ClinicalTrials.gov
ClinicalTrials.gov Menu

Thiazolidinedione (TZD) on the Diabetic Retinopathy and Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01175486
Recruitment Status : Unknown
Verified June 2010 by Taipei Veterans General Hospital, Taiwan.
Recruitment status was:  Recruiting
First Posted : August 4, 2010
Last Update Posted : January 5, 2011
Sponsor:
Information provided by:
Taipei Veterans General Hospital, Taiwan

July 23, 2010
August 4, 2010
January 5, 2011
July 2010
December 2012   (Final data collection date for primary outcome measure)
  • Diabetic retinopathy [ Time Frame: 6 months ]
    The macular thickness changes
  • Diabetic nephropathy [ Time Frame: 6 months ]
    The changes in the level of urinary albumin-to-creatinine ratio
Same as current
Complete list of historical versions of study NCT01175486 on ClinicalTrials.gov Archive Site
  • Diabetic retinopathy [ Time Frame: 3 years ]
    Development of greater than moderate NPDR, clinically significant macular edema
  • Diabetic nephropathy [ Time Frame: 3 years ]
    The change of urine albumin excretion, estimated GFR change, progression to overt diabetic nephropathy.
Same as current
Not Provided
Not Provided
 
Thiazolidinedione (TZD) on the Diabetic Retinopathy and Nephropathy
The Effects of Thiazolidinedione on the Diabetic Retinopathy and Nephropathy

Objectives:

Thiazolidinediones (TZDs) are insulin sensitizers that decrease plasma glucose in type 2 diabetic patients. Thiazolidinediones can cause fluid retention and peripheral edema in diabetic patients, and the systematic fluid retention can be manifested as diabetic macular edema (DME). The overall goal of this study is to examine the effects of thiazolidinediones on the diabetic retinopathy and nephropathy.

Study design:

This is a prospective, randomized, open-labeled, controlled design to assess the effects thiozolidinediones on the diabetic retinopathy and nephropathy. The investigators will recruit 300 type 2 diabetic patients without significant retinopathy, nephropathy and cardiovascular disease. Inclusion criteria are type 2 diabetes, age between 30-80 years old, with microabluminuria, no significant retinopathy, on submaximal dose of sulphonylureas and metformin treatment, and A1C between 7-9%. Exclusion criteria are on insulin treatment, significant retinopathy and significant nephropathy. Patients with cardiovascular diseases, malignancy, pregnancy, in acute intercurrent illness, congestive heart failure, myocardial infarction, received PCI or CABG. All subjects will receive EKG and CXR before randomization.

These subjects will be randomized equally to 3 groups: acarbose, rosiglitazone and pioglitazone. The investigators will follow up for 6 months to investigate the short-term effects and 5 years to evaluate the long-term outcomes. The primary study end point of short-term study will be the macular thickness changes measured by optical coherence tomography, the changes in the level of urinary albumin-to-creatinine ratio, circulating metabolic parameters and adipocytokines during thiozolidinediones treatment. Secondary end point will be fasting blood glucose, A1C levels, development of clinically significant macular edema, serum creatinine change in patients with no history of diabetic retinopathy and nephropathy at baseline.

The primary study end point of long-term study will be the development of clinically significant macular edema and the time from the base-line visit to the first detection of overt nephropathy. Secondary end points include the development of greater than moderate NPDR, the time to the first event of the time from the base-line visit to a doubling of the serum creatinine concentration, end-stage renal disease, or death.

The effects of thiazolidinedione on the diabetic retinopathy and nephropathy:

Overall Goal and Specific Aims

The overall goal of this study is to examine the effects of thiazolidinediones on the diabetic retinopathy and nephropathy.

The specific aims are:

  1. To investigate the short-term effects of thiazolidinediones on the macular thickness measured by optical coherence tomography and the long-term effects of thiazolidinediones on the clinically significant macular edema and diabetic retinopathy documented by color photography and fluoroscein angiography.
  2. Short-term effects of thiazolidinediones on the change of urine albumin excretion and serum cardiovascular risk profiles and long-term effects of thiazolidinediones on the estimated GFR change and progression to overt diabetic nephropathy.

Objectives

Thiazolidinediones (TZDs) are insulin sensitizers that decrease plasma glucose in type 2 diabetic patients. Thiazolidinediones can cause fluid retention and peripheral edema in diabetic patients, and the systematic fluid retention can be manifested as diabetic macular edema (DME). The overall goal of this study is to examine the effects of thiazolidinediones on the diabetic retinopathy and nephropathy.

