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Trial registered on ANZCTR


Registration number
ACTRN12618001936213
Ethics application status
Approved
Date submitted
26/11/2018
Date registered
28/11/2018
Date last updated
11/03/2019
Date data sharing statement initially provided
28/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Bacille-Calmette-Guerin (BCG) vaccine for multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).
Scientific title
Safety study of Bacille-Calmette-Guerin (BCG) for multifocal motor neuropathy (MMN)
and multifocal acquired demyelinating sensory and motor neuropathy
(MADSAM).
Secondary ID [1] 296663 0
None
Universal Trial Number (UTN)
Trial acronym
BCGMMN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multifocal motor neuropathy 310500 0
Multifocal acquired demyelinating sensory and motor neuropathy (sometimes called asymmetric chronic inflammatory demyelinating polyradiculoneuropathy or Lewis Sumner syndrome) 310501 0
Condition category
Condition code
Neurological 309209 309209 0 0
Other neurological disorders
Inflammatory and Immune System 309291 309291 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Bacille Calmette Guerin (serum of institute of India) vaccine: single dose, intradermal injection into the upper arm, 0.1ml of reconstituted vaccine. This is given in addition to existing treatment such as intravenous immunoglobulin.
Intervention code [1] 312970 0
Treatment: Drugs
Comparator / control treatment
This is an uncontrolled study. This is a pre-post study design where post-intervention is compared to pre-intervention i.e. secondary outcomes will be measured for 3 months pre-intervention during a 'run-in' phase.
Control group
Active

Outcomes
Primary outcome [1] 308177 0
An excess of serious adverse events such as abscess, osteomyelitis or disseminated BCGosis. Participants will be provided with an information sheet of potential serious adverse events. Participants are encouraged to contact a researcher (via 24/7 contact details) if a potential serious adverse event occurs and clinical review organised if appropriate. Participants will also be questioned about adverse events at 3 monthly clinical reviews. The safety committee will review all potential adverse events during 3 monthly safety committee meetings.
Timepoint [1] 308177 0
Reported at anytime post-intervention or upon quarterly safety committee review
Primary outcome [2] 308178 0
Significant worsening of neuropathy as determined by 50% decline in grip strength (Martin Vigorimeter) in either hand compared to baseline or need for admission or rescue intravenous immunoglobulin
Timepoint [2] 308178 0
Reported at anytime post-intervention or upon quarterly safety committee review
Secondary outcome [1] 354176 0
Upper limb portion of Guy's neurological disability scale (GNDS)
Timepoint [1] 354176 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [2] 354177 0
Rasch-built overall disability scale for multifocal motor neuropathy (MMN-RODS)
Timepoint [2] 354177 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [3] 354178 0
Overall neuropathy limitations scale (ONLS)
Timepoint [3] 354178 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [4] 354179 0
Modified Rankin scale (mRS)
Timepoint [4] 354179 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [5] 354180 0
Medical outcome study 36-item short-form health status scale (SF-36)
Timepoint [5] 354180 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [6] 354181 0
9 hole peg test each hand
Timepoint [6] 354181 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [7] 354182 0
Grip strength measured by martin vigorimeter
Timepoint [7] 354182 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [8] 354183 0
Manual muscle score (modified Medical Research Council sum score)
Timepoint [8] 354183 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)
Secondary outcome [9] 354184 0
Current monthly intravenous immunoglobulin usage (as per last infusion) assessed with a study-specific outcomes form.
Timepoint [9] 354184 0
1. 3 months before intervention (pre-intervention 'run-in')
2. Within 2 weeks before intervention (pre-intervention 'run-in')
3. 3 and 6 months post intervention (post-intervention)

