Efficacy of Anti-Tubercular Vaccination in Multiple Sclerosis - Full Text View

Purpose

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.

Condition	Intervention	Phase
Multiple Sclerosis	Biological: Bacille of Calmette-Guerin Other: placebo	Phase 2 Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
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.

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis Tuberculosis

U.S. FDA Resources

Further study details as provided by S. Andrea Hospital:

Primary Outcome Measures:

number of gad-enhancing lesions in T1 [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
number of lesions in T1 and new lesions in T2 [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

volume of T2 lesions [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]
volume of T1 lesions (black holes) [ Time Frame: 0 and 6 months ] [ Designated as safety issue: No ]

Enrollment:	80
Study Start Date:	November 2001
Study Completion Date:	April 2008
Primary Completion Date:	September 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: physiologic solution subcutaneous administration of physiologic solution	Other: placebo subcutaneous administration of physiologic solution
Experimental: Bacille Calmette-Guèrin (BCG) Vaccine Anti-Tubercular Vaccination	Biological: Bacille of Calmette-Guerin A single intracutaneous dose of 0.1 mL freeze-dried BCG (1 mg/mL; Berna Institute, Basel).

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00202410

Locations

Italy
Department of Neurology - University of Rome La Sapienza
Rome, Roma, Italy, 00100

Sponsors and Collaborators

S. Andrea Hospital

Multiple Sclerosis Italian Foundation (FISM)

Istituto Superiore di Sanità (ISS)

Investigators

Study Director:	Marco Salvetti, Professor	S.Andrea Hospital, University of Rome "La Sapienza"
Principal Investigator:	Giovanni Ristori, MD	University of Roma La Sapienza

More Information

Publications:

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.

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.

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.

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. No abstract available.

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.

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.

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.

Responsible Party:	Marco Salvetti, University of Rome "Sapienza"
ClinicalTrials.gov Identifier:	NCT00202410 History of Changes
Other Study ID Numbers:	NEU - BCG - 01
Study First Received:	September 12, 2005
Last Updated:	May 18, 2011
Health Authority:	Italy: Ministry of Health

Keywords provided by S. Andrea Hospital:

Multiple Sclerosis
Tuberculosis vaccine
Therapy

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases

Immune System Diseases
Pathologic Processes
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013