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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

Tracking Information
First Submitted Date  ICMJE November 8, 2018
First Posted Date  ICMJE November 19, 2018
Last Update Posted Date February 6, 2019
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03746106 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2018)
  • 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) ]
  • 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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine
Official Title  ICMJE The Effect of SLC19A3 Inhibition on the Pharmacokinetics of Thiamine
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).
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Three-arm randomized crossover study design.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Vitamin B1 Deficiency
  • Thiamine Deficiency
Intervention  ICMJE
  • Drug: Trimethoprim
    300mg of trimethoprim will be given in combination with 5mg thiamine and compared to 5mg thiamine only
  • 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
Study Arms  ICMJE
  • Active Comparator: Thiamine only
    5mg thiamine tablet by mouth.
    Intervention: Dietary Supplement: Vitamin B1
  • Experimental: Trimethporim + thiamine combination
    5mg thiamine tablet and 300mg trimethoprim tablet by mouth.
    Interventions:
    • Drug: Trimethoprim
    • Dietary Supplement: Vitamin B1
  • Experimental: Metformin + thiamine combination
    5mg thiamine tablet and 1000mg metformin tablet by mouth.
    Interventions:
    • Drug: Metformin
    • Dietary Supplement: Vitamin B1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 14, 2018)
7
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2019
Estimated Primary Completion Date October 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Andrew S Greenberg 617-556-3144 Andrew.greenberg@tufts.edu
Contact: Kim Vo 617-636-2842 kvo@tuftsmedicalcenter.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03746106
Other Study ID Numbers  ICMJE 13060
5R01DK108722-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of California, San Francisco
Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE
  • Tufts University
  • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
  • University of California, Davis
Investigators  ICMJE
Principal Investigator: Kathleen M Giacomini University of California, San Francisco
Principal Investigator: Andrew S Greenberg Tufts University
PRS Account University of California, San Francisco
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP