Dose-dependent Kinetics of Thiamin in Healthy Volunteers With and Without Functional OCT1 Hepatic Transporters

NCT06122701 · tracked via the Priya Life Science Germany tracker

Sponsor

University Medicine Greifswald

Phase

Not applicable

Started

2023-11-03

Last updated

2025-01-24

Condition(s) studied

Healthy

Investigational drug(s) / intervention(s)

Thiamin p.o.Thiamin i.v.

Thiamin p.o.: A single oral dose of thiamin will be administered in four intervention arms (arm 1: 200 mg, arm 2: 50 mg, arm 3: 10 mg, arm 4: 5 mg) as a drinking solution with 240 ml of still water after an overnight fast. A total of 15 blood samples will be taken at defined time points (baseline; 0.25; 0.5; 0.75; 1.0; 1.5; 2.0; 2.5; 3.0; 3.5; 4.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for plasma and 2.7 ml for whole blood) to determine thiamin, TMP and TDP, and biomarkers of OCT1 transport activity. Urine will be collected during the first 10 hours after thiamin administration.

Thiamin i.v.: A single i.v. dose of thiamin 5 mg with 240 ml of still water after an overnight fast. A total of 15 blood samples will be taken at defined time points (baseline; 0.25; 0.5; 0.75; 1.0; 1.5; 2.0; 2.5; 3.0; 3.5; 4.0; 6.0; 8.0; 10.0; 24.0 h). At each time point, blood will be collected (4.9 ml for plasma and 2.7 ml for whole blood) to determine thiamin, TMP and TDP, and biomarkers of OCT1 transport activity. Urine will be collected during the first 10 hours after thiamin administration.

Study summary

This study investigates the differences in thiamin (vitamin B1) kinetic parameters in two cohorts of healthy volunteers:

Cohort 1) OCT1 wild type genotypes n = 12 Cohort 2) OCT1 deficient genotypes n = 12 Participants will be selected according to their OCT1 genotypes and to achieve best matching according to sex, age, BMI, alcohol consumption, and smoking between Cohort 1 and 2, respectively.

The purpose of this study is:

1. To determine the influence of OCT1 genetic variants on dose-dependent thiamin kinetics after oral administration.
2. To elucidate whether OCT1 genetic variants impact the kinetic properties of orally vs. intravenously administered thiamin.

Eligibility

Sex

ALL

Min age

18 Years

Max age

50 Years

Healthy volunteers

Accepted

Inclusion Criteria: 1. any sex 2. age between 18 and 50 years 3. OCT1 wild type: homozygous for OCT1\*1 OCT "poor transporter": homozygous or heterozygous for OCT1\*3, \*4, \*5, \*6 4. understands the study purpose and design 5. contractually capable and provides signed informed consent form 6. healthy condition or mild and/or well-treated forms of allergies, asthma, hypertension, and orthopedic diseases 7. a maximum of 3 chronically taken drugs not interfering with OCT1 activity Exclusion Criteria: 1. BMI \> 32 kg/m2 and \< 17 kg/m2 2. body weight \< 48 kg 3. known pregnancy or lactation period 4. women: positive urine pregnancy test at screening or kinetic visit 1 of each arm 5. men: hemoglobin \< 13 g/dl (8,07 mmol/l) women: hemoglobin \< 12 g/dl (7,45 mmol/l) 6. elevated liver function tests (1 or more of ALAT, ASAT, yGT, Bilirubin \> 2x ULN) 7. reduced renal function (eGFRMDRD \< 60 ml/min/1,7 m2) 8. QTcF \> 450 ms in screening ECG 9. psychiatric disease requiring recent or actual treatment 10. drug dependency at the time of visit 11. use of recreational drugs more than twice a week 12. any known hypersensitivity or allergic reactions to thiamin 13. history of severe hypersensitivity reactions and/or anaphylaxis 14. clinically proven vitamin B1 deficiency 15. individuals taking regular vitamin B1 or multi-vitamin supplements who are not willing to comply with a 48-hour washout of these supplements before each kinetic visit 16. individuals who have taken vitamin B supplements or multi-vitamins in the past 2 days before kinetic visit 1 of each arm 17. poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it

Primary outcome measure(s)

Thiamin plasma concentrations expressed as Area under the Curve (AUC0-24 hours) — 24 hours
Difference in thiamin plasma concentrations expressed as Area under the Curve (AUC0-24 hours) between OCT1 wild type and OCT1 deficiency cohorts (Cohort 1 vs. Cohort 2) in each dose arm

Trial sites (1)

Facility	City	Region	Status
University Medicine Greifswald, Institute of Pharmacology	Greifswald	Mecklenburg-Vorpommern

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06122701 on ClinicalTrials.gov ↗ ← All trials in Germany