Tdap and Biomarkers of Alzheimer's Disease

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Alzheimer Disease, Late Onset
• Intervention / Treatment: Biological: tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Coad T Dow, MD; Phone Number: 715-577-5656; Email: ctomdow@gmail.com
• Study Contact Backup: Name: Alie Halverson, CNA; Phone Number: 715-456-7336; Email: info@mindfuldt.com

Study Locations

• United States
  • Wisconsin
    • Eau Claire, Wisconsin, United States, 54701-3016
      • Mindful Diagnostics and Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tdap; Open label study, no placebo comparator	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).; Other Names: Tdap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma Amyloid	Amyloid peptides 42/40 ratio	start of study and 6 months
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of B. pertussis	Nasal swab for the presence of B. pertussis	start of study and 6 months
B. pertussis IgG	Blood test for history of B. pertussis	start of study

Collaborators and Investigators

• Sponsor: Mindful Diagnostics and Therapeutics, LLC
• Collaborators: Infectious Disease Society of America
• Investigators: Principal Investigator: Coad T Dow, MD, Mindful Diagnostics and Therapeutics

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: December 21, 2021
• First Posted (Actual): January 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: biomarkers; Tdap; Alzheimer's; B. pertussis; immune risk profile
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Disease Attributes; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Late Onset Disorders
• Other Study ID Numbers: Tdap PANDA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No participant data will be shared with other researchers.

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.: No