- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04449926
BCG and Plasma Amyloid in Non-Demented Adults
December 22, 2021 updated by: Mindful Diagnostics and Therapeutics, LLC
BCG vaccination, the most widely used vaccination in the world, is used to reduce risk of tuberculosis infection; it is used for other mycobacterial infections as well, benefiting leprosy and Buruli ulcer.
BCG has "heterologous" effects that aids in an array of non-mycobacterial and viral infections as well as bladder cancer.
It is the heterologous effect, sometimes called the "off-target" effect that may offer benefit in Alzheimer's disease.
Population studies and studies of adults receiving BCG show a lessened risk of Alzheimer's disease.
The study will see if BCG vaccination will alter a plasma test for amyloid, a biomarker for cerebral amyloid.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Alzheimer's disease (AD) is commonly regarded as Alzheimer's dementia.
It is now understood that changes in the brain that result in late-onset AD dementia start years or even decades prior to clinical dementia.
Biomarkers aid in diagnosing AD however, currently approved biomarkers have drawbacks as they are invasive and expensive.
The two most commonly used biomarkers are amyloid PET scan and spinal tap for amyloid and tau.
A new plasma amyloid test has received "Breakthrough Device Designation" from the US-FDA.
As an investigational tool, this blood test for amyloid peptides 42/40 levels accurately predicts brain amyloidosis in cognitively normal individuals.
In the past 100 years, four billion doses of BCG vaccination have been given for tuberculosis prevention.
A favorable effect with BCG for non-tuberculous mycobacteria is also recognized in cervical lymphadeniits, leprosy and Buruli's ulcer.
Recently, BCG has found favorable use in autoimmune diseases type 1 diabetes (T1D) and multiple sclerosis (MS); moreover, a protective role by BCG for Alzheimer's disease has been described.
Adult exposure to BCG lessened the risk of AD by four-fold.
This is an interventional pilot study to test 50 non-demented adults measuring their plasma amyloid 42/40 level prior to BCG prime/boost followed with the same plasma amyloid testing 9 months after vaccination.
Sub-clinical CMV infection is felt to drive immune senescence and increase the risk of AD; we will test for CMV antibodies and we will measure lymphocyte phenotype prior to BCG and at study end to look for an immune-modulating effect on this indicator of immunosenescence.
Study Type
Interventional
Enrollment (Actual)
49
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Wisconsin
-
Eau Claire, Wisconsin, United States, 54701-3016
- Mindful Diagnostics and Therapeutics
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- BCG naive
- Ability to read, understand and sign consent form
Exclusion Criteria:
- Known allergy to (components of) the BCG vaccine or serious adverse events to prior vaccine administration
- Known active or latent Mycobacterium tuberculosis or with another mycobacterial species. A history of - or a suspicion of M. tuberculosis infection.
- Fever (>38 C) within the past 24 hours.
- Suspicion of active viral or bacterial infection.
- Vaccination in the past 4 weeks or expected vaccination during the study period, independent of the type of vaccination.
- Severely immunocompromised subjects. This exclusion category comprises: a) subjects with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic subjects with less than 500 neutrophils/mm3; c) subjects with solid organ transplantation; d) subjects with bone marrow transplantation; e) subjects under chemotherapy; f) subjects with primary immunodeficiency; g) severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine therapies. i) treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months, or probable use of oral or intravenous steroids in the following four weeks.
- Active solid or non-solid malignancy or lymphoma within the prior two years.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BCG Vaccinated
Experimental: BCG Group FDA-approved BCG Tice strain, procured from Merck, will be used.
The vaccine will be reconstituted according to the package insert.
In brief, a vial containing ~1x10^8 CFU of lyophilized BCG will be reconstituted in 50 mL of saline.
A single dose will consist of 0.1 mL (~2x10^5 CFU) will be administered by slow intradermal injection using a 25 gauge/ 0.5 mm syringe in the deltoid area.
A follow up "booster" dose will be given one month after the initial dose.
|
Prime and boost vaccination
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Plasma Amyloid
Time Frame: 9 months
|
Level of Plasma Peptides 42/40 pre-BCG vaccination are compared with levels nine months post vaccination
|
9 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Immune Risk Profile
Time Frame: nine months
|
T-cell phenotype: CD4:CD8 ratios are measured pre-BCG vaccination and nine months post vaccination.
|
nine months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Coad T Dow, M.D., Mindful Diagnostics and Therapeutics
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Schindler SE, Bollinger JG, Ovod V, Mawuenyega KG, Li Y, Gordon BA, Holtzman DM, Morris JC, Benzinger TLS, Xiong C, Fagan AM, Bateman RJ. High-precision plasma beta-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019 Oct 22;93(17):e1647-e1659. doi: 10.1212/WNL.0000000000008081. Epub 2019 Aug 1.
- Gofrit ON, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL, Bercovier H. Bacillus Calmette-Guerin (BCG) therapy lowers the incidence of Alzheimer's disease in bladder cancer patients. PLoS One. 2019 Nov 7;14(11):e0224433. doi: 10.1371/journal.pone.0224433. eCollection 2019.
- Gofrit ON, Bercovier H, Klein BY, Cohen IR, Ben-Hur T, Greenblatt CL. Can immunization with Bacillus Calmette-Guerin (BCG) protect against Alzheimer's disease? Med Hypotheses. 2019 Feb;123:95-97. doi: 10.1016/j.mehy.2019.01.007. Epub 2019 Jan 11.
- Dow CT. Proposing BCG Vaccination for Mycobacterium avium ss. paratuberculosis (MAP) Associated Autoimmune Diseases. Microorganisms. 2020 Feb 5;8(2):212. doi: 10.3390/microorganisms8020212.
- Lurain NS, Hanson BA, Martinson J, Leurgans SE, Landay AL, Bennett DA, Schneider JA. Virological and immunological characteristics of human cytomegalovirus infection associated with Alzheimer disease. J Infect Dis. 2013 Aug 15;208(4):564-72. doi: 10.1093/infdis/jit210. Epub 2013 May 9.
- Westman G, Berglund D, Widen J, Ingelsson M, Korsgren O, Lannfelt L, Sehlin D, Lidehall AK, Eriksson BM. Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer's disease. PLoS One. 2014 May 7;9(5):e96779. doi: 10.1371/journal.pone.0096779. eCollection 2014.
- Luz Correa B, Ornaghi AP, Cerutti Muller G, Engroff P, Pestana Lopes R, Gomes da Silva Filho I, Bosch JA, Bonorino C, Bauer ME. The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults. Neuroimmunomodulation. 2014;21(4):206-12. doi: 10.1159/000356827. Epub 2014 Feb 6.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 9, 2020
Primary Completion (Actual)
December 4, 2021
Study Completion (Actual)
December 5, 2021
Study Registration Dates
First Submitted
June 24, 2020
First Submitted That Met QC Criteria
June 24, 2020
First Posted (Actual)
June 29, 2020
Study Record Updates
Last Update Posted (Actual)
December 23, 2021
Last Update Submitted That Met QC Criteria
December 22, 2021
Last Verified
December 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BCG-PANDA 01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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