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

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

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.

Study Overview

• Status: Completed
• Conditions: Immune System Diseases; Physical Disability; Tropical Spastic Paraparesis; HTLV-1; Pentoxifylline
• Intervention / Treatment: Drug: Pentoxifylline; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40110
      • Hospital Universitario Professor Edgard Santos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hospital Universitário Professor Edgard Santos
• Investigators: Principal Investigator: Davi Costa, MD, Federal University of Bahia; Study Director: André Muniz Santos, MD, PhD, Federal University of Bahia; Study Chair: Edgar M Carvalho, MD, PhD, Federal University of Bahia

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: November 11, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Estimate): March 18, 2015
• Last Update Submitted That Met QC Criteria: March 17, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Immune System Diseases; Physical disability; pentoxifylline; HTLV-1; tropical spastic paraparesis
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Retroviridae Infections; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Central Nervous System Infections; Neuromuscular Manifestations; Spinal Cord Diseases; Muscle Hypertonia; Paresis; Myelitis; Deltaretrovirus Infections; HTLV-I Infections; Muscle Spasticity; Immune System Diseases; Paraparesis, Tropical Spastic; Paraparesis; Paraparesis, Spastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Pentoxifylline
• Other Study ID Numbers: INCT-DT