Study design

This is a prospective, randomized, open-labeled, controlled design to assess the effects thiozolidinediones on the diabetic retinopathy and nephropathy. The investigators will recruit 300 type 2 diabetic patients without significant retinopathy, nephropathy and cardiovascular disease. Inclusion criteria are type 2 diabetes, age between 30-80 years old, with microabluminuria, no significant retinopathy, on submaximal dose of sulphonylureas and metformin treatment, and A1C between 7-9%. Exclusion criteria are on insulin treatment, significant retinopathy and significant nephropathy. Patients with cardiovascular diseases, malignancy, pregnancy, in acute intercurrent illness, congestive heart failure, myocardial infarction, received PCI or CABG. All subjects will receive EKG and CXR before randomization.

These subjects will be randomized equally to 3 groups: acarbose, rosiglitazone and pioglitazone. The investigators will follow up for 6 months to investigate the short-term effects and 5 years to evaluate the long-term outcomes. The primary study end point of short-term study will be the macular thickness changes measured by optical coherence tomography, the changes in the level of urinary albumin-to-creatinine ratio, circulating metabolic parameters and adipocytokines during thiozolidinediones treatment. Secondary end point will be fasting blood glucose, A1C levels, development of clinically significant macular edema, serum creatinine change in patients with no history of diabetic retinopathy and nephropathy at baseline.

The primary study end point of long-term study will be the development of clinically significant macular edema and the time from the base-line visit to the first detection of overt nephropathy. Secondary end points include the development of greater than moderate NPDR, the time to the first event of the time from the base-line visit to a doubling of the serum creatinine concentration, end-stage renal disease, or death.

The investigators also monitor the long-term safety issue, such as congestive heart failure, myocardial infarction, any cardiovascular event, and fracture.

Expected Results

TZDs can decrease plasma glucose in type 2 diabetic patients, but the major side effects are able to cause fluid retention. This prospective study will be able to test whether thiozolidinediones causes macular edema and to evaluate whether thiozolidinediones delays onset of diabetic retinopathy. The investigators also will be able to find the changes in the level of urinary albumin-to-creatinine ratio, circulating metabolic parameters and adipocytokines between the treatment of TZDs and Acrbose. The investigators can compare the time from the base-line visit to the first detection of overt nephropathy, the time to the first event of the composite end point of the time from the base-line visit to a doubling of the serum creatinine concentration, end-stage renal disease, or death.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Diabetes
  • Drug: Actos (Pioglitazone)
    Actos 30 mg for 6 months
    Other Name: Pioglitazone
  • Drug: Acarbose
    Acarbose 50 mg tid for 6 months
    Other Name: Glucobay
  • Experimental: Actos
    Actos 30 mg for 6 months
    Intervention: Drug: Actos (Pioglitazone)
  • Active Comparator: Acarbose
    Acarbose 50mg tid for 6 months
    Intervention: Drug: Acarbose
Chen YH, Tarng DC, Chen HS. Renal Outcomes of Pioglitazone Compared with Acarbose in Diabetic Patients: A Randomized Controlled Study. PLoS One. 2016 Nov 3;11(11):e0165750. doi: 10.1371/journal.pone.0165750. eCollection 2016.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Unknown status
200
300
December 2015
December 2012   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Type 2 diabetes
  • Age between 30-80 years old
  • No significant nephropathy
  • No significant retinopathy
  • On submaximal dose of sulphonylureas and metformin treatment
  • A1C between 7-9%

Exclusion Criteria:

  • On insulin treatment
  • Significant retinopathy (greater than moderate non-proliferative retinopathy)
  • Significant nephropathy (overt proteinuria or serum Cr >1.50 mg/dL)
  • Malignancy
  • Pregnancy
  • Acute intercurrent illness
  • Congestive heart failure (CHF, according to New York heart Association, NYHA functional class III to IV)
  • Myocardial infarction, received PCI or CABG or liver cirrhosis
Sexes Eligible for Study: All
30 Years to 80 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Taiwan
 
 
NCT01175486
201004014IA
No
Not Provided
Not Provided
Tung-Ping Su, Chairman, Institutional Review Board, Taipei Veterans General Hospital,Taiwan
Taipei Veterans General Hospital, Taiwan
Not Provided
Principal Investigator: Harn-Shen Chen, MD, PhD Taipei Veterans General Hospital, Taiwan
Taipei Veterans General Hospital, Taiwan
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP