Clinical trial NCT05183516: Tdap and Biomarkers of Alzheimer's Disease
Official title: Evaluation of Tdap Vaccination and Plasma Biomarkers of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Alzheimer Disease, Late Onset
Keywords: Tdap
Alzheimer's
biomarkers
B. pertussis
immune risk profile
Lead sponsor: Mindful Diagnostics and Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Infectious Disease Society of America
First posted: 2022-01-10
Enrollment: 50
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single group assignment
Primary purpose: TREATMENT

Brief summary: Recently, the Tdap (tetanus toxoid, reduced diphtheria toxoid and acellular pertussis) vaccination was added to the list of immunizations associated with lower incidence of dementia. Plasma-based biomarkers for AD are a welcome alternative to expensive and invasive testing for Alzheimer's; these biomarkers include assessment of amyloid and tau and neurofilament light protein that assesses non-specific neurodegeneration. The investigators will test for these biomarkers, as well as some immune parameters, administer Tdap then repeat the blood tests in six months.

Detailed description: A growing number of studies have consistently shown reduced incident risk of dementia associated with a variety of vaccinations. Most recently, data probes of medical claims from two large and disparate databases showed that vaccination for tetanus, diphtheria and pertussis (Tdap) was associated with a 42% decrease in dementia. Adult vaccination coverage remains low for most routinely recommended vaccines, including Tdap. This study will screen and qualify participants who do not meet the recommended frequency interval for Tdap vaccination. Participants will have consented to a review of their medical history (including vaccination history), a neurocognitive test and a battery of blood tests. Included in the blood testing will be plasma-based testing for amyloid, tau and neurofilament light protein. The study will be considered a pilot study; it will be an open-label trial. All participants will receive a single dose of the Tdap vaccine. Nine months after vaccination, participants will repeat the pre-vaccine blood tests. Primary objective will be the assessment of change in the Alzheimer's disease (AD) biomarkers. Bordetella pertussis (B. pertussis), the bacterium that causes whopping cough, is one of the targets of the Tdap vaccine. B. pertussis is a hypothesized infectious trigger of Alzheimer's disease (AD). A secondary objective of the study will be determination of present and past infection by B. pertussis via IgG testing as well as PCR of nasal swab and how this may relate to the Alzheimer biomarker responses to Tdap vaccination.

Eligibility criteria: Inclusion Criteria:

* Immuno- competent
* Out of compliance for Tdap vaccine (none within 10 years).
* Ability of give informed consent.
* SAGE test 17 or greater

Exclusion Criteria:

* Immuno- compromised
* In compliance for Tdap vaccination (within 10 years).
* Known allergy to components of the Tdap vaccine.
* SAGE test \<17

Primary outcomes:
measure: Change in Plasma Amyloid
timeFrame: start of study and 6 months
measure: Change in Plasma Tau
timeFrame: start of study and 6 months
Secondary outcomes:
measure: Presence of B. pertussis
timeFrame: start of study and 6 months
measure: B. pertussis IgG
timeFrame: start of study
Other outcomes:
Locations:
city: Eau Claire
country: United States
facility: Mindful Diagnostics and Therapeutics
state: Wisconsin
Study officials:
affiliation: Mindful Diagnostics and Therapeutics
name: Coad T Dow, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scherrer JF, Salas J, Wiemken TL, Jacobs C, Morley JE, Hoft DF. Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination. J Gerontol A Biol Sci Med Sci. 2021 Jul 13;76(8):1436-1443. doi: 10.1093/gerona/glab115.
citation: Rubin K, Glazer S. The pertussis hypothesis: Bordetella pertussis colonization in the pathogenesis of Alzheimer's disease. Immunobiology. 2017 Feb;222(2):228-240. doi: 10.1016/j.imbio.2016.09.017. Epub 2016 Sep 28.
citation: Wiemken TL, Salas J, Morley JE, Hoft DF, Jacobs C, Scherrer JF. Comparison of rates of dementia among older adult recipients of two, one, or no vaccinations. J Am Geriatr Soc. 2022 Apr;70(4):1157-1168. doi: 10.1111/jgs.17606. Epub 2021 Dec 12.
citation: West T, Kirmess KM, Meyer MR, Holubasch MS, Knapik SS, Hu Y, Contois JH, Jackson EN, Harpstrite SE, Bateman RJ, Holtzman DM, Verghese PB, Fogelman I, Braunstein JB, Yarasheski KE. A blood-based diagnostic test incorporating plasma Abeta42/40 ratio, ApoE proteotype, and age accurately identifies brain amyloid status: findings from a multi cohort validity analysis. Mol Neurodegener. 2021 May 1;16(1):30. doi: 10.1186/s13024-021-00451-6.