Use of Pentoxifylline in Human T-lymphotropic Virus Type-1 (HTLV-1) Diseases

Study Overview
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Brief Summary
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In this study the investigators are going to evaluate the efficacy pentoxifyline in HTLV-1 patients with neurological diseases: HAM/TSP or neurogenic bladder. In some laboratory experiments the investigators observed that this drug had the capacity to reduce the immune response in HTLV-1 infected cells. Since the exacerbated immune response is know to cause neurological disease in patients with HTLV-1 the investigators hope that pentoxifyline can alleviate symptoms and delay the progress of HAM/TSP in patients.

Detailed Description
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The human T-lymphotropic virus type 1 (HTLV-1) infects 20 million individuals worldwide and is the causative agent of HTLV associated myelopathy/ tropical spastic paraparesis (HAM/TSP). Although only 5% of HTLV-infected individuals will develop HAM/TSP, the investigatorts have observed that about 30% have neurological complaints and/or neurogenic bladder associated with HTLV-1. The immunopathogenesis of those diseases is related to the exaggerated immune response with high production of cytokines and induced neurological injury. So far there is not any effective drug against HTLV-1 and modulation of the immune response can help to alleviate the clinical manifestations of those patients and prevent the progression of symptoms. The preliminary data show that pentoxifylline has ability to decrease production of TNF-α and IFN-γ in patients with HTLV-1 infection and patients with HAM/TSP. The proposal entitled Evaluation of the efficacy of pentoxifylline in attenuating the neurological disease associated with HTLV-1 and negatively modulate the immune pathological response extends the previous studies in order to determine the ability of pentoxifylline in modulate the immune response and modify the course of the clinical manifestations in patients infected with HTLV-1. The influence on the immune response in the expression of disease will be determined in a therapeutic trial with two groups of patients: 1) patients with neurogenic bladder associated with HTLV-1, 2) patients with HAM/TSP. Primary end point is clinical and neurological exam and secondary end point are measure of proinflammatory cytokines (TNF-α, IFN-γ, IL-1 and IL-6) and chemokines that attract T cells to sites of inflammation (CXCL9 and CXCL10).

Official Title
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Effectiveness of Pentoxifylline in Attenuating Neurological Disease Associated With HTLV-1 and Negative Modulator of Pathological Immune Response.

Conditions
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HTLV-1, Tropical Spastic Paraparesis, Immune System Diseases, Physical Disability, Pentoxifylline

Intervention / Treatment
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* Drug: Pentoxifylline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 80 years; Confirmed HTLV-1 infection with Western Blot analysis; HAM/TSP diagnosed patients according to the WHO Patients with HTLV-1 and neurogenic bladder diagnosed by clinical and urodynamic study Disease duration < 5 years Exclusion Criteria: Neurological diseases with functional limitations. Co-infection with Hepatitis B or C, Syphilis, Chagas Disease or HIV Use of immunossupressive drugs Immune disease Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pentoxifylline<br> | Drug: Pentoxifylline<br>* Pentoxifylline 400mg 3 times a day on a total dose o 1200mg, oral capsules<br>* Other names: Trental;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo capsules 3 times a day. The capsules have the same shape, color and form as the treatment group, and are identified by envelope numbers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional neurological capacity | Measure of functional neurological capacity with the Expanded Disability Status Scale (EDSS), OSAME Motor Disability Score and Ambulatorial index | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduce in cytokines and chemokines | Measure of reduce in inflammatory cytokines (TNF alpha, IFN gamma, IL10 and IL5) and chemokines (CXCL9 and CXCL10) | 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HTLV-1, tropical spastic paraparesis, Immune System Diseases, Physical disability, pentoxifylline