Prevention of Renal Complications of Diabetes With Thiamine

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by University of Saskatchewan
Sponsor:
Information provided by (Responsible Party):
Gudrun Caspar-Bell, University of Saskatchewan
ClinicalTrials.gov Identifier:
NCT01725412
First received: November 8, 2012
Last updated: November 9, 2012
Last verified: November 2012
  Purpose

Thiamine is a key component in the creation of physiologic anti-inflammatory mediators. Serum thiamine stores have been found to be deficient in diabetic patients. Thiamine deficiency may be a key pathological mechanism of inflammation that results in diabetic kidney and retinal injury. The investigators hypothesize that the repletion of a patient's thiamine by oral supplementation may result in reduced inflammation, and therefore reduced kidney injury.


Condition Intervention Phase
Diabetic Nephropathy
Dietary Supplement: Thiamine 300mg PO once daily
Dietary Supplement: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by University of Saskatchewan:

Primary Outcome Measures:
  • Microabluminuria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Serum Thiamine Level [ Designated as safety issue: No ]

Other Outcome Measures:
  • Urinary Thiamine Level [ Designated as safety issue: No ]
  • Inflammatory Markers [ Designated as safety issue: No ]
    E-selectin, Intercellular Adhesion Molecule 1, von Willebrand Factor, malondialdehyde, glutathione, homocysteine, isoprotein F21, advanced glycation endproducts, receptor for advanced glycation endproducts


Estimated Enrollment: 40
Study Start Date: November 2012
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thiamine Supplementation Dietary Supplement: Thiamine 300mg PO once daily
Placebo Comparator: Placebo Dietary Supplement: placebo

Detailed Description:

Thiamine (vitamin B1) is a water-soluble vitamin. It is absorbed from the gastrointestinal tract and taken up into tissues by transport proteins and converted to thiamine pyrophosphate (TPP) by thiamine pyrophosphokinase (TPPK). TPP is a co-factor of pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase and transketolase (TKT)—enzymes involved in the metabolism of glucose.

Various transport proteins are involved in the transport of thiamine monophosphate (TMP) and TPP across membranes. These include thiamine transported isoform-1 (THTR1) and thiamine transporter isoform-2 (THTR2), reduced folate carrier-1 (RFC-1), which transports TMP and TPP across cell plasma membranes and the mitochondrial TPP transporter (mTHTR). Thiamine and TMP/TPP transporters may have abnormal expression in diabetes. Increased THTR1 levels are found in red blood cells (RBCs) and mononuclear leucocytes of patients with diabetes compared to those of healthy subjects. RBC precursors and leucocytes appeared to up-regulate THTR1 expression in response to decreased thiamine availability. In the presence of hyperglycemia, renal tubular epithelial cells, by contrast, have decreased expression. In both experimental models of diabetes and in human diabetics increased clearance of thiamine has been demonstrated. This precedes the development of microalbuminuria. Patients with microalbuminuria and early decline in glomerular filtration rate had higher fractional excretion of thiamine compared to patients with stable renal function.

Thiamine supplementation in STZ- diabetic mice prevented the development of microalbuminuria, decreasing urinary albumin excretion (UAE) by approximately 80%. In addition thiamine supplementation prevented diuresis and glycosuria. Human studies are limited but in one placebo controlled study the thiamine group showed a significant decrease in microalbuminuria in diabetic patients on thiamine.

  Eligibility

Ages Eligible for Study:   30 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • with a diagnosis of Type II diabetes which has been present for at least 5 years,
  • persistent microalbuminuria (30-299 mg/24 h),
  • HbA1c ≤ 8%, and
  • BMI 19-40 kg/m2.

Exclusion Criteria:

  • significant comorbidities,
  • "deficient renal function" known allergy or intolerance to thiamine,
  • use of thiamine supplements,
  • participation in an interventional study within 30 days,
  • recipients of renal and/or pancreatic transplant and
  • women who were pregnant or breast feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01725412

Contacts
Contact: Gudrun Caspar-Bell, MD 306 966-2044 Gudrun.casparbell@saskatoonhealthregion.ca
Contact: Benjamin M Sehmer, MB 306 261 3932 benjamin.sehmer@usask.ca

Locations
Canada, Saskatchewan
Royal University Hospital Recruiting
Saskatoon, Saskatchewan, Canada, S7K 0M7
Contact: Gudrun Caspar-Bell         
Sponsors and Collaborators
University of Saskatchewan
Investigators
Principal Investigator: Dr. Gudrun Caspar-Bell, MD University of Saskatchewan
  More Information

No publications provided

Responsible Party: Gudrun Caspar-Bell, Endocrinologist, University of Saskatchewan
ClinicalTrials.gov Identifier: NCT01725412     History of Changes
Other Study ID Numbers: Bio REB #12-59
Study First Received: November 8, 2012
Last Updated: November 9, 2012
Health Authority: Canada: Ethics Review Committee

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Thiamine
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014