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Pneumococcal Conjugate Vaccine in Aging Renal Transplant

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ClinicalTrials.gov Identifier: NCT03802994
Recruitment Status : Recruiting
First Posted : January 14, 2019
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
The goal of the research proposed in the current application is to first define how much antibody aging renal transplant and dialysis recipients make after they are vaccinated with the pneumonia vaccine and how this compares to similar aged persons with good renal function and healthy young adults. The investigators will study differences in the kind of B cells and markers on the B cells that are known to be important in the response to the pneumonia vaccine in aging renal transplant and aging dialysis recipients compared to similarly aged and young healthy controls. Finally, the investigators will study how safe the pneumonia vaccine is in aging renal transplants. The answers to these questions will help in designing a better vaccine for older people with a renal transplant or on dialysis.

Condition or disease Intervention/treatment Phase
Renal Transplantation Aging Drug: 23 valent pneumococcal polysaccharide vaccine Biological: 13 valent conjugated pneumococcal vaccine Other: Peripheral blood sample Early Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Immune response to immunization with Prevnar in elderly aging renal transplant compared to comparison groups: healthy young, healthy elderly, healthy elderly hypertension (HTN) and young renal transplants.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immune Response to Pneumococcal Vaccination in Aging Renal Transplant Recipients
Actual Study Start Date : November 1, 2018
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aging RT
Renal transplant recipients between 65-75 years of age, on stable immunosuppression. who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23). Cause or renal failure was either DMII or HTN.
Other: Peripheral blood sample
Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.
Other Name: blood draw

Active Comparator: Elderly DM II and/or HTN, normal renal function
Persons with DMII or hypertension but normal renal function between ages 65-75 years of age
Other: Peripheral blood sample
Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.
Other Name: blood draw

Active Comparator: Healthy elderly
Healthy persons between the ages 65-75 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)
Other: Peripheral blood sample
Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.
Other Name: blood draw

Active Comparator: Elderly DMII or HTN and normal renal function
Persons between the ages 65-75 with DMII or hypertension but normal renal function who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23)
Other: Peripheral blood sample
Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.
Other Name: blood draw

Experimental: Healthy young
Healthy persons between the ages 35-45 who previously (>1 year prior) received the 23 valent pneumococcal polysaccharide vaccine (pneumovax23) or are willing to receive PPV23 and 1 year later Prevnar 13.
Drug: 23 valent pneumococcal polysaccharide vaccine
FDA approved pneumococcal polysaccharide vaccine containing capsular polysaccharide of 23 different pneumococcal serotypes. Only group 5 will potentially receive this as an intervention.
Other Name: Pneumovax 23 or PPV23

Biological: 13 valent conjugated pneumococcal vaccine
FDA approved pneumococcal polysaccharide vaccine containing capsular polysaccharide of 13 different pneumococcal serotypes conjugated to CRM197. Only group 5 will receive this as an intervention. In all other groups Prevnar 13 will be given as standard of care.
Other Name: Prevnar 23 or PCV13

Other: Peripheral blood sample
Peripheral blood samples (30-60 mL) will be collected at day 0 (pre-immune), day 7, and day 30 (4 weeks post-PPV23) for groups 1-4 and at days 366, 373 and 396 for group 5. In addition, day 5, and 10 blood samples will be obtained from a limited (n=10) number of elderly RT participants to determine the optimal time point for circulation of PPS-specific B cells. Yearly blood samples will be obtained thereafter for serum antibody and OPA analyses to test longevity of antibody and OPA responses. Samples obtained from days 0, 30 and yearly samples will be used for antibody titers and opsonophagocytic assays. Samples from day 0 (day of vaccination with PCV13) and day 7 will be used for flow cytometric analysis.
Other Name: blood draw




Primary Outcome Measures :
  1. anti-pneumococcal IgG antibody (ug/ml) change [ Time Frame: Baseline, 1 month, 12 months and 2 years ]
    Measure the anti-pneumococcal polysaccharide IgG antibody response against streptococcus pneumonia serotypes 14, 19A and 23F in serum by ELISA at days 0, 30, 365 and 720

  2. Opsonophagocytic antibody titer serum dilution change [ Time Frame: Baseline, 1 month, 12 months and 2 years ]
    Measure the serum opsonophagocytic activity against streptococcus pneumonia serotypes 14, 19A and 23F on days 0, 30, 365 and 720 by opsonophagocytic assay.

  3. number of polysaccharide specific B cells (cells/mL) [ Time Frame: day 7 ]
    number of polysaccharide specific B cells, and absolute number of IgM memory B cells/mL induced by vaccination with PCV13


Secondary Outcome Measures :
  1. relative gene expression/cell (change in copy numbers) change [ Time Frame: Baseline and 1 week ]
    Measure the relative gene expression of 56 genes important in antibody production and cell survival per single cell of polysaccharide-specific and non-specific B cells as measured by QTR PCR.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Inclusion criteria are group specific. HBV, HCV and HIV testing are not necessary in the RT groups as all RT recipients are tested prior to transplant. The investigators will not restrict volunteers with respect to gender, ethnic or racial group.

