Tdap and Biomarkers of Alzheimer's Disease

Alzheimer Disease, Late Onset Clinical Trial

Official title:

Evaluation of Tdap Vaccination and Plasma Biomarkers of Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05183516
• Other study ID #: Tdap PANDA
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: May 1, 2023
• Est. completion date: March 31, 2024

Study information

• Verified date: August 2022
• Source: Mindful Diagnostics and Therapeutics, LLC
• Contact: Coad T Dow, MD
• Phone: 715-577-5656
• Email: ctomdow[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: March 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Late Onset

Intervention

Biological:
• tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine
Tdap is a combination vaccine that protects against three potentially life-threatening bacterial diseases: tetanus, diphtheria, and pertussis (whooping cough).

Locations

Country	Name	City	State
United States	Mindful Diagnostics and Therapeutics	Eau Claire	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Mindful Diagnostics and Therapeutics, LLC	Infectious Disease Society of America

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Review. — View 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. — View 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 Aß42/40 ratio, ApoE prot — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Plasma Amyloid	Amyloid peptides 42/40 ratio	start of study and 6 months
Primary	Change in Plasma Tau	a brain-specific protein that may be expected to leak from brain interstitial fluid to the plasma compartment in Alzheimer's disease as well as its preclincial and prodromal stages.	start of study and 6 months
Secondary	Presence of B. pertussis	Nasal swab for the presence of B. pertussis	start of study and 6 months
Secondary	B. pertussis IgG	Blood test for history of B. pertussis	start of study