Dose-dependent Kinetics of Thiamin in Healthy Volunteers With and Without Functional OCT1 Hepatic Transporters — THIAMO-1  

Healthy Clinical Trial

Official title: Cross-over Randomized Study to Determine Dose-dependent Kinetics of Thiamin in Healthy Volunteers With and Without Functional OCT1 Hepatic Transporters

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial Description

The study is designed as a 4-arm cross-over, open-label, randomized single oral dose comparison (5 mg, 10 mg, 50 mg, and 200 mg thiamin). A fifth arm applying thiamin intravenously with a dose selected based on results from the four oral arms is also planned.

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 analyzing the four oral arms, we will administer a single i.v. dose of thiamin in arm 5 at a later time point. The dosage will be determined after analyzing the results of orally administered thiamin in arm 2 to 4.

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. At baseline, 2x 2.7 ml EDTA blood samples will be collected for DNA isolation if the particular volunteer has not had a genotypical validation in another study of our Institute.

The total amount of blood collected for each participant is 456 ml at eight kinetic visits and 10 ml at the Screening.

After intake of the thiamin solution, participants will drink 100 ml of sparkling water every hour to stimulate gastrointestinal peristalsis. After 4 hours the participants will be served a meal low in thiamin content. Urine will be collected during the first 10 hours after thiamin administration. Monitoring of blood pressure and heart rate will take place for the first 4 hours after administration. Volunteers will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 hours after administration. ;

Related Conditions & MeSH terms

• Healthy

• NCT number: NCT06122701
• Study type: Interventional
• Source: University Medicine Greifswald
• Contact: Stefan Engeli, Prof.
• Phone: +49 3834865633
• Email: stefan.engeli@med.uni-greifswald.de
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 20, 2023
• Completion date: December 2024