Pentoxifylline in Lupus Nephritis (Pentoxifylline)
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|ClinicalTrials.gov Identifier: NCT03859570|
Recruitment Status : Not yet recruiting
First Posted : March 1, 2019
Last Update Posted : March 7, 2019
This is a randomized, double-blind, placebo-controlled clinical trial of pentoxifylline or placebo, administered in addition to standard of care therapy for patients with lupus nephritis at 4 sites to 40 subjects. Hence, this will be an "add-on" clinical trial, in which all patients will continue to receive their usual therapies for lupus nephritis throughout the 6 months of study duration.
This exploratory clinical trial is ultimately intended to inform the scientific basis for a subsequent, larger 12- month, randomized, double-blind, placebo-controlled clinical trial of Pentoxifylline (PTX) involving 100-150 patients with lupus nephritis and persistent proteinuria recruited from about 10-15 US medical centers. A trial of this size would be statistically adequately powered to answer numerous questions related to use of Pentoxifylline (PTX) in patients with lupus
|Condition or disease||Intervention/treatment||Phase|
|Lupus Nephritis||Drug: Pentoxifylline Drug: Placebos||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Masking Description:||Contracted biostatistician will be responsible for drug/placebo randomization. He will be able to conduct an early, interim data analysis following initial 30% enrollment, and will permit unblinding of subject data to the Data Safety Monitor (DSM) for reasons of safety assurance, as requested.|
|Official Title:||A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Pentoxifylline or Placebo in Addition to Standard of Care for Treatment of Proteinuria in Patients With Active Lupus Nephritis.|
|Estimated Study Start Date :||December 2019|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2022|
Pentoxifylline and standard of care therapy
Pentoxifylline (PTX) is a methylxanthine derivative that is a nonselective inhibitor of cyclic nucleotide phosphodiesterase (PDE). This enzyme, which has at least 5 subtypes, is responsible for inactivation of the important second messengers, Cyclic adenosine monophosphate (AMP) and cyclic guanosine monophosphate (GMP)
Other Name: Trental
Placebo Comparator: Placebo
Placebo and standard of care therapy
- Level of proteinuria [ Time Frame: 9 months ]Level of proteinuria measured as the protein/creatinine ratio on a morning first void specimen, recorded longitudinally at monthly intervals from baseline to 6 months, and from urine specimens provided monthly for 3 months following the 6 month study termination visit.
- Histopathologic subclass [ Time Frame: 6 months ]The effect of Pentoxifylline on proteinuria relative to disease duration and histopathologic subclass.We will stratify these subjects in to 3 groups: class II, class III/IV, and class V. Given the relatively low expected frequency of class II (about 20%) and class V (about 10%), and the small total number of subjects, we will likely only be able to observe trends in responses of proteinuria to Pentoxifylline treatment in the 3 groups, without observing significant differences between groups.
- Serum albumin [ Time Frame: 6 months ]Longitudinal changes in serum albumin over 6 months
- Glomerular Filtration Rate [ Time Frame: 6 months ]Longitudinal changes in glomerular filtration rate (GFR)
- Serologic markers [ Time Frame: 6 months ]Longitudinal changes in serologic markers including anti-DNA, complement component 3 (C3), and complement component 4(C4)
- SELENA-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Instrument Score [ Time Frame: 6 months ]Longitudinal changes in SELENA-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) Instrument Score. This tool is a cumulative and weighted index used to assess disease activity across 24 different disease descriptors in patients with Systemic Lupus Erythematosus.This assessment can be completed to objectively assess the patient's current state of disease. The descriptors with a weight of 8 are seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, cerebrovascular accident, and vasculitis. The descriptors with a weight of 4 are arthritis, myositis, urinary casts, hematuria, proteinuria, and pyuria. The descriptors with a weight of 2 are rash, alopecia, mucosal ulcers, pleurisy, pericarditis, low complement, and increased DNA binding. The descriptors with a weight of 1 are fever, thrombocytopenia, and leukopenia.
- Longitudinal changes in patient global activity score [ Time Frame: 6 months ]This score measures the disease activity from the patient's perspective. It is measured from 0 to 10 with 10 being the worst.
- Longitudinal changes in physician global activity score [ Time Frame: 6 months ]This score measures the disease activity from the physician's perspective.It is measured from 0 to 10 with 10 being the worst.
- Prednisone dose [ Time Frame: 6 months ]Longitudinal changes in prednisone dose (and total cumulative prednisone dose)
- Serum and urinary cytokine levels [ Time Frame: 6 months ]Correlation between serum and urinary cytokine levels (Tumor necrosis factor(TNF-alpha), Interleukin 1 (IL1), Interleukin 6 (IL6), Interleukin 2 (IL-2), Monocyte chemoattractant protein -1 (MCP-1), Transforming growth factor beta(TGF-beta), Interferon alpha (IFN-alpha), and Platelet-derived growth factor (PDGF) and changes in urinary protein excretion at baseline and at 1, 2, 3, and 6 months