Efficacy of Anti-Tubercular Vaccination in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00202410
• Other study ID #: NEU - BCG - 01
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: September 12, 2005
• Last updated: May 18, 2011
• Start date: November 2001
• Est. completion date: April 2008

Study information

• Verified date: May 2011
• Source: S. Andrea Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: April 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• Bacille of Calmette-Guerin
A single intracutaneous dose of 0.1 mL freeze-dried BCG (1 mg/mL; Berna Institute, Basel).

Other:
• placebo
subcutaneous administration of physiologic solution

Locations

Country	Name	City	State
Italy	Department of Neurology - University of Rome La Sapienza	Rome	Roma

Sponsors (3)

Lead Sponsor	Collaborator
S. Andrea Hospital	Istituto Superiore di Sanità, Italian Multiple Sclerosis Foundation

Country where clinical trial is conducted

Italy, 

References & Publications (7)

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. — View 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. — View Citation

Confavreux C, Suissa S, Saddier P, Bourdès 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. — View 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. — View 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-Guèrin (BCG) in multiple sclerosis. Neurology. 1999 Oct 22;53(7):1588-9. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of gad-enhancing lesions in T1		baseline and 6 months
Primary	number of lesions in T1 and new lesions in T2		baseline and 6 months
Secondary	volume of T2 lesions		0 and 6 months
Secondary	volume of T1 lesions (black holes)		0 and 6 months