). Those with liver disease or abnormal liver function will be excluded from the study and referred for treatment.
Has currently diagnosed congestive heart failure. The investigators will first look for clinical signs of heart failure, and the investigators will focus on the following: i) Fatigue with limitation in performance of normal activities; ii) Coughing, wheezing and breathing difficulty because of lung congestion; iii) Swelling of ankles, feet and legs; and iv) Shortness of breath especially when lying flat. The investigators will only perform lab testing for those who have clinical manifestation, and refer them to appropriate and timely care.
Has a history of significant gastrointestinal surgeries, such as bariatric surgery, cholecystectomy, or other surgical procedures affecting the stomach, liver, bile ducts and/or small intestine that may disrupt enterohepatic recycling of vitamin B12.
Has a condition requiring the use of the following medications: H2 blockers, proton pump inhibitors, or prokinetic agents.
Reports regular use of an over-the-counter, high dose vitamin B12 supplementation. (This criteria does not refer to normal prenatal vitamin supplements which typically include approximately 1 RDA of vitamin B12 or 2.6 ug of vitamin B12. Women using multiple micronutrient supplements, or MMS, are eligible for the study).
Reports cigarette smoking or tobacco chewing
Reports heavy alcohol use (>3 drinks per day, or >7 drinks per week)
Current malaria infection (per rapid diagnostic)
HIV/AIDS infection (due to potential interaction between first-line antiretroviral dolutegravir and multivitamins that has been shown to decrease dolutegravir exposure by about 33%).
Has a known allergy to corn or hydroxyethyl starch (HES).

The inclusion criteria for non-pregnant women are as follows:

Is between the ages of 18 and 45 years of age.
Lives in the study area and does not plan to travel outside of the study area for the duration of the trial
Consents to participate in the trial

The exclusion criteria for non-pregnant women are as follows:

Has severe anemia (hemoglobin <8 g/dL)
Has Body Mass Index ≥ 35 kg/m2
Has a self-reported diagnosis of type II diabetes mellitus, hypertension, or hypercholesterolemia.
Has currently diagnosed renal, liver, autoimmune, or bleeding disorders. The investigators will also assess all women for clinical signs of liver disease including: jaundice or yellowing of skin/sclera/mucosa, right upper quadrant tenderness or pain. Any woman with clinical signs of liver disease will be given a liver function test including: ALT, AST (26,27). Those with liver disease will be excluded from the study and referred for treatment.
Has currently diagnosed congestive heart failure.
Has a history of significant gastrointestinal surgeries, such as bariatric surgery, cholecystectomy, or other surgical procedures affecting the stomach, liver, bile ducts and/or small intestine that may disrupt enterohepatic recycling of vitamin B12.
Has a condition requiring the use of the following medications: H2 blockers, proton pump inhibitors, or prokinetic agents.
Reports regular use of an over-the-counter, high dose vitamin B12 supplementation.
Reports cigarette smoking or tobacco chewing
Reports heavy alcohol use (>3 drinks per day, or >7 drinks per week)
Current malaria infection (per rapid diagnostic)
HIV/AIDS infection (due to potential interaction between first-line antiretroviral dolutegravir and multivitamins that has been shown to decrease dolutegravir exposure by about 33%).
Has a known allergy to corn or hydroxyethyl starch (HES).

Trial locations and contacts

1 site in 1 country.

Tanzania1 site

Ifakara Health Institute Bagamoyo Clinical Trial Unit (BCTU)
Bagamoyo

Other trials in Tanzania

About this study

Official title: Single-blinded, Stratified, Multiple Ascending Dose Trial to Assess Pharmacokinetics and Identify Optimal Dose of Vitamin B12 in Pregnancy in Tanzania

This is a single-blinded, stratified, dose-ranging trial of maternal vitamin B12 supplementation during pregnancy that will be conducted at the Ifakara Health Institute Bagamoyo Clinical Trial Unit in Tanzania. The investigators will enroll 40 pregnant women (gestational age 25-28 weeks) and 10 non-pregnant women (comparison group). Participants will be blinded to dosing (2.6, 10, and 50 µg) and supplementation will be given for four weeks.

