(P27-057-25) Single-Blinded, Stratified, Dose Ranging Trial to Assess Pharmacokinetics and Identify Optimal Dose of Vitamin B12 in Pregnancy in Tanzania

Objectives: Clinical studies of B12 supplementation during pregnancy with heterogeneous designs have demonstrated limited or non-significant changes on vitamin B12 status indicators compared to placebo.

We sought to determine the optimal dose of B12 supplementation to improve B12 status during pregnancy in an inpatient, controlled feeding trial.

Methods: We conducted a phase 1, single-blinded, stratified, multiple ascending dose clinical trial from June 2023 to March 2024 at the Bagamoyo Clinical Trial Unit of Ifakara Health Institute (IHI), in which pregnant and non-pregnant participants were sequentially assigned to each of the three ascending doses of 2.6 ug, 10 ug, and 50 ug as a single dose, or 25 ug given twice daily. Participants were stratified by baseline serum B12 status into “Sufficient” ( > 220 pmol/L) and “Insufficient” ( < 220 pmol/L). The trial participants resided in the clinical trial facility for 4 weeks to ensure controlled feeding and direct observation of B12 supplementation by trained research staff (NCT05426395).

Results: We screened 112 participants and enrolled 40 pregnant and 10 non-pregnant participants; all participants completed the study. Baseline demographic characteristics were similar across all study groups. The mean B12 serum concentration on day 29 (unadjusted for baseline and sufficiency status) was 313.1, 232.4, 400.9 and 499.6 pmol/L for the 2.6 ug, 10 ug, 50 ug, and 50 ug (25 ug given twice daily) groups respectively. The mean change from baseline in serum total vitamin B12 concentration was higher in 50 ug (25 ug given twice daily) (247.09 pmol/L) compared to 2.6 ug (18.01 pmol/L), and 10 ug (11.67 pmol/L) (adjusted p value < 0.001). Steady state was achieved for serum total vitamin B12 levels by day 10 across all groups.

Conclusions: Our results indicate that high dose (50 ug) B12 supplementation, particularly when split into two 25 ug doses, results in the most significant B12 status improvement in pregnancy. This dose may be considered in large, well designed trials assessing the effect of B12 supplementation on maternal and newborn health outcomes.

Funding Sources: Bill and Melinda Gates Foundation