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

Launched by UNIVERSITY MEDICINE GREIFSWALD · Nov 7, 2023

Keywords

ClinConnect Summary

The study is designed as a 5-arm cross-over, open-label, randomized single oral dose comparison (5 mg, 10 mg, 50 mg, and 200 mg thiamin). A fifth arm includes applying 5 mg thiamin intravenously.

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. These four arms will be put into practice at the same time with each participant completing all four arms in random order with a wash-out period of at least one week between each arm.

After ...

Gender

ALL

Eligibility criteria

• 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