Eligibility
Key inclusion criteria
1. Fulfill EFNS criteria for definite or probable MMN or definite or probable atypical CIDP - MADSAM not benefitting from corticosteroids (no change or worsening)
2. Untreated or treatment with intravenous immunoglobulin and/or plasma exchange (MADSAM) acceptable
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Hyperergic on Mantoux reaction (induration greater than or equal to 5mm)
- Active or previously treated tuberculosis
- Current antituberculous therapy
- Active serious infection as determined by the treating clinician. If in doubt discuss with the safety committee. A patient can also be reconsidered at a later date.
- Previous serious adverse event to BCG
- Concurrent BCG use for other purpose (including intravesical use)
- Significant leukopaenia i.e. lymphocytes < 1.0, neutrophils < 1.0
- HIV infection (serology within the last 12 months)
- Known congenital or other immunodeficiency
- Recent immunosuppressive medication including oral corticosteroids in the previous 2 months or rituximab or cyclophosphamide in the previous 12 months, or other antiproliferative agent in the previous 6 months, or other immunosuppressive agent used in combination or separately that is deemed by the treating physician to contribute to a significant immunocompromised state
- Any other condition in the opinion of the local investigator that could increase patient risk by participation in the study
- Serious comorbidity with a life expectancy of < 2 years
- Pregnant (check pregnancy test in people capable of conception in the month before BCG injection)
- Inability to provide consent or undertake assessments

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
A sample size of 20 was chosen as this is a phase 1 pilot study and considered feasible based on specialist experience and estimate of prevalence and incidence of patients with MMN or MADSAM treated in Australian neurology clinics.

Primary outcomes will be presented descriptively. For secondary outcomes paired t-test or non-parametric paired rank test after review of data for parametric consistency, for individual comparisons of paired time points. Paired regression analysis with robust estimator of standard error for series analysis of time points. As the study is exploratory determination of analytical methods may be modified post-hoc.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2019
Actual
Date of last participant enrolment
Anticipated
7/04/2020
Actual
Date of last data collection
Anticipated
6/01/2021
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,TAS,WA,VIC
Recruitment hospital [1] 12471 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 12472 0
Westmead Hospital - Westmead
Recruitment hospital [3] 12473 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [4] 12474 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [5] 12475 0
Royal Perth Hospital - Perth
Recruitment hospital [6] 12476 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [7] 12477 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 12478 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 24772 0
2139 - Concord
Recruitment postcode(s) [2] 24773 0
2145 - Westmead
Recruitment postcode(s) [3] 24774 0
3050 - Parkville
Recruitment postcode(s) [4] 24775 0
3065 - Fitzroy
Recruitment postcode(s) [5] 24776 0
6000 - Perth
Recruitment postcode(s) [6] 24777 0
4029 - Herston
Recruitment postcode(s) [7] 24778 0
4102 - Woolloongabba
Recruitment postcode(s) [8] 24779 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 301241 0
Charities/Societies/Foundations
Name [1] 301241 0
Beeren foundation
Country [1] 301241 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Level 11, KGV Building
Missenden Road
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 300873 0
None
Name [1] 300873 0
Address [1] 300873 0
Country [1] 300873 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301980 0
Human Research Ethics Committee – CRGH Concord Repatriation General Hospital
Ethics committee address [1] 301980 0
Ethics committee country [1] 301980 0
Australia
Date submitted for ethics approval [1] 301980 0
25/10/2018
Approval date [1] 301980 0
18/01/2019
Ethics approval number [1] 301980 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88754 0
A/Prof Stephen W Reddel
Address 88754 0
Neurosciences Department
Concord Hospital
Hospital Road
Concord NSW 2137
Country 88754 0
Australia
Phone 88754 0
+61 2 97675000
Fax 88754 0
Email 88754 0
stephen.reddel@health.nsw.gov.au
Contact person for public queries
Name 88755 0
Alison Craig
Address 88755 0
Neurosciences Department
Concord Hospital
Hospital Road
Concord NSW 2137
Country 88755 0
Australia
Phone 88755 0
+61 2 97676819
Fax 88755 0
Email 88755 0
alison.craig@health.nsw.gov.au
Contact person for scientific queries
Name 88756 0
Stephen W Reddel
Address 88756 0
Neurosciences Department
Concord Hospital
Hospital Road
Concord NSW 2137
Country 88756 0
Australia
Phone 88756 0
+61 2 97675000
Fax 88756 0
Email 88756 0
stephen.reddel@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To preserve participant confidentiality.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.