Bacille Calmette-Guérin (BCG) Vaccine In Radiologically Isolated Syndrome (RIS)

NCT03888924 | Recruiting Phase 2

• 1 other identifier: BCG-RIS-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple sclerosis (MS) witnessed relevant therapeutic progress in the last decade. Following the extraordinary progress in the treatment of relapsing-remitting (RR) multiple sclerosis (MS), two major unmet needs remain to be addressed by translational research in this field: progressive MS and the "dream" of a world free of MS. As far as the latter is concerned, the investigators can hope to make the dream come true by understanding the etiology of the disease and hence design definitive cures. A more realistic and pragmatic perspective may be the prevention of the clinical onset of the disease, a research field that promises to become increasingly important as the integration of genetic data with endophenotypes, magnetic resonance imaging and other biomarkers ameliorates the ability to predict the development of the disease under clinical circumstance. Bacille Calmette-Guerin (BCG) vaccine has been tested with encouraging results in early MS and clinically isolated syndrome (CIS). The knowledge that disease-modifying therapies work best when used early in the demyelinating process raises the question about whether to try this approach - which is safe, cheap and handy - in individuals with radiologically isolated syndrome (RIS). Radiologically isolated syndrome is a new entity, diagnosed when the unanticipated magnetic resonance imaging (MRI) finding of brain spatial dissemination of focal white matter (WM) lesions highly suggestive of MS occurs in subjects without symptoms of MS, and with normal neurological examinations. Conversion to clinically isolated syndromes (CIS) were described in 84% of RIS individuals with spinal cord lesions over a median time of 1.6 years from the date of the first MRI. Whether or not to treat this condition remains currently a clinical conundrum. Bacille Calmette-Guérin (BCG) vaccine may have these characteristics since it resulted beneficial in early MS and first demyelinating episodes. Being safe, cheap and handy, the investigators propose to investigate its use to prevent progression of the demyelinating process in radiologically isolated syndrome. An approach such as BCG vaccine seems appropriate as a front-line immunomodulatory approach for RIS people. In a pilot study BCG vaccine was safe and effective in reducing disease activity at MRI, and the risk of developing persistent T1-hypointense lesions ('black holes' -BH- expression of tissue damage) in subjects with MS.

Conditions

Multiple Sclerosis

Keywords

BCG Vaccine; Radiologically Isolated Syndrome

Outcome Measures

Primary Outcomes (1)

• cumulative number of CUAL (new gadolinium T1-weighted lesions and non-enhancing new and newly enlarging T2-weighted lesions) on MRI scans over 1 year.

  To evaluate the cumulative number of new combined unique active lesions (CUAL; defined as new gadolinium T1-weighted lesions and non-enhancing new and newly enlarging T2-weighted lesions) on magnetic resonance imaging (MRI) scans over 1 year. Brain MRI will be acquired in all subjects at each centre using a magnet at 1.5T or 3T. * A sagittal survey image will be used to identify the anterior and posterior commissure (AC and PC). * A dual-echo, turbo spin-echo sequence (slice thickness: 3mm). * A high-resolution (3D, MPRAGE) T1- weighted image (slice thickness: 1mm). * A Magnetization Transfer (MT) sequence will be performed acquiring two 2-dimensional gradient-echo sequences, one without and one with MT saturation pulse (slice thickness: 3 mm). * A double inversion recovery (DIR) sequence * A T1-weighted scan, post-gadolinium injection, after 10-minute wait period. * A FLAIR sequence to be acquired between the DIR and the T1-weighted scans, after the gadolinium injection.

  12 months

Secondary Outcomes (1)

• Time to the first clinical event.

  36 months

Other Outcomes (5)

• number of cortical lesions

  6, 12, 24, 36 months

• Percentage of Brain Volume Changes (PBVC)

  6, 12, 24, 36 months

• Cortical and white matter Volume Changes

  6, 12, 24, 36 months

Study Arms (2)

BCG treated patients

EXPERIMENTAL

a single dose of Bacille Calmette-Guerin vaccine

Drug: Bacille Calmette-Guerin vaccine

Placebo treated patients

PLACEBO COMPARATOR

a single dose of placebo.

Drug: Placebo

Interventions

Bacille Calmette-Guerin vaccine DRUG

One dose (0.1 mL) contains 50 μg of the semi-dry mass of BCG bacilli, i.e. from 150,000 to 600,000 of live BCG bacilli (Bacillus Calmette-Guerin), the Brazilian Moreau substrain. One ampoule or vial with the powder contains: 0.5 mg (from 1.5 mln to 6 mln) of live BCG bacilli (Bacillus Calmette-Guerin), the Brazilian Moreau substrain. Powder: monosodium glutamate. Solvent: isotonic solution of sodium chloride.

Also known as: BCG 10 Anti-Tuberculosis Vaccine

BCG treated patients

Placebo DRUG

isotonic solution of sodium chloride (2mL vials).

Placebo treated patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female of any race and \> 18 years old.
• Diagnosis of RIS (4) within the last five years.
• Signed Informed Consent.

You may not qualify if:

• Pregnancy or lactation.
• Concomitant or previous use of immunosuppressive or immunomodulating treatment (except sporadic use of corticosteroids) within the last five years.
• Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation. Such conditions may include cardiovascular, pulmonary, hepatic, renal, severe systemic mycotic infections, metabolic diseases or malignancies, primary or secondary immunodeficiencies as determined by medical history, physical exam, laboratory tests, chest X-ray, electrocardiogram (ECG), and Mantoux reaction.
• Any medical or psychiatric condition that may affect the subjects ability to give informed consent, or to complete the study, or if the subject is considered by the treating neurologist to be, for any other reason, an unsuitable candidate for this study.
• Subjects with inability to successfully undergo MRI scans.
• Concomitant radiotherapy.
• Known hypersensitivity to any component of the vaccine.
• Past bone marrow stem cell transplantation and organ transplantation.
• Other vaccinations in the previous 4 weeks.

Sponsors & Collaborators

• S. Andrea Hospital: lead

Study Sites (1)

Center for Experimental Neurological Therapies (CENTERS), S. Andrea Hospital, Faculty of Medicine and Psychology, "Sapienza" University of Rome

Rome, 00139, Italy

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

BCG Vaccine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Giovanni Ristori

  S.Andrea Hospital, University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Ristori, MD

CONTACT

+390633776044; giovanni.ristori@uniroma1.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In order to guarantee a double blind design, participants, assessing neurologists and neuroradiologists will be masked to treatment allocation. A "two-physician-treating and assessing-model" will be used
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical director, PhD

Model Details: This is a phase II, double blind, randomized, controlled, multicenter study with two parallel groups of subjects.

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: March 25, 2019
• Study Start: June 17, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 29, 2024

Record last verified: 2024-11

Locations

IT (1)