The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine

NCT03746106 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 130605R01DK108722-02
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

In Part 1, subjects will be administered thiamine, thiamine with metformin, and thiamine with trimethoprim. Part 2 will expand on Part 1 and subjects will be administered thiamine and thiamine with trimethoprim. The goal is to determine whether taking a drug and a vitamin together affects the body's ability to absorb, distribute, and eliminate thiamine (Vitamin B1).

Conditions

Vitamin B1 Deficiency; Thiamine Deficiency

Keywords

Drug-induced vitamin deficiency

Outcome Measures

Primary Outcomes (2)

• Maximum Concentration (Cmax) of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm

  Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. Cmax is determined by taking blood samples at various time points after drug administration and analyzing the thiamine concentration in plasma.

  The highest concentration of a thiamine observed in the blood plasma after drug administration

• Area Under the Curve From 0 to 24 (AUC0-24)Hours of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm

  Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle. AUC0-24 (Area Under the Curve from 0 to 24 hours) is a pharmacokinetic (PK) parameter that represents the total drug exposure in the body over a 24-hour period. It is calculated as the area under the plasma thiamine concentration vs. time curve (from time zero to 24 hours after drug administration).

  Plasma samples were collected at pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours post-dose for each cycle.

Study Arms (3)

Thiamine only

ACTIVE COMPARATOR

5mg thiamine tablet by mouth. This arm will be included in both Parts 1 and 2 of the study.

Dietary Supplement: Vitamin B1

Trimethporim + thiamine combination

EXPERIMENTAL

5mg thiamine tablet and 300mg trimethoprim tablet by mouth. This arm will be included in both Parts 1 and 2 of the study.

Drug: Trimethoprim; Dietary Supplement: Vitamin B1

Metformin + thiamine combination

EXPERIMENTAL

5mg thiamine tablet and 1000mg metformin tablet by mouth. This arm will be included in only Part 1 of the study.

Drug: Metformin; Dietary Supplement: Vitamin B1

Interventions

Trimethoprim DRUG

300mg of trimethoprim will be given in combination with 5mg thiamine and compared to 5mg thiamine only for both Parts 1 and 2 of the study.

Also known as: Primsol

Trimethporim + thiamine combination

Metformin DRUG

1000mg of metformin will be given in combination with 5mg thiamine and compared to 5mg thiamine only in Part 1 of the study.

Also known as: Glucophage

Metformin + thiamine combination

Vitamin B1 DIETARY_SUPPLEMENT

5mg of thiamine will be given alone and in combination for both Parts 1 and 2 of the study.

Also known as: Thiamine

Metformin + thiamine combination; Thiamine only; Trimethporim + thiamine combination

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between the ages of 18-65 years old.
• Eats a wide variety of food and willing to consume study diet (i.e. not on a specific diet such as Atkins, Fodmap, etc.).
• Written informed consent obtained from the subject and ability for subject to comply with the requirements of the study.

You may not qualify if:

• Subjects who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• Self-reported severe food allergies or diet restrictions (vegans, vegetarians, Atkins, Fodmap, etc.) that would prevent consumption of study diets.
• Subjects with extreme obesity (BMI \> 35).
• Subjects who are smokers or have smoked in the past year and/or have smoked or ingested THC/marijuana in the past week, or who are unwilling to comply with a 1-week washout.
• Subjects with any disease affecting or impairing the function of the liver, kidney or heart.
• Subjects with moderate to severe hypertension.
• Subjects with diabetes mellitus, hyperthyroidism, hypothyroidism, cardiovascular disease, glaucoma.
• Subjects with gastrointestinal disease, gastrointestinal disorder, or gastrointestinal surgery.
• Subjects with known infection with HIV, Hepatitis B (HBsAg) or Hepatitis C (no laboratory diagnostics concerning these diseases will be performed within the present study. Volunteers who are cured of past HepC infection are eligible to participate with doctor's approval letter).
• Alcohol use on average \> 2 servings/day or \> 14 servings/wk (Serving size: 12oz beer/4oz wine/2oz hard liquor) or self-reported binge drinking.
• Subjects that are on vitamin B supplements or multi-vitamins or who have taken vitamin B supplements or multi-vitamins in the past 30 days, or are not willing to comply with a 30-day washout of vitamin B supplements.
• Subjects with possible folate deficiency.
• Subjects taking any other clinically significant drugs as judged by the investigator.
• Subjects with a condition, disease, or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
• Female subjects undergoing treatment for infertility or hormone replacement therapy (Volunteers using hormonal birth control will not be excluded).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Tufts University: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• University of California, Davis: collaborator

Study Sites (1)

Jean Mayer USDA Human Nutrition Research Center on Aging

Boston, Massachusetts, 02111, United States

Location

MeSH Terms

Conditions

Beriberi; Thiamine Deficiency

Interventions

Trimethoprim; Thymidine Monophosphate; Metformin; Thiamine

Condition Hierarchy (Ancestors)

Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymine Nucleotides; Pyrimidine Nucleotides; Deoxyribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles

Results Point of Contact

• Title: Dr. Kathleen Giacomini
• Organization: University of California, San Francisco

kathy.giacomini@ucsf.edu

4155144363

Study Officials

• Kathleen M Giacomini

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Andrew S Greenberg

  Tufts University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Part 1: Three-arm randomized crossover study design Part 2: Two-arm randomized crossover study design

Study Record Dates

• First Submitted: November 8, 2018
• First Posted: November 19, 2018
• Study Start: January 28, 2019
• Primary Completion: August 10, 2023
• Study Completion: August 10, 2023
• Last Updated: January 3, 2025
• Results First Posted: January 3, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)