Prevention of Renal Complications of Diabetes With Thiamine

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.

Study Overview

• Status: Unknown
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: Thiamine 300mg PO once daily

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Gudrun Caspar-Bell, MD; Phone Number: 306 966-2044; Email: Gudrun.casparbell@saskatoonhealthregion.ca
• Study Contact Backup: Name: Benjamin M Sehmer, MB; Phone Number: 306 261 3932; Email: benjamin.sehmer@usask.ca

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7K 0M7
      • Royal University Hospital
      • Contact: Gudrun Caspar-Bell

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Dietary supplement: placebo
EXPERIMENTAL: Thiamine Supplementation	Dietary supplement: Thiamine 300mg PO once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Microabluminuria

Secondary Outcome Measures

Outcome Measure
Serum Thiamine Level

Other Outcome Measures

Outcome Measure	Measure Description
Urinary Thiamine Level
Inflammatory Markers	E-selectin, Intercellular Adhesion Molecule 1, von Willebrand Factor, malondialdehyde, glutathione, homocysteine, isoprotein F21, advanced glycation endproducts, receptor for advanced glycation endproducts

Collaborators and Investigators

• Sponsor: University of Saskatchewan
• Investigators: Principal Investigator: Dr. Gudrun Caspar-Bell, MD, University of Saskatchewan

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ANTICIPATED): June 1, 2013

Study Registration Dates

• First Submitted: November 8, 2012
• First Submitted That Met QC Criteria: November 9, 2012
• First Posted (ESTIMATE): November 12, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 12, 2012
• Last Update Submitted That Met QC Criteria: November 9, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetic Nephropathies; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: Bio REB #12-59