search
Back to results

Low Protein Diet Supplemented With Ketoanalogs on Reducing Proteinuria and Maintaining Nutritional Status in Type 2 Diabetic Nephropathy

Primary Purpose

Type 2 Diabetic Nephropathy

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Compound α-Ketoacid Tablet
Sponsored by
Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetic Nephropathy focused on measuring Diabetic nephropathy, Podocyte, Low Protein Diet, Ketoanalogs

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • diagnosed with type 2 diabetes
  • age range is 18 - 80 years old
  • no gender restrictions
  • use oral hypoglycemic agents (limited to repaglinide, α-glucosidase inhibitor and chloroquine ketone) and/or insulin to control blood sugar
  • fasting blood sugar is not higher than 10mmol/l, glycated hemoglobin is not higher than 8.5%
  • using RAS system blockers (ACEI or ARB) for at least 4 weeks and blood pressure is no higher than 160/90mmHg. Once enrolled in the group, the dose should not be changed, unless there is contraindication
  • has not yet started dialysis, GFR based on simplified MDRD formula is between (15-60) ml/min/1.73m2
  • serum albumin is not less than 25g/l and appearing dominant proteinuria (urinary albumin excretion rate > 300mg/24h)
  • understanding and willing to participate in the trial and signed informed consent

Exclusion Criteria:

  • compliance is poor
  • GFR < 15ml/min/1.73m2
  • repeated hypercalcemia, hyperkalemia
  • ketoacidosis occurred in recent 6 months
  • chronic heart failure, above NYHA 3 grade
  • combined with other serious diseases in 3 months
  • obvious symptoms and signs of liver disease. Alanine or aspartate aminotransferase 2 times higher than normal
  • severe edema, or up to the level of nephrotic syndrome or that there is serous cavity effusion
  • urinary tract infections or other urinary tract diseases
  • drug abusers
  • diagnosed of malignancy
  • receiving long-term systemic steroid therapy
  • women pregnancy or Intended pregnancy and breastfeeding
  • took part in other clinical drug studies 30 days before the trial

Sites / Locations

  • Department of Nephrology,Shanghai Jiaotong University Affiliated First People's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ketosteril

Arm Description

Outcomes

Primary Outcome Measures

monitor podocyte loss by detecting nephrin, podocin, and synaptopodin mRNA in urine particulates with quantitative reverse transcriptase-PCR.
At baseline and every 3 months, a whole-stream early morning urine specimen will be collected for gene expression study.

Secondary Outcome Measures

Full Information

First Posted
February 18, 2011
Last Updated
September 6, 2011
Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Huashan Hospital, Shanghai East Hospital, Shanghai 6th People's Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT01300273
Brief Title
Low Protein Diet Supplemented With Ketoanalogs on Reducing Proteinuria and Maintaining Nutritional Status in Type 2 Diabetic Nephropathy
Official Title
Phase 4 Study of Mechanisms of Low Protein Diet Supplemented With Ketoanalogs on Reducing Proteinuria and Maintaining Nutritional Status in Type 2 Diabetic Nephropathy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2011
Overall Recruitment Status
Unknown status
Study Start Date
February 2011 (undefined)
Primary Completion Date
May 2012 (Anticipated)
Study Completion Date
July 2012 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Jiao Tong University School of Medicine
Collaborators
Huashan Hospital, Shanghai East Hospital, Shanghai 6th People's Hospital

