Efficacy of Anti-Tubercular Vaccination in Multiple Sclerosis

Study Overview
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Brief Summary
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The frequency of auto-immune diseases (including multiple sclerosis) is increasing in industrialised countries. According to an hypothesis which is receiving a wide international credit, this may be due to the fact that the populations of these countries are increasingly less exposed to microbes further to the improvement of hygienic conditions and to the use of antibiotics. If exposure to microbes is lacking, also their regulatory function is missed with a consequent possible onset of auto-immune symptoms. For this reason, it is deemed that by exposing the immune system of a patient to an ancient microbe, being complex and important in man evolution, like the Tuberculosis Mycobacterium, it is possible to rebalance the immune system.

Detailed Description
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Vaccination with the Tuberculosis Mycobacterium has proved to be effective in the animal model of multiple sclerosis, experimental allergic encephalitis. In a study of phase I-II our group has demonstrated the safety of this therapy together with preliminary evidence. The study includes patients with an initial disease (diagnosis supported by paraclinical criteria): single clinical poly or mono-symptomatic attack in the 6 months preceding the study, MR picture compatible with MS. Study design 100 randomized patients (i.e. randomly assigned) to be included either in a group of 50 patients undergoing therapy or to a group of 50 patients receiving placebo. Patients are followed up with monthly contrast MRI for 6 months. At the end of the six months the disease activity in the group of treated patients is benchmarked with the disease activity of the group of patients receiving placebo. Safety is granted by the extremely wide diffusion of this kind of vaccination worldwide and by the previous study in patients affected by multiple sclerosis.

Official Title
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Phase 2-3 Use of Bacille Calmette-Guèrin (BCG) Vaccine in Patients With a First Clinical Demyelinating Episode: a Multicenter, Randomized, Single Blind Study.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: Bacille of Calmette-Guerin
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an initial disease (diagnosis supported by paraclinical criteria): single clinical poly or mono-symptomatic attack in the 6 months preceding the study, MR picture compatible with MS Exclusion Criteria: Therapy with corticosteroids in the last month Plasmapheresis, administration of gamma globulins in the last three months Serious heart, renal, hepatic or haematological dysfunction defined by laboratory exams Evidence of infections Evidence of tubercular disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: physiologic solution<br>subcutaneous administration of physiologic solution | Other: placebo<br>* subcutaneous administration of physiologic solution<br>|
| Experimental: Bacille Calmette-Guèrin (BCG) Vaccine<br>Anti-Tubercular Vaccination | Biological: Bacille of Calmette-Guerin<br>* A single intracutaneous dose of 0.1 mL freeze-dried BCG (1 mg/mL; Berna Institute, Basel).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of gad-enhancing lesions in T1 |  | baseline and 6 months | 
| number of lesions in T1 and new lesions in T2 |  | baseline and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| volume of T2 lesions |  | 0 and 6 months | 
| volume of T1 lesions (black holes) |  | 0 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Tuberculosis vaccine, Therapy