Multiple SclerosisPhase 2/3NCT00202410
Efficacy of Anti-Tubercular Vaccination in Multiple Sclerosis
A Phase 2/3 study testing Bacille of Calmette-Guerin in people with Multiple Sclerosis, run by S. Andrea Hospital at 1 site in Italy.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Bacille of Calmette-Guerin
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- Nov 2001to Apr 2008
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Neurology - University of Rome La Sapienza
Rome, Roma, 00100
About this study
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.
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.
Read more
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.
Read the 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.
- Conditions
- Multiple Sclerosis
- Being tested
- Bacille of Calmette-Guerin, placebo
- Keywords
- Multiple Sclerosis, Tuberculosis vaccine, Therapy
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bacille of Calmette-GuerinBiological
A single intracutaneous dose of 0.1 mL freeze-dried BCG (1 mg/mL; Berna Institute, Basel).
placeboOther
subcutaneous administration of physiologic solution
| Study group | Role | What they receive |
|---|---|---|
| physiologic solution | Placebo comparator | subcutaneous administration of physiologic solution Receives: Other: placebo |
| Bacille Calmette-Guèrin (BCG) Vaccine | Experimental | Anti-Tubercular Vaccination Receives: Biological: Bacille of Calmette-Guerin |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of gad-enhancing lesions in T1
Measured: baseline and 6 months
number of lesions in T1 and new lesions in T2
Measured: baseline and 6 months
Secondary outcomes (2)
volume of T2 lesions
Measured: 0 and 6 months
volume of T1 lesions (black holes)
Measured: 0 and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startNov 2001
- Primary completionSep 2007
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- S. Andrea Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Italian Multiple Sclerosis Foundation, Istituto Superiore di Sanità
- Investigators
- Marco Salvetti, Professor, Study director, S.Andrea Hospital, University of Rome "La Sapienza"Giovanni Ristori, MD, Principal investigator, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202410
- Sponsor's protocol ID
- NEU - BCG - 01
- Status last verified
- May 2011
- First submitted
- 12 Sep 2005
- Last updated
- 19 May 2011
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1212/wnl.53.7.1588.
PubMed 10534275Salvetti 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.
PubMed 7751856Confavreux 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.
PubMed 11172162Rook 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.
PubMed 11071529Buttinelli 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.
PubMed 11396455O'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.
PubMed 9549525Brex 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.
PubMed 10522870
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00202410
- Acronym / sponsor ID
- NEU - BCG - 01
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Tuberculosis vaccine, Therapy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- S. Andrea HospitalUniversity, hospital or other
- Collaborators
- Italian Multiple Sclerosis Foundation, Istituto Superiore di Sanità
- Study start
- Nov 2001
- Primary completion
- Sep 2007 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| physiologic solution | Placebo comparator | Other: placebosubcutaneous administration of physiologic solution |
| Bacille Calmette-Guèrin (BCG) Vaccine | Experimental | Biological: Bacille of Calmette-GuerinAnti-Tubercular Vaccination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bacille of Calmette-GuerinA single intracutaneous dose of 0.1 mL freeze-dried BCG (1 mg/mL; Berna Institute, Basel). | Biological | Bacille Calmette-Guèrin (BCG) Vaccine |
| placebosubcutaneous administration of physiologic solution | Other | physiologic solution |
Primary outcome
number of gad-enhancing lesions in T1
Time frame: baseline and 6 months
number of lesions in T1 and new lesions in T2
Time frame: baseline and 6 months
2 secondary outcomes
volume of T2 lesions
Time frame: 0 and 6 months
volume of T1 lesions (black holes)
Time frame: 0 and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2011.
- Background: PubMed 10534275Ristori 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.
- Background: PubMed 7751856Salvetti 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.
- Background: PubMed 11172162Confavreux 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.
- Background: PubMed 11071529Rook 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.
- Background: PubMed 11396455Buttinelli 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.
- Background: PubMed 9549525O'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.
- Background: PubMed 10522870Brex 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marco Salvetti, Professor study director
S.Andrea Hospital, University of Rome "La Sapienza"
Giovanni Ristori, MD principal investigator
University of Roma La Sapienza
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Bacille of Calmette-Guerin in people with Multiple Sclerosis, run by S. Andrea Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 May 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of gad-enhancing lesions in T1 (time frame: baseline and 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00202410, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2011.