Injected B‑vitamin combination versus oral B12 pills

Efficacy and Safety of a Parenterally Administered Fixed Vitamin Combination (Vitamin B6, B12 and Folic Acid) On Vitamin B12 Status and Methylation Capacity in Cobalamin Deficiency Compared to Oral Vitamin B12 Supplementation

This trial will test whether an injected combination of B vitamins works as well and is as safe as taking B12 by mouth for adults with vitamin B12 deficiency.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medice Arzneimittel Pütter GmbH & Co KG (Industry-sponsored)
• Locations: 2 sites (Kharkiv and 1 other locations)
• Trial ID: NCT07029698 on ClinicalTrials.gov

What this trial studies

This phase 4 interventional comparison enrolls adults with vitamin B12 deficiency (serum B12 < 350 pmol/L) who receive either an intramuscular combination of B vitamins (including cyanocobalamin, B6, and folic acid) or oral cyanocobalamin mono therapy. The primary outcome is the change from baseline in serum vitamin B12 concentration after 4 weeks (28 days) of treatment. Secondary outcomes include holotranscobalamin, homocysteine, methylmalonic acid, combined B12 markers (cB12), folic acid, vitamin B6, SAM and SAH levels and the SAM/SAH ratio, along with patient-reported wellbeing and quality-of-life measures (WHO-5, SF-36, EQ-5D VAS). Safety and tolerability of the two treatment approaches are monitored throughout the treatment period.

Who should consider this trial

Good fit: Adults aged 18 and older with laboratory-confirmed vitamin B12 deficiency (serum B12 < 350 pmol/L) who can attend the study visits and, if female of childbearing potential, agree to the required contraception measures.

Not a fit: People without B12 deficiency, those already on effective replacement therapy, pregnant women not meeting contraceptive rules, or individuals with contraindications to intramuscular injections are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the injected B‑vitamin combination could provide a safe alternative to oral B12 that more rapidly or reliably restores B12 and related metabolic markers, particularly for patients with absorption issues.

How similar studies have performed: High-dose oral cyanocobalamin has corrected deficiency in many prior trials, but direct head-to-head data comparing injected multivitamin combinations to oral mono‑B12 therapy are limited.

Eligibility criteria

Inclusion Criteria:

1. Provision of written informed consent to participate in the study (according to Order of the Ministry of Health of Ukraine No. 690 (with amendments)).
2. Female and male patients aged ≥18.
3. Vitamin B12 deficiency, defined as serum vitamin B12 \< 350 pmol/L.
4. Female patients of childbearing potential (WOCBP) must be using two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., with the exception of oral contraceptives), from the time of screening and for the duration of the study, through study completion and for 1 month following study completion. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. All female patients of childbearing potential must have negative pregnancy test results at screening. An additional pregnancy test will be performed on Days 0, 28, 56.
5. Able to communicate well with the investigator and able to understand and comply with the requirements of the study.
6. Patients are otherwise in relatively good health as determined by past medical history, physical examination, vital signs, and laboratory tests at screening (V -1).

Exclusion Criteria:

1. Active or recent vitamin B12, folic acid, B6 intake (the subject must not receive vitamin B12, folic acid, B6 drugs or food supplements for at least 6 months).
2. Participation in a previous clinical study with vitamin B12 within the 6 months prior to screening.
3. Any contraindication to one of the study drugs.
4. Pregnant or nursing (lactating) women.
5. Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation.
6. Subjects with anemia (hemoglobin \< 10 mg/dL) or significant neurological symptoms due to vitamin B12 deficiency.
7. Any diseases that prevent intrinsic-factor independent passive diffusion in the small intestine (e.g. ileum resection)
8. Current drug addiction and/or alcohol abuse as evidenced by patient history and/or as determined by the investigator at V-1.
9. Cognitive or behavioural abnormalities that could impair the capacity to give informed consent or carry out protocol-specified procedures.
10. Inability to take oral medication.
11. Inability or unwillingness to comply with the study protocol.
12. Previous (last 6 months) or current participation in another clinical study.
13. Other medical, neuropsychiatric, or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.
14. Subjects who are in a dependent relationship with the Investigator or the Sponsor.
15. Subjects unwilling to give written informed consent to saving and/or propagation of anonymised medical data

Where this trial is running

Kharkiv and 1 other locations

• State institution "V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine" — Kharkiv, Ukraine (Recruiting)
• Private Enterprise Private Manufacturing Company "Acinus" — Kropyvnytskyi, Ukraine (Recruiting)

Study contacts

• Study coordinator: Igor Zupanets, Prof.Dr.

Conditions Vitamin B12 Deficiency; Vitamin B12 deficiency; Vitamin B12 status; methylation capacity; holotranscobalamin; homocysteine; methylmalonic acid; folic acid