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.
Trial 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. Read more about this study
- 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.
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- 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
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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Tufts University, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of California, Davis
- Responsible party
- Sponsor
- Investigators
- Kathleen M Giacomini, Principal investigator, University of California, San FranciscoAndrew S Greenberg, Principal investigator, Tufts University
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.
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).
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.
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
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
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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?
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.