Clinical trial NCT00001778: Evaluation of Patients With HAM/TSP
Official title: Immuno-Virological Evaluation of Human T Cell Leukemia Virus Type-1 Associated Myelopathy (HAM/TSP)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HTLV-I Infection
Tropical Spastic Paraparesis
Keywords: Immune Response
Sero-Indeterminant
Transmission
HTLV-1
HTLV-1 Associated Myelopathy
Natural History
HTLV-I
HAM/TSP
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 1999-11-04
Enrollment: 750
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals sero-positive for HTLV, individuals with indeterminate HTLV sero-status, and healthy volunteers are eligible to participate in this protocol. Some individuals sero-positive for HTLV may have associated diseases including but not limited to HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV associated inflammatory myositis.

Brief summary: Objective:

Human T-lymphotropic virus type-I-associated myelopathy / tropical spastic paraparesis (HAM/TSP) is a rare neurologic disorder that affects less than 5% of patients infected with the HTLV-I virus. The purpose of this protocol is to study the natural history of HAM/TSP by monitoring clinical progression of patients longitudinally. Additionally, we will attempt to define the virological and immunological changes of HAM/TSP.

Study Population:

Patients with HAM/TSP who fulfill World Health Organization diagnostic criteria are eligible to participate in this protocol. Asymptomatic seropositive individuals and individuals with indeterminate HTLV-1 serology are also eligible to participate.

Design and Outcome Measures:

A longitudinal assessment of clinical, virological and immunological progression in HAM/TSP will be accomplished through periodic testing and evaluation. Asymptomatic seropositive individuals, those with seroindeterminate HTLV-I serology and normal volunteers may serve as controls. Longitudinal standardized neurological examinations will be performed. Longitudinal samples of serum, plasma, and lymphocytes may be obtained from participants. Lumbar punctures may be performed on all participants. These samples will be used virological and immunological assays. A focus is on the relationships between the characteristics of viral infection, the immune response, and the genetic makeup.

Detailed description: Objective

Human T lymphotropic virus type 1 (HTLV-1) was first discovered in the search for retroviruses causing cancer in 1981. Shortly afterwards, HTLV-2 was also isolated. Although HTLV-1 and HTLV-2 share similar genome structure, routes of transmission, and replication pattern, they differ in epidemiology and disease associations. Human T-lymphotropic virus type-I-associated myelopathy / tropical spastic paraparesis (HAM/TSP) is a rare neurologic disorder that affects less than 5% of patients infected with the HTLV-I virus. Recently, a large body of literature supports other inflammatory manifestations, some neurological such as myositis, due to HTLV-1 infection. Studies of HLTV-2 clinical manifestations have largely been confounded by concomitant HIV-1 infection or IV drug abuse making the establishment of clear relationship with other manifestations such as neurological disease difficult. Most patients infected with HTLV remain asymptomatic throughout their lifetime. The purpose of this protocol is to study the natural history of HTLV infection by monitoring participants longitudinally. Additionally, we will attempt to define the virological and immunological changes of these viral infections. In addition, this protocol may be used to screen for other VIS protocols.

Study Population

Individuals sero-positive for HTLV, individuals with indeterminate HTLV sero-status, and healthy volunteers are eligible to participate in this protocol. Some individuals sero-positive for HTLV may have associated diseases including but not limited to HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV associated inflammatory disorders.

Design \& Outcome Measures

A longitudinal assessment of clinical, virological and immunological progression in HTLV related disease will be accomplished through periodic testing and evaluation. Asymptomatic seropositive individuals, those with sero-indeterminate HTLV serology and healthy volunteers may serve as controls. Longitudinal standardized neurological examinations will be performed. Longitudinal samples of serum, plasma, and lymphocytes may be obtained from participants. Lumbar punctures may be performed on all participants. These samples will be used for virological and immunological assays. A focus is on the relationships between the characteristics of viral infection, the immune response, and the genetic makeup.

Eligibility criteria: * INCLUSION CRITERIA:

Participants that meet one of the following criteria:

* Test positive for HTLV infection (positive HTLV-1 ELISA followed by a positive Western blot)
* Positive HTLV ELISA but a Western Blot that only partially fulfills the above criteria (seroindeterminate)
* Have a family member/significant other who is HTLV positive, and may have been exposed to the virus
* Healthy volunteer AND
* Willingness to participate in the protocol evaluations and procedures.

EXCLUSION CRITERIA:

* Unwillingness or inability to participate in the protocol evaluations and procedures.
* The presence of any medical, social, or psychiatric conditions that in the opinion of the investigator may affect the safety of the patients or compliance with the protocol.
* Patients/healthy volunteers under the age of 18 are excluded.

Primary outcomes:
measure: To characterize the baseline features of patients with HTLV infection with regards to clinical features, imaging studies, immunological markers, and viral studies.
timeFrame: each study visit
Secondary outcomes:
measure: Change in proviral load
timeFrame: each study visit
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
name: Steven Jacobson, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407-10. doi: 10.1016/s0140-6736(85)92734-5.
citation: Osame M, Matsumoto M, Usuku K, Izumo S, Ijichi N, Amitani H, Tara M, Igata A. Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells. Ann Neurol. 1987 Feb;21(2):117-22. doi: 10.1002/ana.410210203.
citation: Iwasaki Y. Pathology of chronic myelopathy associated with HTLV-I infection (HAM/TSP). J Neurol Sci. 1990 Apr;96(1):103-23. doi: 10.1016/0022-510x(90)90060-z.