FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients

NCT ID: NCT01703234

Last Updated: 2012-10-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-01-31

Study Completion Date

2009-04-30

Brief Summary

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There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.

Detailed Description

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In recent years, diabetic nephropathy, which may lead to dialysis treatment, is the most prevalent underlying disease of people in developed countries. A wide range of studies have been carried out, from various points of view, to understand the progress of renal dysfunction in diabetic nephropathy. The endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) is elevated in patients with chronic kidney disease (CKD) and may have a role in the cardiovascular mortality and morbidity of these patients. In diabetic nephropathy, high ADMA levels were related to progression of diabetic nephropathy.

Fibroblast growth factor 23 (FGF-23) is a primary regulator of renal phosphate excretion. FGF23 is inversely associated with the GFR, a relationship underlying a fundamental mechanism for maintaining serum phosphate constancy during CKD progression. Such an adaptation may have deleterious trade-offs because, independently of serum phosphate, high FGF23 signals a high risk of death in ESRD patients. Some studies showed that there is a relationship between FGF-23 levels and proteinuria in CKD patients.

There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.

The study 'Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria' has been previously registered to ClinicalTrials.gov (Identifier:NCT00893425). The serum samples of the above study will be used in order to measure the FGF23 levels in this study. Therefore the eligibility criteria and the study design is similar to the previous study (Identifier:NCT00893425).

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 231 patients with established type 2 diabetes mellitus, 126 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 126 screened patients 78 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 FGF 23 concentrations, patients with proteinuria were given an ACE inhibitor (ramipril 10 mg/day) 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 FGF-23 concentrations, HbA1c , and insulin resistance scores (HOMA-IR).

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

Conditions

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Proteinuria Diabetic Nephropathy Chronic Kidney Disease

Keywords

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FGF-23 , ramipril, endothelial dysfunction

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Ramipril

Group Type EXPERIMENTAL

Ramipril

Intervention Type DRUG

ramipril 10 mg/day during 3 months

Interventions

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Ramipril

ramipril 10 mg/day during 3 months

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* History of coronary artery disease
* Smokers
* Taking statins or renin-angiotensin blockers
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Gulhane School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Mahmut Ilker Yilmaz

Assoc.Prof.

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Gulhane School of Medicine

Ankara, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

Other Identifiers

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GATARAMFGF232012

Identifier Type: -

Identifier Source: org_study_id