Controlled Study to Evaluate Efficacy and Safety of α-KA Tab With Low Protein Diet (LPD) in Delaying the Progress of Type 2 Diabetic Nephropathy (DN)

A Multicenter, Randomized, Open-label, Parallel-group, Diabetic Diet-controlled Study to Evaluate the Efficacy and Safety of Compound α-Keto Acid Tablet in Combination With LPD in Delaying the Progress of Type 2 Diabetic Nephropathy

Current expert opinion based consensus guidelines recommend usage of α-Keto analogues of essential amino acids in the diet of diabetic nephropathy patients, along with restricted protein diets. This study is designed to explore whether alpha-Keto Acid supplementation with low protein diet will retard progression of type 2 diabetic nephropathy and also to assess effects of such supplemented diets on nutritional and other parameters in this patient group.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Drug: Ketosteril®; Other: diabetic diet

Detailed Description

Diabetic nephropathy is the most common cause for end-stage renal disease (ESRD) in Europe and America, which is directly related to rising incidence of type 2 diabetes. In addition, life lengthening of diabetic patients and ESRD patients receiving regular therapy are also important cause. According to data in the year of 1977, 40% of newly diagnosed ESRD patients in USA were caused by diabetes. Duo to enormous number and incessant increasing incidence of type 2 diabetic patients, type 2 diabetic nephropathy patients have already accounted for considerable proportion in the diabetic nephropathy patients who need dialysis. Recently in China the incidence of type 2 diabetes shows a tendency to escalate. It is expected that the number of diabetic patients will be up to 32 million in 2010.

α-Keto Acid is a product of amino acid deamination. Because it is nonnitrogenous and can accept amino to turn into the corresponding amino acid through transaminase in the body of patient with chronic renal failure, α-Keto Acid can reduce nitrogen supply, decrease urea production, stimulate protein synthesis, suppress protein decomposition, while offering adequate essential amino acids for body. Furthermore, α-Keto Acid and branched chain amino acids do not stimulate glucagon secretion and glucagon-induced cAMP secretion in liver, has no stimulating effect on hyperfiltration, thus contribute to delaying the progress of nephropathy.

It is extensively accepted that limited intake of diet protein to reduce kidney hyperfiltration and renal glomerulus internal pressure is effective in delaying the progress of nephropathy. But at present, debate exists in clinical research papers (such as MDRDS) to the role of low protein diet in delaying the progress of nephropathy. Adding compound α-Keto Acid tablet to low protein diet for patients can prevent essential amino acid deficiency and ameliorate severity of metabolism disorder, thus prevent malnutrition. Compared with standard diabetic diet, the aim of this study is to evaluate the efficacy and safety of compound α-Keto Acid tablet in combination with low protein diet in delaying the progress of nephropathy.

This is a multicentre, randomized, open-label, parallel group, diabetic diet controlled study. 240 patients who meet Inclusion/Exclusion criteria will be randomized into test groups or control groups at the ratio of 1:1. Test group will use low protein diet in combination with compound α-Keto Acid tablet, while control group will use routine diabetic diet, efficacy and safety of test group will be compared with those of control group after 1 year treatment. The study will be performed at 12 centres to ensure that at least 200 evaluable subjects are obtained.

STUDY OBJECTIVES:

• To compare the efficacy (ameliorating proteinuria and kidney injury) of compound α-Keto Acid tablet in combination with low protein diet with that of standard diabetic diet in delaying the progress of type 2 diabetic nephropathy.
• To compare the safety of compound α-Keto Acid tablet in combination with low protein diet with that of standard diabetic diet in delaying the progress of type 2 diabetic nephropathy.

Primary Endpoint: one year of treatment with Low Protein Diet plus α-Keto Acid or Diabetic Diet; Secondary Endpoint: Death, Dialysis or renal transplantation.

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200040
    • Shanghai Huashan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age < 75 years, regardless of sex;
• Final diagnosis of type 2 diabetes;
• Plasma glucose is under control (fasting plasma glucose<10mmol/L, glycosylated hemoglobin<8.0%) with oral glucose-lowering agents (confine to Repaglinide, α-glycosidase inhibitors, Gliquidone) and /or insulin;
• Even through RAS blocker (ACEI/ARB) is administrated at a fixed dose (the same as the starting dose, refer to appendix 4) for more than 6 weeks, blood pressure is still ≤ 160/90 mmHg;
• Patient is without dialysis and GFR is <60ml/min/1.73m2;
• Overt proteinuria is present two times within 2 weeks (urine albumin > 300mg/d in a 24-h collection)

Exclusion Criteria:

• Diabetic ketoacidosis within the last 6 months;
• Incapable of following study requirements to control diet;
• Glomerular filtration rate < 15 ml/min/1.73m2;
• Hypercalcemia or hyperkalemia (> normal upper limit);
• Other serious disease within the last 3 months;
• With obvious symptoms or signs of liver diseases, ALT or AST > two times normal upper limit;
• Severe edema or serous cavity effusion;
• Drug abuse
• Final diagnosis of malignant tumor;
• Receiving the long-term systematic steroid hormone treatment;
• Gestation already, prepares to be pregnant in the period of the trial, lactating women;
• Participate in other product clinical trial within 30 days prior to this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Ketosteril®; 1 tablet Ketosteril/5kgBW/d
Other: 2	Other: diabetic diet; Energy 30-35 Kcal/kg BW/d + protein 0.8 g/kg BW/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
changes in urine protein and GFR	one year

Secondary Outcome Measures

Outcome Measure	Time Frame
BMI(body mass index)	one year
Blood albumin and prealbumin	one year
Plasma High sensitivity C-reactive protein level	one year
plasma lipids	one year

Collaborators and Investigators

• Sponsor: Fresenius Kabi
• Investigators: Principal Investigator: Shantan Lin, Shanghai Huashan Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: August 13, 2006
• First Submitted That Met QC Criteria: August 13, 2006
• First Posted (Estimate): August 15, 2006

Study Record Updates

• Last Update Posted (Estimate): September 2, 2010
• Last Update Submitted That Met QC Criteria: September 1, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: nephropathy with type 2 diabetes
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: BFP503