A Study to See if a Combination of Vitamins That is Injected Into a Muscle is as Good and Safe as a Vitamin That is Taken by Mouth (EASYVIT)

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

Primary efficacy objective:

To investigate the effects of a parenterally vitamin B12 combination treatment versus an oral vitamin B12 mono therapy on the vitamin B12 status in female and male patients as determined by the change from baseline in serum vitamin B12 concentration after 4 weeks (28 days) of treatment.

Secondary efficacy objectives:

To evaluate the effects of a parenterally vitamin B12 combination versus an oral vitamin B12 mono therapy after 4 weeks of treatment on:

• Serum holotranscobalamin
• Serum homocysteine
• Serum methylmalonic acid
• Combined vitamin B12 markers (cB12)
• Serum folic acid
• Serum vitamin B6
• Serum S-adenosylmethione (SAM)
• Serum S-adenosylhomocysteine (SAH)
• SAM/SAH ratio
• WHO-5 Well-Being Index
• Medical Outcomes Study Questionnaire Short Form 36 Health Survey (SF-36)
• Visual analogue scale (VAS) EQ-5D.

Safety objectives:

To evaluate the safety and tolerability of oral vitamin B12 mono therapy versus intramuscular vitamin B12 combination.

Study Overview

• Status: Recruiting
• Conditions: Vitamin B12 Deficiency
• Intervention / Treatment: Drug: Vitamin B12, Vitamin B6, Folic acid; Drug: Vitamin B12 (Cyanocobalamin)

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Igor Zupanets, Prof.Dr.; Phone Number: +380679093809; Email: igorzupanets@gmail.com
• Study Contact Backup: Name: Tetyana Kolodyezna, PhD; Phone Number: +380937387790; Email: kolodeznaya@aisconsulting.com.ua

Study Locations

• Ukraine
  • Kharkiv, Ukraine, 61002
    • Recruiting
    • State institution "V. Danilevsky Institute for Endocrine Pathology Problems of the NAMS of Ukraine"
    • Contact: Sergiy Popov, Prof., Dr.; Phone Number: +380985773355; Email: SBP271@gmail.com
    • Principal Investigator: Sergiy Popov, Prof., Dr.
    • Sub-Investigator: Nonna Kravchun, Prof., Dr.
  • Kropyvnytskyi, Ukraine, 25006
    • Recruiting
    • Private Enterprise Private Manufacturing Company "Acinus"
    • Contact: Nataliia Bezugla, PhD; Phone Number: +380661908073; Email: npbezugla@gmail.com
    • Principal Investigator: Igor Zupanets, Prof., Dr.
    • Sub-Investigator: Nataliia Bezugla, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin injection; 1 injection twice weekly at the clinical site. Totally 8 injections through 4 week treatment period	Drug: Vitamin B12, Vitamin B6, Folic acid; A solution for intramuscular injection of fixed vitamin combination (5 mg vitamin B6, 1 mg B12 and 1,05 mg folic acid ); Other Names: Medivitan® iM
Active Comparator: Vitamin B12 tablet; 1 oral tablet once daily in the morning. Totally 28 tablets at approximately the same time each day through 4 week treatment period	Drug: Vitamin B12 (Cyanocobalamin); oral tablets of 1mg Vitamin B12; Other Names: B12 Ankermann®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin B12	Effects of treatment on serum vitamin B12	Change from baseline at day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Holotranscobalamin	Effects of treatment on serum holotranscobalamin	Change from baseline at day 28 and at follow up at day 56
Homocystein	Effects of treatment on serum homocystein	Change from baseline at day 28 and at follow up at day 56
Methylmalonic acid	Effects of treatment on serum methylmalonic acid	Change from baseline at day 28 and at follow up at day 56
Combined vitamin B12 marker (cB12)	Effects of treatment on cB12. Combined vitamin B12 markers (cB12) will be statistically calculated using the levels of Serum holotranscobalamin, Serum homocysteine, Serum methylmalonic acid. cB12 (cB12=log10[(holoTC x B12)/(MMA x Hcy)]-(age factor).	Change from baseline at day 28 and at follow up at day 56
Serum S-adenosylmethione (SAM)	Effects of treatment on serum S-adenosylmethione (SAM)	Change from baseline at day 28 and at follow up at day 56
Serum S-adenosylhomocysteine (SAH)	Effects of treatment on serum S-adenosylhomocysteine (SAH)	Change from baseline at day 28 and at follow up at day 56
SAM/SAH ratio	The change of the ratio will be assessed statistically using the levels of Serum S-adenosylmethione (SAM) and Serum S-adenosylhomocysteine (SAH)	Change from baseline at day 28 and at follow up at day 56
Quality of life assessed with SF-36	Effects of treatment on SF-36 questionnaire (from 0 to 100 points in each of the eight subscales, where the higher score means the higher quality of patient's life in each domain)	Change from baseline at day 28 and at follow up at day 56
Quality of life assessed with WHO-5 questionnaire	Effects of treatment on WHO-5 questionnaire (from 0 to 25, where the higher score means the higher quality of patient's life)	Change from baseline at day 28 and at follow up at day 56
Quality of life assessed with VAS EQ-5D	Effects of treatment on visual analogue scale EQ-5D (from 0 "the worst possible quality of life" to 10 "the best possible quality of life")	From baseline to day 28 and at follow up at day 56

