Study of Alagebrium in Patients With Insulin-Dependent Type 1 Diabetes and Microalbuminuria

Study Overview
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Brief Summary
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Based upon the preclinical evidence in models of diabetic nephropathy under conditions approximating both type I and II diabetes, treatment with alagebrium appears to have favorable and advantageous effects on the biochemical, structural, pathological and functional hallmarks of diabetic nephropathy. The renoprotective effects of alagebrium in preclinical models favor the evaluation of this drug in patients with type I diabetes.

Detailed Description
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This study is a double-blind, randomized, placebo-controlled, parallel design trial enrolling 80 patients (2x40) with Type 1 diabetes and microalbuminuria. Patients will be randomized to either 200 mg Alagebrium twice daily or placebo for a period of 24 weeks after an 8 week run-in period. There will be a 8 week run-out period. All patients will receive ramipril during the entire study period. Efficacy measurements will be performed at baseline, at 12 weeks and at the end of the study. Measurements for albumin:creatinine ratio(mg/g), plasma renin level, collagen markers, AGE related markers and 24 hour blood pressure measurements will also be determined. A total of 9 visits will be performed during the entire study.

Official Title
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A Randomized, Placebo-Controlled Trial of Alagebrium in Patients With Insulin-Dependent Type 1 Diabetes and Microalbuminuria

Conditions
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Diabetes Mellitus, Type 1, Diabetic Nephropathy

Intervention / Treatment
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* Drug: Alagebrium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Insulin-dependent type 1 diabetes Age 18-65 years Diagnosis of established microalbuminuria Blood pressure <140 mm Hg, diastolic blood pressure <90 mm Hg HbA1c <10% Exclusion Criteria: Body mass index >40 kg/m2 Cardiovascular event within 6 months prior to screening History of acute myocardial infarction within 12 months prior to screening Serum creatinine >1.5 mg/dL Receiving chronic nonsteroidal anti-inflammatory therapy Receiving antihypertensive therapy except for angiotensin converting enzyme inhibitors or angiotensin receptor blockers Any significant systemic illnesses,medical conditions or abnormal laboratory values

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Alagebrium<br>* 200 mg bid<br>* Other names: ALT-711;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* bid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in albumin excretion rate (µg/min) |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Albumin:creatinine ratio(mg/g), plasma renin level, collagen markers, AGE related markers, 24 hour blood pressure determinations |  | 24 weeks |