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Trial record 7 of 22 for:    "Beriberi"

The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine

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ClinicalTrials.gov Identifier: NCT03746106
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : February 6, 2019
Sponsor:
Collaborators:
Tufts University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, Davis
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
Subjects will be administered thiamine, thiamine with metformin, and thiamine with trimethoprim to determine whether taking a drug and a vitamin together affects the body's ability to absorb, distribute, and eliminate thiamine (Vitamin B1).

Condition or disease Intervention/treatment Phase
Vitamin B1 Deficiency Thiamine Deficiency Drug: Trimethoprim Drug: Metformin Dietary Supplement: Vitamin B1 Phase 4

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 three-cycle study, participants will be administered thiamine, thiamine with metformin, 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 trimethoprim.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Three-arm randomized crossover study design.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine
Actual Study Start Date : January 28, 2019
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019


Arm Intervention/treatment
Active Comparator: Thiamine only
5mg thiamine tablet by mouth.
Dietary Supplement: Vitamin B1
5mg of thiamine will be given alone and in combination
Other Name: Thiamine

Experimental: Trimethporim + thiamine combination
5mg thiamine tablet and 300mg trimethoprim tablet by mouth.
Drug: Trimethoprim
300mg of trimethoprim will be given in combination with 5mg thiamine and compared to 5mg thiamine only

Dietary Supplement: Vitamin B1
5mg of thiamine will be given alone and in combination
Other Name: Thiamine

Experimental: Metformin + thiamine combination
5mg thiamine tablet and 1000mg metformin tablet by mouth.
Drug: Metformin
1000mg of metformin will be given in combination with 5mg thiamine and compared to 5mg thiamine only

Dietary Supplement: Vitamin B1
5mg of thiamine will be given alone and in combination
Other Name: Thiamine




Primary Outcome Measures :
  1. Effect of SLC19A3 inhibitors on the absorption and distribution of thiamine as measured by the change in AUC between the thiamine and inhibitor (combination) arms and thiamine (single agent) arm. [ Time Frame: As determined by blood/urine levels taken over the course of 3 cycles (each cycle is 3 days with a 5-14 day washout in between cycles) ]

Secondary Outcome Measures :
  1. Investigate metabolic signatures reflecting the activity of TPP-dependent enzymes by comparing levels of individual metabolites and metabolic ratios after the administration of thiamine or a combination of the thiamine and SLC19A3 inhibitor. [ Time Frame: As determined by blood/urine levels taken over the course of 3 cycles (each cycle is 3 days with a 5-14 day washout in between cycles) ]
  2. Effect of genetic variants of thiamine transporters on thiamine disposition and absorption. [ Time Frame: As determined by blood/urine levels taken over the course of 3 cycles (each cycle is 3 days with a 5-14 day washout in between cycles) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Subjects who are pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
  2. Self-reported severe food allergies or diet restrictions (vegans, vegetarians, Atkins, Fodmap, etc.) that would prevent consumption of study diets.
  3. Subjects with extreme obesity (BMI > 35).
  4. 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.
  5. Subjects with any disease affecting or impairing the function of the liver, kidney or heart.
  6. Subjects with moderate to severe hypertension.
  7. Subjects with diabetes mellitus, hyperthyroidism, hypothyroidism, cardiovascular disease, glaucoma.
  8. Subjects with gastrointestinal disease, gastrointestinal disorder, or gastrointestinal surgery.
  9. 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).
  10. 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.
  11. 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.
  12. Subjects with possible folate deficiency.
  13. Subjects taking any other clinically significant drugs as judged by the investigator.
  14. 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.
  15. Female subjects undergoing treatment for infertility or hormone replacement therapy (Volunteers using hormonal birth control will not be excluded).
  16. Subjects who have taken antimalarials in the past 60 days.
  17. Participating in another research study while participating in this research study.
  18. Non-English speaking
  19. Subjects with abnormal laboratory results at screening as judged by the investigator or study physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03746106


Contacts
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Contact: Andrew S Greenberg 617-556-3144 Andrew.greenberg@tufts.edu
Contact: Kim Vo 617-636-2842 kvo@tuftsmedicalcenter.org

Locations
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United States, Massachusetts
Jean Mayer USDA Human Nutrition Research Center on Aging Recruiting
Boston, Massachusetts, United States, 02111
Contact: Kim T Vo    617-636-2842    kvo@tuftsmedicalcenter.org   
Principal Investigator: Andrew S Greenberg, MD         
Sponsors and Collaborators
University of California, San Francisco
Tufts University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, Davis
Investigators
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Principal Investigator: Kathleen M Giacomini University of California, San Francisco
Principal Investigator: Andrew S Greenberg Tufts University

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT03746106     History of Changes
Other Study ID Numbers: 13060
5R01DK108722-02 ( U.S. NIH Grant/Contract )
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University of California, San Francisco:
Drug-induced vitamin deficiency

Additional relevant MeSH terms:
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Thiamine Deficiency
Beriberi
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamins
Thiamine
Metformin
Trimethoprim
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Hypoglycemic Agents
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Dyskinesia Agents
Cytochrome P-450 CYP2C8 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Vitamin B Complex