How Does the Diabetes Drug, Pioglitazone, Reduce Protein Loss in the Urine?

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2009 by Christchurch Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Christchurch Hospital
ClinicalTrials.gov Identifier:
NCT00749047
First received: September 8, 2008
Last updated: September 15, 2009
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Pioglitazone
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Study on the Anti-proteinuric Effects of Pioglitazone in Patients With Type 2 Diabetes.

Resource links provided by NLM:


Further study details as provided by Christchurch Hospital:

Primary Outcome Measures:
  • Reduction in proteinuria [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction in non-fasting plasma glucose concentration [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: September 2008
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Open label arm
Drug: Pioglitazone
15-45 mg/day
Other Names:
  • Actos
  • Batch number A490463

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00749047

Locations
New Zealand
Christchurch Hospital
Christchurch, Canterbury, New Zealand, 8001
Sponsors and Collaborators
Christchurch Hospital
  More Information

No publications provided

Responsible Party: Dr Brett Shand, Lipid and Diabetes Research Group, Christchurch Hospital, New Zealand.
ClinicalTrials.gov Identifier: NCT00749047     History of Changes
Other Study ID Numbers: H6E-AY-O017
Study First Received: September 8, 2008
Last Updated: September 15, 2009
Health Authority: New Zealand: Health and Disability Ethics Committees

Keywords provided by Christchurch Hospital:
Pioglitazone
Open study
Proteinuria
Glomerular selectivity indices

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014