Clinical trial NCT03104075: Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines
Official title: Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumonia
Aging
Keywords: Genomics
Epigenomics
Pneumococcal vaccine
Elderly
Lead sponsor: The Jackson Laboratory
Sponsor class: OTHER
Collaborators: name: UConn Health
name: University of Alabama at Birmingham
First posted: 2017-04-07
Enrollment: 40
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized assignment to group will be in a 1:1 ratio utilizing block randomization in blocks of 10 to receive Prevnar-13 or Pneumovax 23. Following randomized assignment of vaccine, the study will be open-label.
Primary purpose: BASIC_SCIENCE

Brief summary: This is a prospective, single-site, randomized, then open-label study designed to develop a detailed transcriptional and epigenetic profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults.

In this study, 40 healthy adults ages 60 and older that have never received pneumococcal vaccination, will be randomized in a 1:1 ratio to receive Prevnar-13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Following randomized assignment of vaccine, the study will be open-label.

Six (6) study visits will occur over about 70 days, with an optional 7th visit for participants to receive a second vaccination with the other pneumococcal vaccine one to two years after randomization. Participants will provide blood samples for transcriptional, epigenetic and biological analyses pre- and post-vaccination.

Detailed description: This prospective, single-site, randomized, then open-label study is designed to develop a detailed transcriptional and epigenetic profile of the immune response to pneumococcal vaccination with conjugated and non-conjugated polysaccharide vaccines in the senescent immune system of older adults. This knowledge may lead to development of more effective vaccines through increased understanding of the effects of immunosenescence on mechanisms of immune response to pneumococcal vaccination in older adults elderly.

Forty (40) healthy adults ages 60 and older that have never received pneumococcal vaccination, will be randomized in a 1:1 ratio to receive Prevnar-13 (Pfizer), a conjugated 13-valent vaccine or Pneumovax 23 (Merck), a non-conjugated 23-valent vaccine. Following randomized assignment of vaccine, the study will be open-label. The study sample will be drawn from the population of healthy older participants in the catchment area of UConn Health in Farmington, CT.

The first six (6) study visits are planned to occur over 67 days at Days -7, 0, 1, 10, 28 (±3 d) and 60 (± 5d). Participants will provide blood samples for transcriptional, epigenetic and biological analyses pre- and post-vaccination.

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with the vaccine that they did not receive by random assignment at Visit 2 (Day 0). This second vaccine will be provided at no charge to the participant. Administration of this vaccine will occur at an optional Visit 7 for participants who choose to receive the second vaccine and will be scheduled at the participant's convenience one-two years after receiving the first pneumococcal vaccine.

If the participant opts to receive the second vaccine within the study and attends optional Visit 7, blood samples for genomic and biologic analysis will be collected at the visit.

Eligibility criteria: Inclusion Criteria:

* Able and willing to provide written informed consent
* Male or Female, 60 years of age or older
* Willing to receive pneumococcal vaccination with Prevnar 13 (Wyeth/ Pfizer) or Pneumovax 23 (Merck), as randomly assigned.
* Available to attend 6 study visits over 67 days (Visit 7 is optional at Day 365-720).

Exclusion Criteria:

* Previous pneumococcal vaccination with Prevnar 13 or Pneumovax 23.
* History of anaphylactic/anaphylactoid or severe allergic reaction to any component of Pneumovax 23, Prevnar 13 or any diphtheria toxoid-containing vaccine.
* Established diagnosis of diabetes
* History of receiving Zostavax (shingles vaccine) within previous 4 weeks. (Study entry may be delayed to satisfy a 28-day interval between vaccinations)
* Known history of any of the following co-morbid conditions:

  * Malignancy (participants without a recurrence in the last 5 years will be allowed)
  * Congestive Heart Failure
  * Cardiovascular Disease (unstable ≤ 6 months\*)
  * Kidney disease
  * Renal failure
  * Impaired hepatic function
  * Autoimmune disease such as: Rheumatoid Arthritis, systemic lupus erythematosus (SLE), Inflammatory Bowel Disease, etc.
  * Use of medicines during past 6 months known to alter immune response such as high-dose corticosteroids
  * HIV, AIDS or other Immunodeficiency
  * Recent (≤ 3 months) trauma or surgery
  * Current substance and/or alcohol abuse \* Unstable disease is defined as a change in therapy or hospitalization for worsening disease.

Primary outcomes:
measure: Pneumococcal-specific Antibody Responses
timeFrame: 70 days
measure: Pneumococcal-specific Antibody Responses - Fold Change Post First Vaccination
timeFrame: 70 days
Secondary outcomes:
measure: Number of Genes Upregulated Following Vaccination With PCV13 or PPSV23
timeFrame: 10 days post first vaccination
measure: Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23
timeFrame: baseline and 10 days post first vaccination
Other outcomes:
Locations:
city: Farmington
country: United States
facility: UConn Center On Aging
state: Connecticut
Study officials:
affiliation: UConn Center on Aging
name: George Kuchel, M.D. F.R.C.P
role: PRINCIPAL_INVESTIGATOR
References: