Clinical Trial: Recombinant Human Interferon Beta-1a (Avonex) for the Treatment of Patients With HTLV-1-Associated Myelopathy (HAM)
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Combined Virological and Immunological Evaluation of Treatment of Patients With Early HTLV-1-Associated Myelopathy With Recombinant Human Interferon Beta-1a
Brief Summary:
HTLV stands for human T cell leukemia virus. HTLV-1 is a virus that attacks specific kinds of white blood cells called T cells. T cells are part of the natural defense system of the body. HTLV-1 has been associated with leukemia and lymphoma. In addition, approximately 1% of all patients infected with HTLV-1 develops a condition known as HTLV-1 associated myelopathy (HAM) / tropical spastic paraparesis (TSP).
Currently there is no clearly defined, effective treatment for patients with HAM/TSP. Steroids have been used as therapy but have only been able to provide temporary relief of symptoms. Human interferon is a small protein released from different kinds of cells in the body. Interferon has been known to have antiviral and immunological effects and has been used to treat hepatitis and multiple sclerosis. Interferon Beta is released from cells called fibroblasts. These cells play a role in the production of connective tissue.
The purpose of this study is to evaluate the possible role of recombinant interferon beta (Avonex) in treatment of HAM/TSP. The study is broken into three phases, a pre-treatment phase, a treatment phase, and a post-treatment phase. The total duration of the study will be 44 weeks.
Patients participating in this study will receive injections of Avonex 1 to 2 times a week. Throughout the study patients will regularly submit blood samples and undergo diagnostic tests such as MRI and measures of somatosensory evoked potentials.
Detailed Summary:
HTLV-1 has been linked to a chronic, slowly progressive neurologic condition termed HTLV-1 associated spastic paraparesis or tropical spastic paraparesis (HAM/TSP) which affects about 1% of the infected individuals. The disease is thought to be due to a T cell viral induced immunopathological process. A high frequency of HTLV-1 specific CD8 T cells are found in patients with HAM/TSP. The immune system of patients infected with HTLV-1 appears to be dysregulated, and increased spontaneous T cell proliferation can be demonstrated in vitro. This is in part due to continuous antigenic stimulation and due to transactivation by the HTLV-1 encoded Tax protein of host immunomodulatory genes such as CD80, CD86, IL-2 and its receptor. In addition, an increased viral load has been demonstrated in symptomatic individuals compared to asymptomatic HTLV-1 carriers. It is thought that the local immune response to the virus within the central nervous system plays a role in the pathogenesis of progressive spastic encephalomyeloneuropathy of HAM/TSP. Therefore, reduction of spontaneous T cell proliferation and viral replication, as well as decrease of the compromise of the blood brain barrier may ameliorate the immune-mediated component of the process which leads to inflammatory destruction of nervous tissue in HAM/TSP.
Currently there is no clearly defined, effective treatment of patients with HAM/TSP. Corticosteroids are the mainstay of therapy but provide mostly only transient symptomatic relief. Treatment with human interferon has been shown to improve acute and chronic hepatitis through its anti-viral and cytostatic effects. Further, patients with relapsing-remitting multiple sclerosis, a disease thought to be at least in part a T cell mediated, immunopathological process, exhibit a marked reduction of the frequency of new lesion formation while on this medication. This latter effect ma
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Current Primary Outcome:
Original Primary Outcome:
Current Secondary Outcome:
Original Secondary Outcome:
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: November 3, 1999
Date Started: September 1998
Date Completion: September 2004
Last Updated: March 3, 2008
Last Verified: September 2004
