Thiazolidinedione (TZD) on the Diabetic Retinopathy and Nephropathy

Diabetes Clinical Trial

Official title:

The Effects of Thiazolidinedione on the Diabetic Retinopathy and Nephropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01175486
• Other study ID #: 201004014IA
• Status: Recruiting
• Phase: Phase 4
• First received: July 23, 2010
• Last updated: January 4, 2011
• Start date: July 2010
• Est. completion date: December 2015

Study information

• Verified date: June 2010
• Source: Taipei Veterans General Hospital, Taiwan
• Contact: Harn-Shen Chen, MD, PhD
• Phone: 886-2-28757515
• Email: chenhs[@]vghtpe.gov.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2015
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes
• Diabetic Retinopathy
• Kidney Diseases
• Retinal Diseases

Intervention

Drug:
• Actos (Pioglitazone)
Actos 30 mg for 6 months
• Acarbose
Acarbose 50 mg tid for 6 months

Locations

Country	Name	City	State
Taiwan	Taipei Veterans General Hospital, Taiwan	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taipei Veterans General Hospital, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diabetic retinopathy	The macular thickness changes	6 months	Yes
Primary	Diabetic nephropathy	The changes in the level of urinary albumin-to-creatinine ratio	6 months	Yes
Secondary	Diabetic retinopathy	Development of greater than moderate NPDR, clinically significant macular edema	3 years	Yes
Secondary	Diabetic nephropathy	The change of urine albumin excretion, estimated GFR change, progression to overt diabetic nephropathy.	3 years	Yes