T Cell Vaccination in Patients With Progressive Multiple Sclerosis
|Multiple Sclerosis||Biological: multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides) Biological: T cell vaccination||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Autologous T Cell Vaccination With Line Specific for 9 Myelin Peptides in Patients With Progressive / Relapsing Multiple Sclerosis|
- EDSS changes [ Time Frame: one year ]Follow up in changes in the EDSS score
- Relapse rate of MS [ Time Frame: one year follow up ]recording of the relapses of MS during the year of the study and the prior to the study
- PASAT test [ Time Frame: one year ]recording of the performance in the PASAT test during the one year of the study
- Nine hole PEG test [ Time Frame: one year ]recording of the performance in the Nine hole PEG test test during the one year of the study
- timed ten meter walking [ Time Frame: one year ]recording of the performance in the timed ten meter walking test during the one year of the study
- Quantitative MRI evaluation [ Time Frame: one year ]the burden of T2 lesions load, of the hypo-intense T1 lesions, of the Gadolinium enhancing lesions and of the brain atrophy will be evaluated at the end of the study and compared to the baseline values
|Study Start Date:||May 2002|
|Study Completion Date:||March 2009|
|Primary Completion Date:||September 2008 (Final data collection date for primary outcome measure)|
Active Comparator: TCV
multiple T cell vaccinations against nine myelin peptides at days 1, 30, 90, 180
Biological: T cell vaccination
Multiple injections of autologous T cell lines reactive to 9 myelin peptides.
Sham Comparator: Placebo
saline injections subcutaneously at the same 4 time points with active treatment
Biological: multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides)
multiple (4 autologous subcutaneous T cell vaccinations with T cell lines reactive to nine myelin peptides at days 1, 30,90,180
Other Name: multiple subcutenous injections of saline at days 1, 30,90,180.
This trial is a phase I/II double-blind controlled clinical trial designed to evaluate the safety and clinical efficacy of multiple autologous T-cell vaccinations (on days 1, 30, 90 and 180) in progressive MS patients which showed severe progression/deterioration in the functional status (at least, one degree in the EDSS scale) during the last year, or at least one severe relapse. The patients will be from our MS clinic and will be randomized (by computer) into two groups according to: age, disease duration, disease severity and progression rate. One group (2/3 of the patients) will receive the active treatment, i.e. TCV, and the other group (1/3 of the patients) will receive sham treatment (injection of sterile normal saline). The treating nurse, the treating physician, the examining neurologist (the one who will perform the neurological evaluation) and the patient will be blinded for the treatment.
OBJECTIVES AND SIGNIFICANCE OF THE TRIAL
A. To develop a new cell therapeutic modality for treating MS patients using attenuated autologous anti-MBP, anti-PLP and anti-MOG autoreactive T-cells as vaccines. The immune response induced by this vaccination will be directed specifically against the T-cells attacking the patient's nerve system (specifically the myelin sheath).
B. To study and characterize these autoreactive T-cells in MS patients. The number and function of such cells in the course of the relapse of the disease, as well as during the periods of remissions, will be studied.
C. To study the clinical efficacy of T-cell vaccination with attenuated anti-MBP and anti-MOG autologous T-cells on MS. The parameters to be examined will include: change in the disability status (by the EDSS disability scale, as well as by ambulation index and several other functional tests), the change in the relapse rate and in the timed 10-meters walking test, the PASAT test and the 9-hole peg test. MRI parameters will represent additional endpoints and will include: the changes in the total burden of the disease and in the quantity of irreversible damage (cortical atrophy and axonal loss). In addition, the effects of this treatment on the immune responses (i.e. number and proportion of activated lymphocytes, number and proportion of anti-myelin reactive lymphocytes in the peripheral blood and IgG antibody levels in the cerebrospinal fluid) will be evaluated in the treated MS patients.
The significance and importance of the study are outlined as follows:
- It offers a new approach for the treatment of MS.
- This approach has the advantage of being devoid of toxic or general immunosuppressive effects.
- The study will pave the way for further studies that will improve our understanding of the mechanisms of the host immune response in MS and of the involvement of the MBP, PLP and MOG myelin proteins in the initiation of the auto-reactive immune response and of clinical MS.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01448252
|Dept of Neurology,Hadassah ein-Kerem|
|Jerusalem, Israel, 91120|
|Principal Investigator:||Dimitrios Karussis, Prof.||Hadassah Medical Organizatin|
|Study Director:||Rivka Abulafia-Lapid, PhD||Hadassah Medical Organization|