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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01DK108722-02 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Tufts University | OTHER |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| University of California, Davis | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Thiamine only | Active Comparator | 5mg thiamine tablet by mouth. This arm will be included in both Parts 1 and 2 of the study. |
|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathleen M Giacomini | University of California, San Francisco | Principal Investigator |
| Andrew S Greenberg | Tufts University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Jean Mayer USDA Human Nutrition Research Center on Aging | Boston | Massachusetts | 02111 | United States |
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7 subjects were randomized into one of two arms; each arm had two cycles (which were separated by a washout period of 5-14 days), and each cycle was three days in duration. During the Cycle 1, subjects were administered either a) 5 mg thiamine (n = 4) or b) 5 mg thiamine and 300 mg trimethoprim with 500 mL of water (n = 3). And during the Cycle 2, patients receive the other treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Thiamine Alone, Then Thiamine Co-administered With Trimethoprim | One day prior to each study visit, participants arrived to collect three thiamine-deficient meals. They were instructed to consume these meals throughout the day, abstaining from other food intake. After an overnight fast, participants returned for their scheduled visit. On the first visit, they received 5 mg thiamine in 500 mL of water. Following a 5-14 day washout period, they repeated the process, this time receiving a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water. |
| FG001 | Thiamine Co-administered With Trimethoprim, Then Thiamine Alone | One day prior to each study visit, participants arrived to collect three thiamine-deficient meals. They were instructed to consume these meals throughout the day, abstaining from other food intake. After an overnight fast, participants returned for their scheduled visit. On the first visit, they received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water. Following a 5-14 day washout period, they repeated the process, this time receiving a 5 mg thiamine in 500 mL of water. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cycle 1 |
| |||||||||||||
| Cycle 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Thiamine Alone, Thiamine Co-administered With Trimethoprim | Subjects were randomized into one of two arms; each arm had two cycles (which were separated by a washout period of 5-14 days), and each cycle was three days in duration. During the Cycle 1, subjects were administered either a) 5 mg thiamine (n = 4) or b) 5 mg thiamine and 300 mg trimethoprim with 500 mL of water (n = 3). And during the Cycle 2, patients receive the other treatment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | nM | The highest concentration of a thiamine observed in the blood plasma after drug administration |
|
Two cycles (which were separated by a washout period of 5-14 days) and each cycle was three days in duration.
The safty population included all participants who received the drug. The National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 should be used to assess and grade adverse event severity, including laboratory abnormalities judged to be clinically significant.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Thiamine Alone | Participants who received 5 mg thiamine in 500 mL of water in either the first or second cycle of the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kathleen Giacomini | University of California, San Francisco | 4155144363 | kathy.giacomini@ucsf.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 5, 2020 | Sep 9, 2024 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form: Main ICF Part 2 | Jan 18, 2022 | Sep 9, 2024 | ICF_001.pdf |
| ICF | No | No | Yes | Informed Consent Form: Screening ICF Part 2 | Jan 18, 2022 | Sep 9, 2024 | ICF_002.pdf |
| ICF | No | No | Yes | Informed Consent Form: Main ICF | Jan 18, 2022 | Sep 9, 2024 | ICF_003.pdf |
| ICF | No | No | Yes | Informed Consent Form: Screening ICF | Jan 18, 2022 | Sep 9, 2024 | ICF_004.pdf |
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| ID | Term |
|---|---|
| D001602 | Beriberi |
| D013832 | Thiamine Deficiency |
| ID | Term |
|---|---|
| D014804 | Vitamin B Deficiency |
| D001361 | Avitaminosis |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
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| ID | Term |
|---|---|
| D014295 | Trimethoprim |
| D013938 | Thymidine Monophosphate |
| D008687 | Metformin |
| D013831 | Thiamine |
| ID | Term |
|---|---|
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013942 | Thymine Nucleotides |
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Part 1: Three-arm randomized crossover study design Part 2: Two-arm randomized crossover study design
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|
| 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. |
|
|
| Vitamin B1 | Dietary Supplement | 5mg of thiamine will be given alone and in combination for both Parts 1 and 2 of the study. |
|
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| NOT COMPLETED |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kg |
|
| Height | Mean | Standard Deviation | cm |
|
| BMI | Mean | Standard Deviation | kg/m^2 |
|
| Baseline Thiamine (Thiamine arm) | Mean | Standard Deviation | nM |
|
| Baseline Thiamine (Trimethoprim + Thiamine arm) | Mean | Standard Deviation | nM |
|
Participants who received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water in either the first or second cycle of the study.
|
|
| Primary | 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). | Posted | Mean | Standard Deviation | nM*hr | 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. |
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 0 |
| 7 |
| EG001 | Thiamine Co-administered With Trimethoprim | Participants who received a combination of 5 mg thiamine and 300 mg trimethoprim with 500 mL of water in either the first or second cycle of the study. | 0 | 7 | 0 | 7 | 0 | 7 |
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| D009748 |
| Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D011742 |
| Pyrimidine Nucleotides |
| D003854 | Deoxyribonucleotides |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D001645 | Biguanides |
| D006146 | Guanidines |
| D000578 | Amidines |
| D009930 | Organic Chemicals |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D001393 | Azoles |