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Efficacy of Pentoxifylline on Primary Nephrotic Syndrome

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ClinicalTrials.gov Identifier: NCT00354731
Recruitment Status : Completed
First Posted : July 20, 2006
Last Update Posted : November 14, 2012
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
We aim to investigate (1) the effects of combined pentoxifylline and corticosteroids, compared to that of corticosteroids, on patients with primary nephrotic syndrome; and if possible (2) the effects of pentoxifylline monotherapy on patients with primary nephrotic syndrome not suitable for or intolerant of standard corticosteroid therapy.

Condition or disease Intervention/treatment Phase
Nephrotic Syndrome Drug: pentoxifylline Drug: Corticosteroid Phase 3

Detailed Description:

Pentoxifylline (PTX) is a phosphodiesterase inhibitor that is used clinically to treat patients with peripheral vascular disorders. In addition to its hemorheologic activity, PTX possesses potent anti-inflammatory and immunomodulatory properties. In vivo, PTX has shown its ability to attenuate nephrotic syndrome secondary to membranous glomerulonephritis and lupus nephritis, and to reduce subnephrotic proteinuria of early and advanced diabetic nephropathy. However, the anti-proteinuric effect of PTX has been traditionally attributed to down-regulation of tumor necrosis factor (TNF)-alpha. Whether or not other inflammatory mediators are also affected by PTX has never been studied. Our previous works have shown that PTX can inhibit cytokine or albumin-induced monocyte chemoattractant protein (MCP)-1 production in vitro, and attenuate proteinuria in association with suppression of renal MCP-1 messenger ribonucleic acid expression in experimental glomerulonephritis. More recently, we have found that PTX lowers proteinuria by modulating renal MCP-1 production in a subgroup of human glomerular diseases. In this study, we aim to investigate whether combination of PTX and corticosteroids results in additive reduction in proteinuria, and higher remission rates in patients with primary nephrotic syndrome. The secondary objective is to study whether PTX monotherapy can be effective in patients with primary nephrotic syndrome not suitable for or intolerant of corticosteroid therapy.

This study is a prospective, open-labeled, comparative study including primary nephrotic patients randomized into 2 groups. Group A receives oral PTX plus oral prednisolone, whereas group B receives oral prednisolone alone. The active treatment duration is 1 year for both subgroups. The dose for PTX will be 1,200 mg/day (for estimated glomerular filtration rate (GFR) ≧60 ml/min) or 800 mg/day (estimated GFR 59-30 ml/min) x 6 months, followed by stepwise reduction (800 mg/day x 6 M, 400 mg/day x 6 M and discontinued at 18 M). The dose for prednisolone will be 1 mg/kg/day for the initial 3 months, then the dose will be gradually tapered, thus by 6 months the dose will be 0.5 mg/kg/day, and at 12 months the dose will be reduced to around 5-10 mg/day, and discontinued at 18 M. For patients not considered suitable for (eg., active chronic hepatitis B virus or hepatitis C virus infection), or intolerance of (eg., concomitant diabetes mellitus, active peptic ulcer disease) standard corticosteroid therapy, PTX 1,200 mg/day will be administered to them for a total of 1 year. Serum and urine specimens will be collected before initiation of therapy (day 0), and at month 1, 3, 6, and 12 after the commencement of therapy. GFR will be calculated by Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formula. Urinary protein excretion will be quantitated by spot urine protein/creatinine ratio. All biochemical and immunological analyses will be performed by the Department of Laboratory Medicine, National Taiwan University Hospital. Serum and urine samples will be measured for inflammatory mediators and podocyte markers by using commercial ELISA kits.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Clinical Efficacy of Pentoxifylline on Patients With Primary Nephrotic Syndrome
Study Start Date : August 2006
Actual Primary Completion Date : January 2011
Actual Study Completion Date : April 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Active Comparator: corticosteroid
Oral prednisolone (1 mg/kg/day) x 3 M, followed by gradual tapering (0.5 mg/kg/day at 6 M, 0.25 mg/day at 12 M, and discontinued at 18 M
Drug: Corticosteroid
Oral prednisolone (1 mg/kg/day) x 3 M, followed by gradual tapering (0.5 mg/kg/day at 6 M, 0.25 mg/day at 12 M, and discontinued at 18 M
Other Name: Predonin

Experimental: Pentoxifylline + corticosteroid
Oral pentoxifylline 1,200 mg/day (for estimated GFR ≧60 ml/min) or 800 mg/day (estimated GFR 59-30 ml/min) x 6 months, followed by stepwise reduction (800 mg/day x 6 M, 400 mg/day x 6 M and discontinued at 18 M + oral prednisolone (1 mg/kg/day) x 3 M, followed by gradual tapering (0.5 mg/kg/day at 6 M, 0.25 mg/day at 12 M, and discontinued at 18 M
Drug: pentoxifylline
Oral pentoxifylline 1,200 mg/day (for estimated GFR ≧60 ml/min) or 800 mg/day (estimated GFR 59-30 ml/min) x 6 months, followed by stepwise reduction (800 mg/day x 6 M, 400 mg/day x 6 M and discontinued at 18 M
Other Name: Trental

Drug: Corticosteroid
Oral prednisolone (1 mg/kg/day) x 3 M, followed by gradual tapering (0.5 mg/kg/day at 6 M, 0.25 mg/day at 12 M, and discontinued at 18 M
Other Name: Predonin




Primary Outcome Measures :
  1. changes from baseline in urinary protein excretion [ Time Frame: 18 months ]

Secondary Outcome Measures :
  1. change from baseline in creatinine and estimated GFR [ Time Frame: 18 months ]

Other Outcome Measures:
  1. Urinary nephrin, TNF-alpha and MCP-1 [ Time Frame: 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • biopsied-proved primary glomerular diseases, and nephrotic syndrome

Exclusion Criteria:

  • History of allergy to pentoxifylline, Females are nursing or pregnant, Congestive heart failure (New York Heart Association functional class III or IV), Unstable angina, myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, within the past 6 months prior to signing the informed consent form, Cerebral hemorrhage within the past 6 months prior to signing the informed consent form, Retinal hemorrhage within the past 6 months prior to signing the informed consent form, Known or suspected secondary hypertension, Uncontrolled hypertension with systolic blood pressure > 200 mmHg and/or diastolic blood pressure > 110 mmHg, Liver cirrhosis, Biliary obstructive disorders, Active malignancy or infection, Uncontrolled diabetes mellitus, GFR ≦ 30 ml/min/1.73 m2

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00354731


Locations
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Taiwan
National Taiwan University Hospital
Taipei, Taiwan, 100
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
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Principal Investigator: Yung-Ming Chen, M.D. NTUH

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Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00354731     History of Changes
Other Study ID Numbers: 941103
First Posted: July 20, 2006    Key Record Dates
Last Update Posted: November 14, 2012
Last Verified: October 2012

Keywords provided by National Taiwan University Hospital:
nephrotic syndrome, pentoxifylline, corticosteroid

Additional relevant MeSH terms:
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Syndrome
Nephrotic Syndrome
Nephrosis
Disease
Pathologic Processes
Kidney Diseases
Urologic Diseases
Prednisolone
Pentoxifylline
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Radiation-Protective Agents
Protective Agents
Vasodilator Agents
Free Radical Scavengers
Antioxidants