BCG and Plasma Amyloid in Non-Demented Adults

NCT04449926 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: BCG-PANDA 01
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease, Late Onset

Keywords

Alzheimer's disease; biomarker; BCG; plasma amyloid; peptides 42/40; heterologous effect; immune risk profile; CMV; HHV5; immunosenescence

Outcome Measures

Primary Outcomes (1)

• Change in Plasma Amyloid

  Level of Plasma Peptides 42/40 pre-BCG vaccination are compared with levels nine months post vaccination

  9 months

Secondary Outcomes (1)

• Change in Immune Risk Profile

  nine months

Study Arms (1)

BCG Vaccinated

EXPERIMENTAL

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.

Biological: Bacillus of Calmette and Guerin (BCG)

Interventions

Bacillus of Calmette and Guerin (BCG) BIOLOGICAL

Prime and boost vaccination

BCG Vaccinated

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BCG naive
• Ability to read, understand and sign consent form

You may not qualify if:

• 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.
• Active solid or non-solid malignancy or lymphoma within the prior two years.

Sponsors & Collaborators

• Mindful Diagnostics and Therapeutics, LLC: lead

Study Sites (1)

Mindful Diagnostics and Therapeutics

Eau Claire, Wisconsin, 54701-3016, United States

Location

Related Publications (7)

• 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.

  PMID: 31371569 BACKGROUND

• 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.

  PMID: 31697701 BACKGROUND

• 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.

  PMID: 30696606 BACKGROUND

• 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.

  PMID: 32033287 BACKGROUND

• 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.

  PMID: 23661800 BACKGROUND

• 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.

  PMID: 24804776 BACKGROUND

• 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.

  PMID: 24504177 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Coad T Dow, M.D.

  Mindful Diagnostics and Therapeutics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: June 29, 2020
• Study Start: November 9, 2020
• Primary Completion: December 4, 2021
• Study Completion: December 5, 2021
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)