Clinical Trial Technology Development for the Validation of Surrogate Prognostic Markers in Patients With Diabetic Nephropathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Seoul National University Hospital
Sponsor:
Information provided by (Responsible Party):
Yon Su Kim, Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01673204
First received: August 21, 2012
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

Worldwide, the most common cause of chronic kidney disease (CKD) and end stage renal disease (ESRD) is diabetes. Unlike the past, in south korea, diabetes account for more than 40% of ESRD. According to WHO reports in 1998, 100 million people had type 2 diabetes in 1997, and there is expected to increase by 300 million people in 2025. In addition, the expected survival time of patients with diabetes increase compared to previous. In the future, ESRD due to type 2 diabetes is expected to have a significant impact on the health industry. Therefore, prevention of progression to CKD and ESRD in diabetic patients is important to aspect of national health and economic problems. How to stop the progression of diabetic nephropathy is part of modern medicine to be solved.

Strict glycemic control, blood pressure regulation, and use of renin-angiotensin system (RAS) blockers inhibit the development and progression of diabetic nephropathy. Microalbuminuria in diabetic patients has been recognized as a predictor of progression of diabetic nephropathy. Thus, the prevention of elevated urinary albumin excretion is an important therapeutic target for the prevention of renal and cardiovascular events.

In patients with diabetes and hypertension, the drugs that block the RAS are used to treat proteinuria, but still a large number of patients with proteinuria are uncontrolled. In addition, ACE inhibitors or ARB agents actually have a limited effect on reducing the risk of cardiovascular or renal outcome. Also, sulodexide or pentoxyphylline which is reducing proteinuria have some weak evidence in terms of efficacy and safety. Therefore, the introduction of new alternative drugs are required.

Already several study reported that calcitriol or paricalcitol in the renal injury model have renopreventive effect. In addition, in diabetic renal injury mice model reported that vitamin D receptor deficiency leads to glomerulosclerosis. Inhibition of the RAS with combination of paricalcitol and RAS inhibitors effectively prevent renal injury in diabetic nephropathy. Recently, Dick de Zeeuw et al reported that addition of paricalcitol to RAS inhibition safely lower residual albuminuria in patients with diabetic nephropathy. Recent studies reported that elevated concentrations of serum markers of the TNFα and Fas-pathways are strongly associated with decreased renal function in diabetic patients. However, the role of these markers in early progressive renal function decline are not clear. Therefore, the objective of this study is to identify the renoprotective effect as an new treatment of activated vitamin D (Calcitriol) indicating the TNF-α-related anti-inflammatory action and to seek the role as an important biomarker that the changes of TNFR in diabetic nephropathy can predict response to treatment.


Condition Intervention Phase
Diabetic Nephropathy
Drug: Calcitriol
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Screening

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • Changes in renal function with proteinuria [ Time Frame: 12 month after administration ] [ Designated as safety issue: No ]
    Comparison of in GFR level from baseline Comparison of proteinuria amount checked by random urine protein/creatinine ratio


Secondary Outcome Measures:
  • changes in sTNFR and TNF-related proteins [ Time Frame: 12 months after administration ] [ Designated as safety issue: No ]
    Comparison of serum TNFR1, TNFR2 levels from baseline


Estimated Enrollment: 276
Study Start Date: October 2012
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Calcitriol
Calcitriol
Drug: Calcitriol
dosage of 0.5mcg administered orally once daily for 12 month
Placebo Comparator: Placebo
Placebo
Drug: Placebo

  Eligibility

Ages Eligible for Study:   19 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients age 19-80 years
  • Clinically proven diabetic nephropathy
  • MDRD eGFR >= 30mL/min/1.73m2
  • Patients with residual urine protein/creatinine ratio >= 200mg/g
  • Adequate blood pressure control as treated systolic blood pressure <=140 or diastolic <=90 mmHg with RAS inhibitor for more than 3months
  • Serum intact PTH <500 mg/dL
  • Serum calcium <10.2 mg/dL
  • Patients who have not been treated vitamin D within the 3months prior to signing the informed consent form

Exclusion Criteria:

  • Patients age <19 years or > 80years
  • Patients with rapidly progressive glomerulonephritis
  • Patients requiring renal replacement therapy immediately
  • Hypercalcemia(Uncorrected serum calcium level >10.2 mg/dL) within recent 3month
  • Malignant hypertension
  • Heart failure (New York Heart Association functional class II to IV or LVEF <40%)
  • Severe chronic obstructive lung disease
  • Decompensated liver disease (ALT >3X upper normal limit)
  • Known allergy or hypersensitivity to vitamin D
  • Current treatment with steroids and/or immunosuppressive agents
  • Active primary malignancy requiring treatment or survival limits less than 2years
  • History of noncompliance to medical regimen
  • Inability to give an informed consent or to cooperate with researchers
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01673204

Contacts
Contact: Sumi Lee 82-2-2072-1724 promise131@hanmail.net

Locations
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Yonsu Kim, M.D., Ph.D    82-2-2072-2264    yonsukim@snu.ac.kr   
Contact: Dongki Kim, M.D., Ph.D    82-2-2072-2303    dkkim73@gmail.com   
Principal Investigator: Yonsu Kim, Ph.D.         
Sub-Investigator: Dongki Kim, M.D., Ph.D         
Sub-Investigator: Sumi Lee, M.D.         
Seoul National University Boramae Medical Center Not yet recruiting
Seoul, Korea, Republic of
Contact: Jungpyo Lee, M.D., Ph.D    82-2-870-2261    kjwa1@medimail.co.kr   
Sub-Investigator: Jungpyo Lee, M.D., Ph.D         
Sponsors and Collaborators
Seoul National University Hospital
Investigators
Study Chair: Yonsu Kim, M.D., Ph.D Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Yon Su Kim, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01673204     History of Changes
Other Study ID Numbers: SNUH-TNFR
Study First Received: August 21, 2012
Last Updated: February 12, 2014
Health Authority: Korea: Institutional Review Board

Keywords provided by Seoul National University Hospital:
surrogate marker,
circulating soluble TNF receptor,
diabetic nephropathy

Additional relevant MeSH terms:
Diabetic Nephropathies
Kidney Diseases
Urologic Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Calcitriol
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014