TCV -01-002: T-Cell Vaccination in the Treatment of Probable Multiple Sclerosis

T-Cell Vaccination in the Treatment of Probable Multiple Sclerosis

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: T cell vaccination

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.

• Study Type: Interventional
• Enrollment: 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba medical center
    • Contact: Anat Achiron, MD PhD; Phone Number: 972-3-5303932; Email: Achiron@post.tau.ac.il
    • Contact: Matilda Mandel, MD; Phone Number: 972-3-5304081
    • Sub-Investigator: Gad Lavie, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
The rate of progression to definite MS (second attack) during the study
Time to progression to definite MS (second attack)

Secondary Outcome Measures

Outcome Measure
Change in the count of new gadolinium (GD) enhancing lesions from two baseline (B) MRIs to the final (F) MRIs
Change in total volume of new GD enhancing lesions from two baseline MRIs (B) to the final MRIs (F)
The change in neurological disability as measured by the Expanded Disability Status Scale (EDSS)

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Anat Achiron, MD, PhD, Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, Israel; Principal Investigator: Mathilda Mandel, MD, Blood Bank, Sheba Medical Center, Tel-Hashomer, Israel

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Study Completion: December 1, 2006

Study Registration Dates

• First Submitted: September 26, 2005
• First Submitted That Met QC Criteria: September 27, 2005
• First Posted (Estimate): September 28, 2005

Study Record Updates

• Last Update Posted (Estimate): August 29, 2006
• Last Update Submitted That Met QC Criteria: August 27, 2006
• Last Verified: August 1, 2006

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; T-cell vaccination; Autoreactive T cells
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: SHEBA-01-2490-AA-CTIL