With this trial, the investigators aim to enhance our understanding of vitamin B12 bioavailability during pregnancy in people with sufficient and insufficient baseline B12 status, identify priority dose regimens of vitamin B12 in pregnancy for investigation in later phase clinical trials to be conducted in populations where vitamin B12 insufficiency or deficiency is common, and identify biomarkers of vitamin B12 intake appropriate for pregnancy.

Conditions: Vitamin B 12 Deficiency
Being tested: Vitamin B12 2.6 µg, Vitamin B12 10 µg, Vitamin B12 50 µg
Keywords: Vitamin B12, Pregnancy
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.

Vitamin B12 2.6 µgDrug
There are four groups of women (n = 20 total) who will receive B12 dosing once daily, including group 1a (sufficient baseline B12, pregnant), group 1b (sufficient baseline B12, non-pregnant), group 1c (insufficient baseline B12, pregnant), and group 1d (insufficient baseline B12, non-pregnant).
Vitamin B12 10 µgDrug
There are two groups of women (n = 10 total) who will receive B12 dosing once daily, including group 2a (sufficient baseline B12, pregnant) and group 2b (insufficient baseline B12, pregnant).
Vitamin B12 50 µgDrug
The participants (n = 20 total) will be randomly assigned to receive either a once per day B12 dose or a twice per day B12 dose. The four groups at this dose level include: group 3a (sufficient baseline B12, pregnant, Q12), group 3b (sufficient baseline B12, Q24), group 3c (insufficient baseline B12, pregnant, Q12), group 3d (insufficient baseline B12, Q24).

Study groups in NCT05426395
Study group	Role	What they receive
Dose 1 (2.6 µg)	Active comparator	Adding Vitamin B12 at a dose of 2.6 µg Receives: Drug: Vitamin B12 2.6 µg
Dose 2 (10 µg)	Active comparator	Adding Vitamin B12 at a dose of 10 µg Receives: Drug: Vitamin B12 10 µg
Dose 3 (50 µg)	Active comparator	Adding Vitamin B12 at a dose of 50 µg Receives: Drug: Vitamin B12 50 µg

What is being measured

The primary outcome is the main question the study is designed to answer.

Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
The sparse serum vitamin B12 levels measured over 4 weeks at multiple occasions will be used to evaluate the accumulation ratio (steady state B12 level/baseline B12 level) and relative bioavailability between the three doses of B12. The steady state B12 levels will be evaluated descriptively between the three different doses (2.6ug, 10ug and 50ug), different baseline B12 status (sufficient and insufficient), pregnancy status (pregnant and non-pregnant) and other subject specific prognostic factors.
Measured: Over 4 weeks
Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
The sampling of holotranscobalamin II measured over 4 weeks at multiple occasions will be used to evaluate the absorption and disposition of B12. The mean change from baseline steady state B12 levels in pregnant women will be calculated for the three dose cohorts and the magnitude of difference (fold-change) in mean change from baseline steady state B12 levels between doses will be descriptively compared. Additionally, proportion of subjects who achieved or maintained sufficient B12 status will be assessed for each of the three dose cohorts. A dose with a higher fold difference (from 2.6ug) and higher proportion of women on sufficient status will be identified as a priority B12 dose regimen. The investigators will use metabolomics, proteomics, and genomics to identify novel biomarkers that can more robustly and sensitively reflect vitamin B12 status than conventional markers.
Measured: Over 4 weeks
Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
The sampling of the ratio of serum B12 to holotranscobalamin measured over 4 weeks at multiple occasions will be used to evaluate the absorption and disposition of B12. The mean change from baseline steady state B12 levels in pregnant women will be calculated for the three dose cohorts and the magnitude of difference (fold-change) in mean change from baseline steady state B12 levels between doses will be descriptively compared. Additionally, proportion of subjects who achieved or maintained sufficient B12 status will be assessed for each of the three dose cohorts. A dose with a higher fold difference (from 2.6ug) and higher proportion of women on sufficient status will be identified as a priority B12 dose regimen. The investigators will use metabolomics, proteomics, and genomics to identify novel biomarkers that can more robustly and sensitively reflect vitamin B12 status than conventional markers.
Measured: Over 4 weeks

Secondary outcomes (7)

Assessing serum methylmalonic acid (MMA)
Measured: On Day 29
Assessing serum and urinary homocysteine
Measured: On Day 29
Assessing hematological response: hemoglobin
Measured: On Day 29
Assessing hematological response: hematocrit
Measured: On Day 29
Assessing hematological response: erythrocyte count
Measured: On Day 29
Assessing hematological response: mean cell volume
Measured: On Day 29
Assessing hematological response: reticulocyte number
Measured: On Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jun 2023Dec 2026

First posted22 Jun 2022
Study start5 Jun 2023
Primary completion15 Jan 2024
Study completionDec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Vitamin B 12 DeficiencyStudies of the same condition, open and under way.
More trials run by George Washington 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: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized Clinical Trial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05426395
Sponsor's protocol ID: MM4MN-B12 2022
Acronym: MM4MN-B12
Status last verified: Feb 2026
First submitted: 14 Jun 2022
Last updated: 5 Feb 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Lweno O, Reynolds VS, Barberio MD, Klatt KC, Mugusi S, Gopalakrishnan M, Lukmanji Z, Al-Beity FMA, Ahmadzia HK, Arcot A, Gallagher K, Martin LA, Rahnavard A, Gernand AD, Langevin B, Masanja H, Smith ER. Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania. Gates Open Res. 2025 Sep 17;8:95. doi: 10.12688/gatesopenres.15991.2. eCollection 2024.
PubMed 41488590

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Vitamin B12 Supplementation During Pregnancy on Cognitive Development
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All Vitamin B 12 Deficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Single-blinded, Stratified, Multiple Ascending Dose Trial to Assess Pharmacokinetics and Identify Optimal Dose of Vitamin B12 in Pregnancy in Tanzania
ClinicalTrials.gov ID: NCT05426395
Acronym / sponsor ID: MM4MN-B12 / MM4MN-B12 2022
Conditions: Vitamin B 12 Deficiency
Keywords: Vitamin B12, Pregnancy
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 50 participants (actual)
Lead sponsor: George Washington UniversityUniversity, hospital or other
Collaborators: Ifakara Health Institute
Study start: 5 Jun 2023 (actual)
Primary completion: 15 Jan 2024 (actual)
Study completion: Dec 2026 (estimated)
First posted: 22 Jun 2022 (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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3
Model description: Randomized Clinical Trial

Arm	Type	Receives
Dose 1 (2.6 µg)	Active comparator	Drug: Vitamin B12 2.6 µgAdding Vitamin B12 at a dose of 2.6 µg
Dose 2 (10 µg)	Active comparator	Drug: Vitamin B12 10 µgAdding Vitamin B12 at a dose of 10 µg
Dose 3 (50 µg)	Active comparator	Drug: Vitamin B12 50 µgAdding Vitamin B12 at a dose of 50 µg

Who may qualify

Ages: 18 to 45 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Vitamin B12 2.6 µgThere are four groups of women (n = 20 total) who will receive B12 dosing once daily, including group 1a (sufficient baseline B12, pregnant), group 1b (sufficient baseline B12, non-pregnant), group 1c (insufficient baseline B12, pregnant), and group 1d (insufficient baseline B12, non-pregnant).	Drug	Dose 1 (2.6 µg)
Vitamin B12 10 µgThere are two groups of women (n = 10 total) who will receive B12 dosing once daily, including group 2a (sufficient baseline B12, pregnant) and group 2b (insufficient baseline B12, pregnant).	Drug	Dose 2 (10 µg)
Vitamin B12 50 µgThe participants (n = 20 total) will be randomly assigned to receive either a once per day B12 dose or a twice per day B12 dose. The four groups at this dose level include: group 3a (sufficient baseline B12, pregnant, Q12), group 3b (sufficient baseline B12, Q24), group 3c (insufficient baseline B12, pregnant, Q12), group 3d (insufficient baseline B12, Q24).	Drug	Dose 3 (50 µg)