Groups 1 (65-75 yrs) and 2 (35-45 yrs) Renal Transplant populations

  • End stage renal disease cause either DM2 and/or hypertension (HTN)
  • Renal transplant >12 months ago

Group 3: Diabetic/hypertensive 65-75 year old controls

  • With DM2 and/or HTN
  • Previous immunization with PPV23 >1 year prior
  • Willingness to be tested for HIV, HBV and HCV
  • "normal kidney function" defined as glomerular filtration rate (GFR) of 60% or above

Group 4: Healthy Control 65-75 yr old

  • Without DM2
  • May have high blood pressure (systolic>140 and/or diastolic>90) as long as it is well controlled (systolic<140 and/or diastolic <90) and has not affected kidney function.
  • Previous receipt of PPV23 > 1 year prior
  • Willingness to be tested for HIV, HBV and HCV

Group 5: Healthy Control 35-45 yr old

  • Without DM2.
  • May have high blood pressure (systolic>140 and/or diastolic>90) as long as it is well controlled (systolic<140 and/or diastolic <90) and has not affected kidney function.
  • Willingness to be tested for HIV, HBV and HCV and filling out a medical questionnaire that will include diabetes screening.

Exclusion Criteria:

Exclusion criteria are either applicable to all groups or group specific. Therefore we have listed the exclusion criteria applicable to ALL groups first. Group specific criteria are listed under each group.

Exclusion Criteria common to all groups

  • Previous immunization with PCV13.
  • Pregnancy, no contraceptive practice in women of childbearing age, or breastfeeding
  • Known anaphylaxis, hypersensitivity or "bad allergic reaction" to the pneumonia vaccine. This does not include egg allergy or previous Guillan Barre syndrome.
  • Those who received blood products or gamma globulin within 3 months.
  • Inability to comprehend or sign the informed consent form
  • Previous/present illness that may affect immune response to the vaccine

    • previous pneumococcal disease
    • disease
    • removal of the spleen
    • auto-immune disease such as lupus or rheumatoid arthritis
    • end-stage liver disease
    • cancer
  • Significant abnormalities (3xULN and all those considered to be critical values) in CBC, chemistries including glucose.
  • HIV, HBsAg or HCV positivity
  • Receipt of PPV23 within 1 year

Groups 1 (65-75 yrs) and 2 (35-45 yrs) Renal Transplant populations

  • Medications that are known to affect immune function (chemotherapy, anti-TNF agents) with the exception of anti-rejection medication.
  • Episode of acute rejection within the last 6 month period

Group 3: Diabetic/hypertensive 65-75 year old controls

  • Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
  • The inclusion/exclusion criteria will be determined by chart review.

Group 4: Healthy Control 65-75 yr old

  • Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
  • The inclusion/exclusion criteria will be determined by chart review and pregnancy test for females of child bearing potential.

Group 5: Healthy Control 35-45 yr old

  • Medications that are known to affect immune function (chemotherapy, anti-TNF agents).
  • The inclusion/exclusion criteria will be determined by chart review and pregnancy test for females of child bearing potential.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03802994


Contacts
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Contact: M.A. J Westerink, MD (843) 577-5011 ext 7292 maria.westerink@va.gov
Contact: Myraslawa Soloshchenko, BS (843) 792-9799 soloshch@musc.edu

Locations
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United States, South Carolina
Ralph H. Johnson VA Medical Center, Charleston, SC Recruiting
Charleston, South Carolina, United States, 29401-5799
Contact: Rutha A LaRue    (843) 789-6713    Rutha.Larue@va.gov   
Contact: Sarah A Jackson, BA MA    (843) 789-6700    sarah.jackson@va.gov   
Principal Investigator: M.A. Julia Westerink, MD         
Medical University of South Carolina Recruiting
Charleston, South Carolina, United States, 29425
Contact: Maria Westerink, MD    843-792-9799    westerin@musc.edu   
Contact: Myraslawa Solshchenko, BS    8437922218    solshch@musc.edu   
Sponsors and Collaborators
VA Office of Research and Development
Investigators
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Principal Investigator: M.A. Julia Westerink, MD Ralph H. Johnson VA Medical Center, Charleston, SC

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Responsible Party: VA Office of Research and Development
ClinicalTrials.gov Identifier: NCT03802994     History of Changes
Other Study ID Numbers: INFB-019-17F
CX001568 ( Other Grant/Funding Number: VA CSR&D )
First Posted: January 14, 2019    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes

Keywords provided by VA Office of Research and Development:
Prevnar
pneumococcal conjugate vaccine
aging
renal transplant recipient

Additional relevant MeSH terms:
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Vaccines
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs