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

Sponsor

Hospital Universitário Professor Edgard Santos (Other)

Overall Status

Completed

CT.gov ID

NCT01472263

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HTLV-1 Tropical Spastic Paraparesis Immune System Diseases Physical Disability Pentoxifylline	Drug: Pentoxifylline Drug: Placebo	Phase 3

Detailed Description

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Sep 1, 2012

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pentoxifylline	Drug: Pentoxifylline Pentoxifylline 400mg 3 times a day on a total dose o 1200mg, oral capsules Other Names: Trental
Placebo Comparator: Placebo	Drug: Placebo 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.

Arm

Intervention/Treatment

Experimental: Pentoxifylline

Drug: Pentoxifylline

Pentoxifylline 400mg 3 times a day on a total dose o 1200mg, oral capsules

Other Names:

Trental

Placebo Comparator: Placebo

Drug: Placebo

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.

Outcome Measures

Primary Outcome Measures

Functional neurological capacity [60 days]
Measure of functional neurological capacity with the Expanded Disability Status Scale (EDSS), OSAME Motor Disability Score and Ambulatorial index

Secondary Outcome Measures

Reduce in cytokines and chemokines [60 days]
Measure of reduce in inflammatory cytokines (TNF alpha, IFN gamma, IL10 and IL5) and chemokines (CXCL9 and CXCL10)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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