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The investigators hypothesize that, LPD supplemented with ketoanalogs will reduce urine podocyte loss and lower the angiotensinogen level in the urine.
Detailed Description
Diabetic nephropathy is one of the most important causes of end stage renal disease in the world. Recently In a multicenter, randomized clinical trial performed in China, which aimed to evaluate the efficacy and safety of compound α-keto acid tablet in combination with low protein diet (LPD+KA) in delaying the progress of type 2 diabetic nephropathy(T2DN). In that study it was found that LPD+KA was associated with amelioration of proteinuria, better reduction in the loss of kidney function compared with LPD alone meanwhile nutrition status remained well in both group(Role of Ketoanalogs in diabetic nephropathy-China study, to be submitted for publication). However, in that study the mechanisms underlined these effects were not been elucidated This research proposal is a part of the continuation of that study. Restriction of Protein intake, strictly control blood pressure, particularly using renin-angiotensin system (RAS) blockade have been shown to ameliorate proteinuria and progression of CKD. Podocyte damage has been know to play critical role for proteinuria and renal function loss A recent study showed that the mRNA expression of podocyte markers in urinary sediment is increased in patients with T2DN, and this effect can be inhibited by ACE inhibitor and ARB, which indicates the important role of local renal RAS to involve in the damage. Urinary angiotensinogen level is a good marker of the situation of renal RAS. Consequently the investigators are proposing to study the effect of LPD+KA on podocyte as well as on local RAS in the kidney.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetic Nephropathy
Keywords
Diabetic nephropathy, Podocyte, Low Protein Diet, Ketoanalogs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketosteril
Arm Type
Experimental
Intervention Type
Dietary Supplement
Intervention Name(s)
Compound α-Ketoacid Tablet
Other Intervention Name(s)
Ketosteril, Ketoanalogs
Intervention Description
30 patients will be treated with a LPD containing 0.6g protein/kg BW per day and 120-125 kJ/kg BW per day and supplemented with keto-amino acids (Ketosteril®, Fresenius Kabi) at a dosage of 100 mg/kg BW per day.
Primary Outcome Measure Information:
Title
monitor podocyte loss by detecting nephrin, podocin, and synaptopodin mRNA in urine particulates with quantitative reverse transcriptase-PCR.
Description
At baseline and every 3 months, a whole-stream early morning urine specimen will be collected for gene expression study.
Time Frame
At baseline and every 3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: diagnosed with type 2 diabetes age range is 18 - 80 years old no gender restrictions use oral hypoglycemic agents (limited to repaglinide, α-glucosidase inhibitor and chloroquine ketone) and/or insulin to control blood sugar fasting blood sugar is not higher than 10mmol/l, glycated hemoglobin is not higher than 8.5% using RAS system blockers (ACEI or ARB) for at least 4 weeks and blood pressure is no higher than 160/90mmHg. Once enrolled in the group, the dose should not be changed, unless there is contraindication has not yet started dialysis, GFR based on simplified MDRD formula is between (15-60) ml/min/1.73m2 serum albumin is not less than 25g/l and appearing dominant proteinuria (urinary albumin excretion rate > 300mg/24h) understanding and willing to participate in the trial and signed informed consent Exclusion Criteria: compliance is poor GFR < 15ml/min/1.73m2 repeated hypercalcemia, hyperkalemia ketoacidosis occurred in recent 6 months chronic heart failure, above NYHA 3 grade combined with other serious diseases in 3 months obvious symptoms and signs of liver disease. Alanine or aspartate aminotransferase 2 times higher than normal severe edema, or up to the level of nephrotic syndrome or that there is serous cavity effusion urinary tract infections or other urinary tract diseases drug abusers diagnosed of malignancy receiving long-term systemic steroid therapy women pregnancy or Intended pregnancy and breastfeeding took part in other clinical drug studies 30 days before the trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weijie Yuan, Professor
Organizational Affiliation
Department of Nephrology, First People's Hospital, Shanghai Jiao Tong University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Nephrology,Shanghai Jiaotong University Affiliated First People's Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200080
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
9631839
Citation
Kasiske BL, Lakatua JD, Ma JZ, Louis TA. A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function. Am J Kidney Dis. 1998 Jun;31(6):954-61. doi: 10.1053/ajkd.1998.v31.pm9631839.
Results Reference
background
PubMed Identifier
16985512
Citation
Mahmood J, Khan F, Okada S, Kumagai N, Morioka T, Oite T. Local delivery of angiotensin receptor blocker into the kidney ameliorates progression of experimental glomerulonephritis. Kidney Int. 2006 Nov;70(9):1591-8. doi: 10.1038/sj.ki.5001872. Epub 2006 Sep 20.
Results Reference
background
PubMed Identifier
17596726
Citation
Wang G, Lai FM, Lai KB, Chow KM, Li KT, Szeto CC. Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy. Nephron Clin Pract. 2007;106(4):c169-79. doi: 10.1159/000104428. Epub 2007 Jun 26.
Results Reference
background
PubMed Identifier
18299464
Citation
Wang G, Lai FM, Lai KB, Chow KM, Kwan BC, Li PK, Szeto CC. Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. Eur J Endocrinol. 2008 Mar;158(3):317-22. doi: 10.1530/EJE-07-0708.
Results Reference
background
PubMed Identifier
17409316
Citation
Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukasawa H, Fujigaki Y, Kato A, Nakamura Y, Suzuki F, Hishida A. Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol. 2007 May;18(5):1558-65. doi: 10.1681/ASN.2006060554. Epub 2007 Apr 4.
Results Reference
background
PubMed Identifier
10662705
Citation
Adey D, Kumar R, McCarthy JT, Nair KS. Reduced synthesis of muscle proteins in chronic renal failure. Am J Physiol Endocrinol Metab. 2000 Feb;278(2):E219-25. doi: 10.1152/ajpendo.2000.278.2.E219.
Results Reference
background
PubMed Identifier
12920324
Citation
Sato N, Komatsu K, Kurumatani H. Late onset of diabetic nephropathy in spontaneously diabetic GK rats. Am J Nephrol. 2003 Sep-Oct;23(5):334-42. doi: 10.1159/000072915. Epub 2003 Aug 13.
Results Reference
background
PubMed Identifier
1870635
Citation
Verity MA. Infantile Pompe's disease, lipid storage, and partial carnitine deficiency. Muscle Nerve. 1991 May;14(5):435-40. doi: 10.1002/mus.880140509.
Results Reference
background

Learn more about this trial

Low Protein Diet Supplemented With Ketoanalogs on Reducing Proteinuria and Maintaining Nutritional Status in Type 2 Diabetic Nephropathy

We'll reach out to this number within 24 hrs