Primary outcome

Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
Time frame: Over 4 weeks
The sparse serum vitamin B12 levels measured over 4 weeks at multiple occasions will be used to evaluate the accumulation ratio (steady state B12 level/baseline B12 level) and relative bioavailability between the three doses of B12. The steady state B12 levels will be evaluated descriptively between the three different doses (2.6ug, 10ug and 50ug), different baseline B12 status (sufficient and insufficient), pregnancy status (pregnant and non-pregnant) and other subject specific prognostic factors.
Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
Time frame: Over 4 weeks
The sampling of holotranscobalamin II measured over 4 weeks at multiple occasions will be used to evaluate the absorption and disposition of B12. The mean change from baseline steady state B12 levels in pregnant women will be calculated for the three dose cohorts and the magnitude of difference (fold-change) in mean change from baseline steady state B12 levels between doses will be descriptively compared. Additionally, proportion of subjects who achieved or maintained sufficient B12 status will be assessed for each of the three dose cohorts. A dose with a higher fold difference (from 2.6ug) and higher proportion of women on sufficient status will be identified as a priority B12 dose regimen. The investigators will use metabolomics, proteomics, and genomics to identify novel biomarkers that can more robustly and sensitively reflect vitamin B12 status than conventional markers.
Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women.
Time frame: Over 4 weeks
The sampling of the ratio of serum B12 to holotranscobalamin measured over 4 weeks at multiple occasions will be used to evaluate the absorption and disposition of B12. The mean change from baseline steady state B12 levels in pregnant women will be calculated for the three dose cohorts and the magnitude of difference (fold-change) in mean change from baseline steady state B12 levels between doses will be descriptively compared. Additionally, proportion of subjects who achieved or maintained sufficient B12 status will be assessed for each of the three dose cohorts. A dose with a higher fold difference (from 2.6ug) and higher proportion of women on sufficient status will be identified as a priority B12 dose regimen. The investigators will use metabolomics, proteomics, and genomics to identify novel biomarkers that can more robustly and sensitively reflect vitamin B12 status than conventional markers.

7 secondary outcomes

Assessing serum methylmalonic acid (MMA)
Time frame: On Day 29
Assessing serum and urinary homocysteine
Time frame: On Day 29
Assessing hematological response: hemoglobin
Time frame: On Day 29
Assessing hematological response: hematocrit
Time frame: On Day 29
Assessing hematological response: erythrocyte count
Time frame: On Day 29
Assessing hematological response: mean cell volume
Time frame: On Day 29
Assessing hematological response: reticulocyte number
Time frame: On Day 29

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
Derived from this study: PubMed 41488590Lweno O, Reynolds VS, Barberio MD, Klatt KC, Mugusi S, Gopalakrishnan M, Lukmanji Z, Al-Beity FMA, Ahmadzia HK, Arcot A, Gallagher K, Martin LA, Rahnavard A, Gernand AD, Langevin B, Masanja H, Smith ER. Single-blinded, stratified, dose ranging trial to assess pharmacokinetics and identify optimal dose of vitamin B12 in pregnancy in Tanzania. Gates Open Res. 2025 Sep 17;8:95. doi: 10.12688/gatesopenres.15991.2. eCollection 2024.
Individual participant dataSharing planned: Undecided

Related trials for Vitamin B 12 Deficiency

RecruitingObservational study
Clinical and Laboratory Study of Methylmalonic Acidemia
Organic Acidemia, Methylmalonic Acidemia
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Active, not recruitingPhase 2/3
Vitamin B12 Supplementation During Pregnancy on Cognitive Development
Pregnancy Related, Vitamin B 12 Deficiency
Not yet recruitingPhase 3
A Study to Evaluate the Effects and Safety of Hydroxocobalamin in Participants With Combined Methylmalonic Academia (cblC Type)
Methylmalonic Acidemia (MMA)

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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vitamin B12 2.6 µg, Vitamin B12 10 µg and Vitamin B12 50 µg in people with Vitamin B 12 Deficiency, run by George Washington University at 1 site in Tanzania.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: under way, not looking for participants, as of the sponsor's last update on 5 Feb 2026. 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 Tanzania. 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.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Assessing the steady state pharmacokinetics of B12 upon oral administration in pregnant women. (time frame: Over 4 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05426395, which also lists 1 linked publication.

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 5 Feb 2026.