The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combined Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension

This study has been completed.
Sponsor:
Information provided by:
Gulhane School of Medicine
ClinicalTrials.gov Identifier:
NCT00921570
First received: June 15, 2009
Last updated: June 16, 2009
Last verified: June 2009
  Purpose

Diabetic nephropathy (DN) is the most important complication of diabetes mellitus (DM) and the most common cause of end-stage renal disease (ESRD). Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/d or > 200 mcg/min) that is confirmed on at least 2 occasions 3 to 6 months apart, a relentless decline in the glomerular filtration rate (GFR), and elevated arterial blood pressure. In addition to the renal hemodynamic alterations, patients with overt diabetic nephropathy (dipstick-positive proteinuria and decreasing GFR) generally develop systemic hypertension. Hypertension is an adverse factor in all progressive renal diseases and seems especially so in diabetic nephropathy. The deleterious effects of hypertension are likely directed at the vasculature and microvasculature. Use of angiotensin converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers (ARBs), strict glycemic control and use of antilipidemic drugs may improve progression of DN.

TNF-like weak inducer of apoptosis (TWEAK, TNFSF12) is a member of the TNF superfamily of structurally related cytokines. The human TWEAK gene encodes a 249-amino acid type II transmembrane glycoprotein (30 kD). TWEAK may be expressed as a full-length, membrane-bound protein and as a 156-amino acid, 18-kD soluble protein, (sTWEAK) that results from proteolysis of TWEAK. TWEAK gene is expressed in many tissues, including brain, kidney, heart, arterial wall, monocytes and macrophages. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and chronic kidney disease (CKD).

Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD).

There is no data about the effects of Renin angiotensin system blockage (RAS), calcium channel blocker and combined drugs on TWEAK and PTX3 levels in diabetic proteinuric patients with hypertension. The aim of this study was to find out whether the beneficial effects of RAS blockage, calcium channel blocker and combined drugs in diabetic hypertensive proteinuric patients has any relation with the alteration of TWEAK and PTX3 levels. The investigators searched for the effects of angiotensin II (AII) receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and AII receptor blocker plus calcium channel blocker (Valsartan 160 mg + Amlodipine 10 mg) on the clinical and laboratory parameters of diabetic hypertensive proteinuric patients.


Condition Intervention Phase
Diabetes
Hypertension
Proteinuria
Drug: Amlodipine
Drug: Valsartan
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: The Effects of Renin Angiotensin System Blockage (RAS), Calcium Channel Blocker and Combine Drugs on TWEAK, PTX3 and FMD Levels in Diabetic Proteinuric Patients With Hypertension

Resource links provided by NLM:


Further study details as provided by Gulhane School of Medicine:

Primary Outcome Measures:
  • Flow mediated dilatation [ Time Frame: 12 weeks after ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • TWEAK, PTX-3, Systolic Blood Pressure and Diastolic Blood Pressure [ Time Frame: 12 weeks after ] [ Designated as safety issue: Yes ]

Enrollment: 105
Study Start Date: February 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amlodipine Drug: Amlodipine
calcium channel blocker (Amlodipine 10 mg) during 12 weeks
Experimental: Valsartan Drug: Valsartan
AII receptor blocker inhibitor (Valsartan 160 mg) during 12 weeks
Experimental: Valsartan+Amlodipine Drug: Amlodipine
calcium channel blocker (Amlodipine 10 mg) during 12 weeks
Drug: Valsartan
AII receptor blocker inhibitor (Valsartan 160 mg) during 12 weeks

Detailed Description:

The patients who were non-obese (BMI<30kg/m2), non dyslipidemic (total cholesterol <200mg/dl, Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of age and willing to participate to the study were screened. From the 375 patients with established type 2 diabetes mellitus+hypertension, 174 had proteinuria and/or hypertension (24 h protein excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90 mmHg, respectively). All cases were first referrals and at the time of the study all were off treatment. Patients with history of coronary artery disease, smokers and those taking statins or renin-angiotensin blockers were excluded because of the effect of these factors on endothelial dysfunction. Of 174 screened patients 107 met the study criteria and were included in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis was not known.

The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram, and with history of revascularization or myocardial infarction), C) elevated liver enzymes (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In order to evaluate the effect of RAS blockade on plasma TWEAK and PTX3 concentrations, patients with proteinuria were given an AII receptor blocker (Valsartan 160 mg), calcium channel blocker (Amlodipine 10 mg) and combine drug (Valsartan 160 mg + Amlodipine 10 mg) for 12 weeks. The effect of RAS blockade on insulin sensitivity and proteinuria was also investigated.

After the intervention period, blood samples were obtained for assay of plasma TWEAK and PTX3 concentrations, HbA1c , and insulin resistance scores (HOMA-IR).

Urine samples were also collected over a 24-hour period to determine the degree of proteinuria.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • CKD stage 1 patients
  • Older than 18 years of age
  • Type 2 Diabetic patients
  • Proteinuria
  • Hypertension

Exclusion Criteria:

  • History of coronary artery disease
  • Smokers
  • Taking statins or renin-angiotensin blockers
  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: NCT00921570

Locations
Turkey
GATA Nephrology
Ankara, Turkey, 06108
Sponsors and Collaborators
Gulhane School of Medicine
Investigators
Principal Investigator: Mahmut Ilker Yilmaz, MD GATA
  More Information

No publications provided by Gulhane School of Medicine

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00921570     History of Changes
Other Study ID Numbers: GATA VALAMEX study
Study First Received: June 15, 2009
Last Updated: June 16, 2009
Health Authority: Turkey: Ethics Committee

Keywords provided by Gulhane School of Medicine:
TWEAK
FMD
PTX3
Valsartan
Amlodipine
Renin Angiotensin System

Additional relevant MeSH terms:
Hypertension
Proteinuria
Vascular Diseases
Cardiovascular Diseases
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Valsartan
Amlodipine
Calcium Channel Blockers
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on September 16, 2014