Clinical trial NCT00228228: TCV -01-002: T-Cell Vaccination in the Treatment of Probable Multiple Sclerosis
Official title: T-Cell Vaccination in the Treatment of Probable Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
T-cell vaccination
Autoreactive T cells
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2005-09-28
Enrollment: 80
Sex: ALL
Minimum age (years): 15
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In the present study, we, the investigators at Sheba Medical Center, intend to evaluate T cell vaccination (TCV) in patients with probable multiple sclerosis (MS) within up to 3 months after the first clinical attack. It is of the utmost importance to evaluate the treatment effects at the onset of disease, i.e. in patients with probable MS, in order to evaluate whether early treatment can prevent the second attack (conversion to definite MS). Moreover, at disease onset, the immunological process of epitope spreading associated with the exposure of the immune system to myelin antigens is still limited. With additional attacks, increased recognition of new self-determinants of encephalitogenic peptides presented to the immune system during the inflammatory process occurs, and enhances further disease activity. The aim of the early TCV treatment approach is to stop this process as early as possible, during the onset of the disease, thus preventing additional attacks and disease progression.

We will evaluate the effect of TCV on clinical, immunological and magnetic resonance imaging (MRI) parameters in patients with probable MS.

Detailed description: Inclusion criteria:

* Age: 15 - 50 years.
* Three months within the acute onset of neurological symptoms suggestive of the first attack of multiple sclerosis.
* Diagnosis of CPMS C3 (Poser criteria).
* Positive brain MRI according to Fazekas criteria.
* Negative pregnancy test and use of effective contraceptive for female patients who are sexually active.
* Signed written informed consent.

Exclusion criteria:

* Blood tests suggestive of other autoimmune diseases.
* Known allergic reactions to MRI contrast media.
* A clear regression of the neurological symptoms after the first attack that suggests a primary-progressive course.
* Corticosteroid treatment in the previous 4 weeks (28 days).
* Previous treatment with immunosuppressive medications such as cyclophosphamide, azathioprine, methotrexate, mitoxantrone or cyclosporine.
* Previous treatment with interferon beta 1a or 1b, copolymer-1, IVIg, plasmapheresis.

Eligibility criteria: Inclusion Criteria:

* Ages 15-50
* Three months within the acute onset of neurological symptoms suggestive of multiple sclerosis
* Diagnosis of clinically probable MS (CPMS) C3: 1 attack with at least 1 clinical manifestation in addition to positive brain MRI as defined in the protocol, signifying paraclinical evidence (Poser criteria 1983).
* Positive Brain MRI: at least 4 focal lesions involving the white matter of 3 lesions if one is periventricular \> 3mm diameter, each
* Negative pregnancy test and use of effective contraceptives for female patients who are sexually active.
* Signed written informed consent.

Exclusion Criteria:

* Blood tests suggestive of other autoimmune diseases
* Known allergic reaction to MRI contrast media.
* A clear regression of the neurological symptoms after the first attack that excludes a primary progressive course.
* Corticosteroid treatment in the previous 4 weeks.
* Previous treatment with immunosuppressive medications such as cyclophosphamide, azathioprine, methotrexate, mitoxantrone, or cyclosporine.
* Previous treatment with interferon beta 1a or 1b copolymer-1 IVIg, plasmapheresis.

Primary outcomes:
measure: The rate of progression to definite MS (second attack) during the study
measure: Time to progression to definite MS (second attack)
Secondary outcomes:
measure: Change in the count of new gadolinium (GD) enhancing lesions from two baseline (B) MRIs to the final (F) MRIs
measure: Change in total volume of new GD enhancing lesions from two baseline MRIs (B) to the final MRIs (F)
measure: The change in neurological disability as measured by the Expanded Disability Status Scale (EDSS)
Other outcomes:
Locations:
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel
name: Anat Achiron, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Blood Bank, Sheba Medical Center, Tel-Hashomer, Israel
name: Mathilda Mandel, MD
role: PRINCIPAL_INVESTIGATOR
References: