Prevention of Renal Complications of Diabetes With Thiamine

Phase 4

• Conditions: Diabetic Nephropathy
• Interventions: Dietary Supplement: Thiamine 300mg PO once daily; Dietary Supplement: placebo

• Registration Number: NCT01725412
• Lead Sponsor: University of Saskatchewan

Brief Summary

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.

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 Timeline

• Status Verified: 2012-11
• Study Start: 2012-11
• Study First Submitted: 2012-11-08
• Study First Submitted QC: 2012-11-09
• Last Update Submitted: 2012-11-09
• Study First Posted: 2012-11-12
• Last Update Posted: 2012-11-12
• Primary Completion: 2013-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Thiamine Supplementation	Thiamine 300mg PO once daily	-
Placebo	placebo	-

Primary Outcome Measures

Name	Time	Method
Microabluminuria

Secondary Outcome Measures

Name	Time	Method
Serum Thiamine Level

Trial Locations

Locations (1)

Royal University Hospital; 🇨🇦 Saskatoon, Saskatchewan, Canada