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临床试验/NCT03664414
NCT03664414Unknown4 期

Pentoxifylline Effect on Renal Function, Oxidative Stress, Inflammation, and Fibrosis Markers, and Quality of Life in Patients With Diabetic Nephropathy

Maria Eugenia Galván Plata1 个研究点 分布在 1 个国家目标入组 196 人开始时间: 2018年3月1日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
4 期
发起方
入组人数
196
试验地点
1
主要终点
Change in the glomerular filtration rate

研究概览

简要总结

One of the purposes of the management of the patient with chronic kidney disease (CKD)is to slow the decline of renal function. The mechanisms by which the renal function declines involve inflammatory and fibrotic responses due in part by the effects of oxidative stress. Pentoxifylline (PTX)is a drug that stimulates adenosine receptors, and produces inhibition of phosphodiesterases, as well as being a dopaminergic modulator through D1 and D2 receptors. Its main effects are inhibition of the inflammatory state by decreasing serum levels of tumor necrosis factor alpha (TNF-ɒ) and monocyte chemo attractant protein 1 (MCP_1), which may slow down the decline of renal function. It also produces diminish of sympathetic activity, with the reduction of circulating levels of norepinephrine (NA), which may contribute to the reduction of glomerulosclerosis in diabetic patients. In the connective tissue increases the activity of the collagenases and decrease of collagen, fibronectin and glucosamine of the fibroblasts as well as inhibition of oxygen free radicals. Due to its antioxidant, anti-inflammatory and anti-fibrotic effects, PTX can result in an excellent therapeutic option for the prevention of CKD in DM2.

This work proposes the use of pentoxifylline as treatment CKD in DM2. Its application in patients with CKD will allow a therapeutic management with different targets, for its antioxidant, anti-inflammatory and antifibrotic effects that will be evaluated by means of fibrosis, inflammation and oxidative stress markers. The results will be of great importance in clinical practice, since they will justify the use of a new pharmacological tool, already known, with minimal adverse effects and low cost, accessible to all strata of the population since it is found as generic.

详细描述

Patients will be randomly selected from the outpatient family medicine clinics. Once included, patients will be randomly allocated (by a computer-generated randomization list) to a study or control group. Over a period of 2 years, patients of the study group will receive one PTX tablet (400 mg) orally three times a day (at dinner time), whereas controls will receive one cellulose identical tablet on the same schedule.

All patients will continue with their usual treatment prescribed by their family doctor. Monthly visits will be scheduled for clinical and biochemical evaluations. A blood sample will be taken at baseline and every six months up to 24 months, for measurement of complete blood count, urea, creatinine, glucose, albumin, lipids, electrolytes, liver function tests, serum total proteins, (will be measure by usual methods). In serum samples at 0, 6, 12, 18 and 24 months, high sensibility C reactive protein will be measured by nephelometry, Brain natriuretic peptide and Serum Cystatin C will be measured by ELISA. Glomerular filtration rate (GFR) will be calculated based in Cystatin C level Grubb's equations. Vitamin C will be measured by HPLC. A 24 h ambulatory blood pressure monitoring (24 h ABPM), M-mode and two-dimensional echocardiographic, and an analysis of body composition by bioelectrical impedance will be done at baseline 6, 12, 18 and 24 months. To investigate health-related quality of life the short-form 36 (SF-36) questionnaire will be applied. Treatment compliance will be recorded by counting tablets left in the container at the end of each monthly visit and by the Morinsky Green test.

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Double (Participant, Investigator)

盲法说明

Plaebo controlled

入排标准

年龄范围
30 Years 至 70 Years(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Type 2 diabetes mellitus
  • Microalbuminuria
  • Proteinuria.
  • Creatinine plasma clearance ˂ of 60 mL / min.
  • Exclusion criteria:
  • History of psychiatric disorders,
  • Immunosuppressants treatment
  • Herbalism Treatment
  • History of chronic alcoholism.
  • Type 1 diabetes mellitus.
  • Chronic obstructive pulmonary disease.
  • Pulmonary fibrosis
  • Heart failure
  • Liver cirrhosis.
  • Chronic hepatitis.

排除标准

  • 未提供

研究组 & 干预措施

Placebo group

Placebo Comparator

Placebo group will receive 1 tablet of cellulose pill to mimic pentoxifylline tablets three times a day with meals, during the following two years.

干预措施: pentoxifylline (Drug)

Pentoxifylline group

Active Comparator

Pentoxifillyne or experimental group will receive 400 mg of pentoxifylline three times a day with meals, during the following two years.

干预措施: pentoxifylline (Drug)

结局指标

主要结局

Change in the glomerular filtration rate

时间窗: The measurements will be done baseline and every six months up to 24 months.

It will be measure as to duplicate serum creatinine levels from baseline (mg/dL), or to pass from a stage of chronic kidney disease to he next stage (GFR mL/min)

次要结局

  • Change in health-related quality of life(The questionnaire will be applied baseline and every six months up to 24 months.)
  • Change in oxidative stress marker.(Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.)
  • Change in fibrosis markers.(Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.)
  • Change in inflammation markers.(Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.)

研究者

发起方
Maria Eugenia Galván Plata
申办方类型
Other Gov
责任方
Sponsor Investigator
主要研究者

Maria Eugenia Galván Plata

Coordinacion de Investigacion en Salud, México

Coordinación de Investigación en Salud, Mexico

研究点 (1)

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