Clinical trial NCT00202410: Efficacy of Anti-Tubercular Vaccination in Multiple Sclerosis
Official title: Phase 2-3 Use of Bacille Calmette-Guèrin (BCG) Vaccine in Patients With a First Clinical Demyelinating Episode: a Multicenter, Randomized, Single Blind Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Tuberculosis vaccine
Therapy
Lead sponsor: S. Andrea Hospital
Sponsor class: OTHER
Collaborators: name: Italian Multiple Sclerosis Foundation
name: Istituto Superiore di Sanità
First posted: 2005-09-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: number of gad-enhancing lesions in T1
timeFrame: baseline and 6 months
measure: number of lesions in T1 and new lesions in T2
timeFrame: baseline and 6 months
Secondary outcomes:
measure: volume of T2 lesions
timeFrame: 0 and 6 months
measure: volume of T1 lesions (black holes)
timeFrame: 0 and 6 months
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Neurology - University of Rome La Sapienza
state: Roma
Study officials:
affiliation: S.Andrea Hospital, University of Rome "La Sapienza"
name: Marco Salvetti, Professor
role: STUDY_DIRECTOR
affiliation: University of Roma La Sapienza
name: Giovanni Ristori, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ristori G, Buzzi MG, Sabatini U, Giugni E, Bastianello S, Viselli F, Buttinelli C, Ruggieri S, Colonnese C, Pozzilli C, Salvetti M. Use of Bacille Calmette-Guerin (BCG) in multiple sclerosis. Neurology. 1999 Oct 22;53(7):1588-9. doi: 10.1212/wnl.53.7.1588.
citation: Salvetti M, Pisani A, Bastianello S, Millefiorini E, Buttinelli C, Pozzilli C. Clinical and MRI assessment of disease activity in patients with multiple sclerosis after influenza vaccination. J Neurol. 1995 Feb;242(3):143-6. doi: 10.1007/BF00936886.
citation: Confavreux C, Suissa S, Saddier P, Bourdes V, Vukusic S; Vaccines in Multiple Sclerosis Study Group. Vaccinations and the risk of relapse in multiple sclerosis. Vaccines in Multiple Sclerosis Study Group. N Engl J Med. 2001 Feb 1;344(5):319-26. doi: 10.1056/NEJM200102013440501.
citation: Rook GA, Ristori G, Salvetti M, Giovannoni G, Thompson EJ, Stanford JL. Bacterial vaccines for the treatment of multiple sclerosis and other autoimmune disorders. Immunol Today. 2000 Oct;21(10):503-8. doi: 10.1016/s0167-5699(00)01700-x. No abstract available.
citation: Buttinelli C, Salvetti M, Ristori G. Vaccinations and multiple sclerosis. N Engl J Med. 2001 Jun 7;344(23):1794; author reply 1795-6. No abstract available.
citation: O'Riordan JI, Thompson AJ, Kingsley DP, MacManus DG, Kendall BE, Rudge P, McDonald WI, Miller DH. The prognostic value of brain MRI in clinically isolated syndromes of the CNS. A 10-year follow-up. Brain. 1998 Mar;121 ( Pt 3):495-503. doi: 10.1093/brain/121.3.495.
citation: Brex PA, O'Riordan JI, Miszkiel KA, Moseley IF, Thompson AJ, Plant GT, Miller DH. Multisequence MRI in clinically isolated syndromes and the early development of MS. Neurology. 1999 Oct 12;53(6):1184-90. doi: 10.1212/wnl.53.6.1184.