Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001785
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Recombinant Human Interferon Beta-1a Avonex for the Treatment of Patients With HTLV-1-Associated Myelopathy HAM
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Combined Virological and Immunological Evaluation of Treatment of Patients With Early HTLV-1-Associated Myelopathy With Recombinant Human Interferon Beta-1a
Status:
COMPLETED
Status Verified Date:
2004-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 HAMTSP 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 HAMTSP 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
Currently there is no clearly defined effective treatment for patients with HAMTSP 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 HAMTSP 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 Description:
HTLV-1 has been linked to a chronic slowly progressive neurologic condition termed HTLV-1 associated spastic paraparesis or tropical spastic paraparesis HAMTSP 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 HAMTSP 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 HAMTSP 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 HAMTSP
Currently there is no clearly defined effective treatment of patients with HAMTSP 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 may in part be explained by an anti-inflammatory effect of interferon which allows repair of the blood brain barrier To evaluate possible role interferon beta in the treatment of HAMTSP we studied its effect on induction on regulatory factors and spontaneous in vitro proliferation of peripheral blood lymphocytes PBLs from HTLV-I infected individuals Recombinant interferon beta-1b inhibited spontaneous proliferation of PBLs from asymptomatic HTLV-1 carriers and patients with HAMTSP in a dose dependent manner and induced expression of interferon regulatory factor-2 which is associated with down regulation of proinflammatory cytokines such as interferon gamma These preliminary results indicate that treatment with interferon-b may ameliorate the immune dysregulation induced by HTLV-1 and may have therapeutic effect in the treatment of HAMTSP
Twelve patients will be treated with administration of recombinant human interferon-beta1a Assessment of efficacy will be based on reduction of spontaneous proliferation and proviral load As a secondary measure the clinical response of patients will be evaluated The study will entail an 8-week pretreatment period a 28-week treatment phase with escalation of the interferon-beta1a dose and a 12-week post-treatment phase In cases where dose escalation leads to intolerable side-effects patients will be continued at the highest tolerated dose of medication Spontaneous proliferation viral load and clinical parameters will be determined monthly
Currently there is no clearly defined effective treatment of patients with HAMTSP 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 may in part be explained by an anti-inflammatory effect of interferon which allows repair of the blood brain barrier To evaluate possible role interferon beta in the treatment of HAMTSP we studied its effect on induction on regulatory factors and spontaneous in vitro proliferation of peripheral blood lymphocytes PBLs from HTLV-I infected individuals Recombinant interferon beta-1b inhibited spontaneous proliferation of PBLs from asymptomatic HTLV-1 carriers and patients with HAMTSP in a dose dependent manner and induced expression of interferon regulatory factor-2 which is associated with down regulation of proinflammatory cytokines such as interferon gamma These preliminary results indicate that treatment with interferon-b may ameliorate the immune dysregulation induced by HTLV-1 and may have therapeutic effect in the treatment of HAMTSP
Twelve patients will be treated with administration of recombinant human interferon-beta1a Assessment of efficacy will be based on reduction of spontaneous proliferation and proviral load As a secondary measure the clinical response of patients will be evaluated The study will entail an 8-week pretreatment period a 28-week treatment phase with escalation of the interferon-beta1a dose and a 12-week post-treatment phase In cases where dose escalation leads to intolerable side-effects patients will be continued at the highest tolerated dose of medication Spontaneous proliferation viral load and clinical parameters will be determined monthly
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 98-N-0160 | None | None | None |