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety objectives	The evaluation of safety will be conducted through a comprehensive analysis of adverse events.	assessed through 56 days of patient's participation

Collaborators and Investigators

• Sponsor: Medice Arzneimittel Pütter GmbH & Co KG

Publications and helpful links

General Publications

• Topp CW, Ostergaard SD, Sondergaard S, Bech P. The WHO-5 Well-Being Index: a systematic review of the literature. Psychother Psychosom. 2015;84(3):167-76. doi: 10.1159/000376585. Epub 2015 Mar 28.
• Naurath HJ, Riezler R, Putter S, Ubbink JB. Does a single vitamin B-supplementation induce functional vitamin B-deficiency? Clin Chem Lab Med. 2001 Aug;39(8):768-71. doi: 10.1515/CCLM.2001.128.
• Ubbink JB, van der Merwe A, Delport R, Allen RH, Stabler SP, Riezler R, Vermaak WJ. The effect of a subnormal vitamin B-6 status on homocysteine metabolism. J Clin Invest. 1996 Jul 1;98(1):177-84. doi: 10.1172/JCI118763.
• Fedosov SN, Brito A, Miller JW, Green R, Allen LH. Combined indicator of vitamin B12 status: modification for missing biomarkers and folate status and recommendations for revised cut-points. Clin Chem Lab Med. 2015 Jul;53(8):1215-25. doi: 10.1515/cclm-2014-0818.
• Metaxas C, Mathis D, Jeger C, Hersberger KE, Arnet I, Walter P. Early biomarker response and patient preferences to oral and intramuscular vitamin B12 substitution in primary care: a randomised parallel-group trial. Swiss Med Wkly. 2017 Apr 7;147:w14421. doi: 10.4414/smw.2017.14421. eCollection 2017.
• Smith AD, Warren MJ, Refsum H. Vitamin B12. Adv Food Nutr Res. 2018;83:215-279. doi: 10.1016/bs.afnr.2017.11.005. Epub 2018 Feb 2.
• Conzade R, Koenig W, Heier M, Schneider A, Grill E, Peters A, Thorand B. Prevalence and Predictors of Subclinical Micronutrient Deficiency in German Older Adults: Results from the Population-Based KORA-Age Study. Nutrients. 2017 Nov 23;9(12):1276. doi: 10.3390/nu9121276.
• 1. Vitamin B12 (Cobalamine). Referenzwerte für die Nährstoffzufuhr. Bonn, Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für Ernährung, Schweizerische Gesellschaft für Ernährung (Hrsg.). 4. Aktualisierte Ausgabe 2018.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: May 1, 2025
• First Submitted That Met QC Criteria: June 18, 2025
• First Posted (Actual): June 19, 2025

Study Record Updates

• Last Update Posted (Actual): June 19, 2025
• Last Update Submitted That Met QC Criteria: June 18, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: methylmalonic acid; homocysteine; vitamin B6; folic acid; S-adenosylhomocysteine; Vitamin B12 deficiency; holotranscobalamin; Vitamin B12 status; methylation capacity; S-adenosylmethione
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin B Deficiency; Vitamin B 12 Deficiency; Physiological Effects of Drugs; Micronutrients; Hematinics; Folic Acid; Vitamin B 12; Hydroxocobalamin; Vitamins; Vitamin B Complex; Pyridoxal; Pyridoxine; Vitamin B 6
• Other Study ID Numbers: 6630-4200-42

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No