How Does the Diabetes Drug, Pioglitazone, Reduce Protein Loss in the Urine?
Information source: Christchurch Hospital
Information obtained from ClinicalTrials.gov on February 12, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Diabetes Mellitus, Type 2
Intervention: Pioglitazone (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: Christchurch Hospital Overall contact:
Brett I Shand, PhD, Phone: 64 3 3643640, Ext: 81372, Email: brett.shand@cdhb.govt.nz
Summary
Pioglitazone is an insulin sensitising drug used in the treatment of patients with type 2
diabetes. In addition to its blood sugar lowering effect, pioglitazone also has a number of
other beneficial effects, one of which is to reduce the loss of protein in the urine. The
mechanism of this protein "sparing effect" of pioglitazone is not fully understood. The
proposed study will investigate whether pioglitazone has beneficial effects on the filtration
characteristics of filters in the kidney that are responsible for retaining protein in the
body. The effect of pioglitazone on the size of the pores in the filters and also the
electrostatic charge barriers that surround these pores will be investigated. The clinical
study will involve 12 patients with type 2 diabetes with minimal urine protein loss, taking
low dose pioglitazone for 3 months. Blood and urine samples will be collected at the
beginning, mid point and end of the study and used to measure the concentration of specific
proteins of different size and electrostatic charge. This data will be used to identify and
characterise changes in the filtration properties of the kidney filters during the study.
Clinical Details
Official title: A Study on the Anti-Proteinuric Effects of Pioglitazone in Patients With Type 2 Diabetes.
Study design: Basic Science, Open Label, Uncontrolled, Single Group Assignment
Primary outcome: Reduction in proteinuria
Secondary outcome: Reduction in non-fasting plasma glucose concentration
Detailed description:
In addition to their insulin sensitising action, thiazolidinediones (TZDs) have beneficial
effects on vascular function. These include a decrease in proteinuria and amelioration of
diabetic nephropathy. Although the anti-proteinuric effect of TZDs is well established the
mechanism(s) underlying these changes has yet to be determined. Possible mechanisms include
altered renal haemodynamics, maintenance of anionic electrostatic filtration barriers in the
glomerular basement membrane and pleiotropic effects.
The target of TZDs, the peroxisome proliferator-activated receptors (PPARs), directly
modulate vessel wall function. The kidney differentially expresses all PPAR isoforms and
there is evidence that TZDs have pleiotropic effects in the kidney over and above their
metabolic and haemodynamic actions. These effects include a direct action on cultured
mesangial cells, inhibition of in vivo mesangial expansion, reduction in podocyte injury,
and decreased production of type IV collagen and urinary endothelin-1 levels in early stage
diabetic nephropathy.
Glomerular ultrafiltration of plasma proteins is governed by the size of the filtration pores
and the extent of anionic sites in the basement membrane and podocyte slit pore junction. It
is possible that the anti-proteinuric effect of TZDs is attributable to an increase in size
and/or charge selectivity in the glomerular filtration barrier. A Medline search showed there
have been no studies on the effect of TZDs on protein ultrafiltration. The aim of the
proposed study is to measure urinary protein size and charge selectivity in patients with
early stage diabetic nephropathy before and after treatment with the TZD, pioglitazone.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Diabetes mellitus, Type 2
- Age 18-70 yrs
Exclusion Criteria:
- Overt proteinuria (urine albumin: creatinine ratio >10. 0
- Plasma creatinine 0. 15 mmol/L
- HbA1c >10%
- Hear failure Class III or IV
- Peripheral oedema
- Abnormal liver function (serum AST >2. 5 times upper limit of normal)
- Pregnancy or breastfeeding
- History of urinary tract infections
- Serious concomitant disorder
Locations and Contacts
Brett I Shand, PhD, Phone: 64 3 3643640, Ext: 81372, Email: brett.shand@cdhb.govt.nz
Christchurch Hospital, Christchurch, Canterbury 8001, New Zealand; Recruiting
Brett I Shand, PhD, Phone: 64 3 3640640, Ext: 81372, Email: brett.shand@cdhb.govt.nz
Russell S Scott, FRACP, Phone: 64 3 3640640, Ext: 80449, Email: russell.scott@cdhb.govt.nz
Brett I Shand, BSc, PhD, Principal Investigator
Additional Information
Starting date: September 2008
Ending date: December 2009
Last updated: September 8, 2008
|
