Vitamin B1 DeficiencyPhase 4NCT03746106

The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine

A Phase 4 study testing Trimethoprim, Metformin and Vitamin B1 in people with Vitamin B1 Deficiency and Thiamine Deficiency, run by University of California, San Francisco at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Vitamin B1 Deficiency, Thiamine Deficiency
What is being tested?: Trimethoprim, Metformin and Vitamin B1
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 7 participants
Where: 1 siteUnited States
Study dates: 28 Jan 2019to 10 Aug 2023
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 19Show fewer

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).
Subjects who have taken antimalarials in the past 60 days.
Participating in another research study while participating in this research study.
Non-English speaking
Subjects with abnormal laboratory results at screening as judged by the investigator or study physician.

Trial locations and contacts

1 site in 1 country.

United States1 site

Jean Mayer USDA Human Nutrition Research Center on Aging
Boston, Massachusetts, 02111

Other trials in United States

About this study

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).

Read the detailed description

Thiamine is an essential vitamin meaning humans must consume thiamine from their diet in order to stay healthy. Low thiamine levels can lead to adverse events. Thiamine is absorbed in the intestine by a transporter protein. This is made by the SLC19A3 gene. The SLC19A3 gene provides instructions for making the thiamine transporter protein, which moves thiamine into cells. Certain drugs, like metformin and trimethoprim, have been shown to interrupt function of the SLC19A3 gene.

Metformin is a first-line therapy for patients with Type 2 diabetes and is associated with improvements in diabetic complications. Trimethoprim is an anti-bacterial drug that is often prescribed to treat infections such as urinary tract infections. At different phases of this study, participants will be administered thiamine, thiamine with metformin, and/or thiamine with trimethoprim to determine whether taking a drug and a vitamin together affects the body's ability to absorb, distribute, and eliminate thiamine. The levels of thiamine in the participants' blood and urine will be measured before and after taking thiamine or thiamine in combination with metformin and/or trimethoprim.

Conditions: Vitamin B1 Deficiency, Thiamine Deficiency
Being tested: Trimethoprim, Metformin, Vitamin B1
Keywords: Drug-induced vitamin deficiency
Medical subject headings: Beriberi, Thiamine Deficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TrimethoprimDrug
Also called Primsol
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.
MetforminDrug
Also called Glucophage
1000mg of metformin will be given in combination with 5mg thiamine and compared to 5mg thiamine only in Part 1 of the study.
Vitamin B1Dietary supplement
Also called Thiamine
5mg of thiamine will be given alone and in combination for both Parts 1 and 2 of the study.

Study groups in NCT03746106
Study group	Role	What they receive
Thiamine only	Active comparator	5mg thiamine tablet by mouth. This arm will be included in both Parts 1 and 2 of the study. Receives: 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. Receives: 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. Receives: Drug: Metformin; Dietary Supplement: Vitamin B1

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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).
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 Jan 201910 Aug 2023

First posted19 Nov 2018
Study start28 Jan 2019
Primary completion10 Aug 2023
Study completion10 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Vitamin B1 DeficiencyStudies of the same condition, open and under way.
More trials run by University of California, San FranciscoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Model description: Part 1: Three-arm randomized crossover study design Part 2: Two-arm randomized crossover study design
Masking: None (open label)
Enrolment: 7 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03746106
Sponsor's protocol ID: 13060
Other IDs: 5R01DK108722-02
Status last verified: Dec 2024
First submitted: 8 Nov 2018
Last updated: 3 Jan 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine
ClinicalTrials.gov ID: NCT03746106
Acronym / sponsor ID: 13060
Conditions: Vitamin B1 Deficiency, Thiamine Deficiency
Keywords: Drug-induced vitamin deficiency
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 7 participants (actual)
Lead sponsor: University of California, San FranciscoUniversity, hospital or other
Collaborators: Tufts University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of California, Davis
Study start: 28 Jan 2019 (actual)
Primary completion: 10 Aug 2023 (actual)
Study completion: 10 Aug 2023 (actual)
First posted: 19 Nov 2018 (actual)
Results: Posted 3 Jan 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3
Model description: Part 1: Three-arm randomized crossover study design Part 2: Two-arm randomized crossover study design

Arm	Type	Receives
Thiamine only	Active comparator	Dietary Supplement: Vitamin B15mg thiamine tablet by mouth. This arm will be included in both Parts 1 and 2 of the study.
Trimethporim + thiamine combination	Experimental	Drug: Trimethoprim, Dietary Supplement: Vitamin B15mg thiamine tablet and 300mg trimethoprim tablet by mouth. This arm will be included in both Parts 1 and 2 of the study.
Metformin + thiamine combination	Experimental	Drug: Metformin, Dietary Supplement: Vitamin B15mg thiamine tablet and 1000mg metformin tablet by mouth. This arm will be included in only Part 1 of the study.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (19 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TrimethoprimAlso: Primsol300mg 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.	Drug	Trimethporim + thiamine combination
MetforminAlso: Glucophage1000mg of metformin will be given in combination with 5mg thiamine and compared to 5mg thiamine only in Part 1 of the study.	Drug	Metformin + thiamine combination
Vitamin B1Also: Thiamine5mg of thiamine will be given alone and in combination for both Parts 1 and 2 of the study.	Dietary supplement	Metformin + thiamine combination, Thiamine only, Trimethporim + thiamine combination

Primary outcome

Maximum Concentration (Cmax) of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm
Time frame: The highest concentration of a thiamine observed in the blood plasma 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. Cmax is determined by taking blood samples at various time points after drug administration and analyzing the thiamine concentration in plasma.
Area Under the Curve From 0 to 24 (AUC0-24)Hours of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm
Time frame: 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.
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).

Results and safety

Results posted to the registry on 3 Jan 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Thiamine Alone, Then Thiamine Co-administered With Trimethoprim	4	4
Thiamine Co-administered With Trimethoprim, Then Thiamine Alone	3	3

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

Time frame: The highest concentration of a thiamine observed in the blood plasma after drug administration. Mean (Standard Deviation). Unit: nM

Measure	Thiamine Alone n = 7	Thiamine Co-administered With Trimethoprim n = 7
Value	15 (9.5)	32 (22)

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

Time frame: 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.. Mean (Standard Deviation). Unit: nM*hr

Measure	Thiamine Alone n = 7	Thiamine Co-administered With Trimethoprim n = 7
Value	50 (30)	189 (138)

Adverse events

Time frame: Two cycles (which were separated by a washout period of 5-14 days) and each cycle was three days in duration.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Thiamine Alone	0 of 7 (0%)	0 of 7 (0%)	0 of 7
Thiamine Co-administered With Trimethoprim	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kathleen M Giacomini principal investigator

University of California, San Francisco

Andrew S Greenberg principal investigator

Tufts University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Trimethoprim, Metformin and Vitamin B1 in people with Vitamin B1 Deficiency and Thiamine Deficiency, run by University of California, San Francisco at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Concentration (Cmax) of Thiamine in Plasma Between the Combination Arm(s) and Single Agent Arm (time frame: The highest concentration of a thiamine observed in the blood plasma after drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03746106.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2025; AzTrials last refreshed its copy on 8 Nov 2026.