Prevention of Renal Complications of Diabetes With Thiamine

Diabetic Nephropathy Clinical Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01725412
• Other study ID #: Bio REB #12-59
• Status: Not yet recruiting
• Phase: Phase 4
• First received: November 8, 2012
• Last updated: November 9, 2012
• Start date: November 2012

Study information

• Verified date: November 2012
• Source: University of Saskatchewan
• Contact: Gudrun Caspar-Bell, MD
• Phone: 306 966-2044
• Email: Gudrun.casparbell[@]saskatoonhealthregion.ca
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 50 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Diabetic Nephropathy

Intervention

Dietary Supplement:
• Thiamine 300mg PO once daily

• placebo

Locations

Country	Name	City	State
Canada	Royal University Hospital	Saskatoon	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
University of Saskatchewan

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Urinary Thiamine Level			No
Other	Inflammatory Markers	E-selectin, Intercellular Adhesion Molecule 1, von Willebrand Factor, malondialdehyde, glutathione, homocysteine, isoprotein F21, advanced glycation endproducts, receptor for advanced glycation endproducts		No
Primary	Microabluminuria			No
Secondary	Serum Thiamine Level			No