Investigating the Immune System in chrONIC Kidney Disease. (SONIC)

Investigating the Immune System in chrONIC Kidney Disease - the SONIC Study.

This study will investigate the function of the immune system in people with chronic kidney disease (CKD) compared to people with normal kidneys. The investigators will use standard vaccines - the seasonal flu vaccine and pneumococcal polysaccharide (Pneumovax) vaccine - to examine how the immune system responds to challenge. All subjects will receive these recommended vaccines as part of routine care. Blood and urine samples will be collected and tested at different time points to look at how the immune response develops to these vaccines and if there are any differences between people with CKD and those without. This will help us understand how CKD affects the function of the immune system.

Study Overview

• Status: Unknown
• Conditions: Immune System Diseases; Chronic Kidney Disease
• Intervention / Treatment: Biological: Seasonal influenza and pneumococcal polysaccharide vaccines

Detailed Description

Compared to the general population, people with CKD are known to get more infections and are more likely to have complications from them. Protective measures such as vaccinations for common infections are not as effective in patients with CKD as they are in people with healthy kidneys. The reasons why this happens are not very clear. It is known that with increasing age, the body's immune defences are weakened, but it is not yet clear how different this is in older people with CKD compared to older people with healthy kidneys. Understanding how CKD affects the body's immune defence to new infections is vital in helping to prevent severe consequences from infection and make vaccination more effective for this group of people. This project aims to look at the function of immune cells in CKD patients and people with normal kidney function, together with their responses to clinically recommended vaccinations, including Pneumococcus (common pneumonia organism) and the influenza virus (the flu).

Study participants are invited to receive the clinically recommended seasonal influenza and pneumococcal polysaccharide vaccines during the seasonal influenza vaccination season (September - December), mirroring routine care they would receive in the community. Information on age, gender and pre-existing health problems, together with blood and urine samples will be collected from CKD patients for comparison with healthy volunteers at the following timepoints: day of vaccination, day 7 and 28 and 6 months after vaccination.

• Study Type: Observational
• Enrollment (Actual): 43

Contacts and Locations

Study Locations

• United Kingdom
  • West Midlands
    • Birmingham, West Midlands, United Kingdom
      • University Hospitals Birmingham NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

CKD patients - individuals attending local tertiary care nephrology clinics.

Healthy control subjects - individuals accompanying CKD patients to nephrology clinics or individuals invited to participate from Birmingham 1000 Elders Cohort.

Description

Inclusion Criteria:

• any gender
• aged 65 and over

Exclusion Criteria:

• Subjects who have had Pneumovax within last 5 years
• Subjects who have had current season's influenza vaccine
• CKD patients: eGFR less than 15ml/min or greater than 60ml/min, immune mediated cause of kidney disease.
• Healthy control subjects: known kidney disease, eGFR less than 60ml/min
• Subjects with comorbidities that are associated with an immunosuppressed state including, but not limited to, the following: Malignancy diagnosed within last 5 years except non-melanoma skin cancer; Solid organ (including kidney) or bone marrow transplant recipients; Blood borne viral infections: HIV, hepatitis B and C; Autoimmune disease e.g. vasculitis, rheumatoid arthritis; Previous splenectomy or asplenia from any other cause.
• Subjects currently taking any of the following immunosuppressive medications: Systemic corticosteroids e.g. prednisolone/dexamethasone; Chemotherapy agents e.g. cyclophosphamide, methotrexate, azathioprine; Biological therapies e.g. rituximab, infliximab, etanercept - including any administration within preceding 12 months.
• Subjects who have previously had a serious reaction to influenza vaccination, including anaphylaxis and Guillain-Barre Syndrome within 6 weeks of previous influenza vaccination
• Subjects who have a severe egg allergy (contraindication to influenza vaccination)
• Subjects who have previously had a serious reaction to the whole or any components of pneumococcal vaccination
• Subjects who have an active infection and/or are febrile on assessment

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Chronic Kidney Disease (CKD) patients; Any gender, aged 65 years and over. Chronic kidney disease with eGFR between 15 and 60 ml/min. No immunological cause of kidney disease. Not immunosuppressed. To receive both seasonal influenza and pneumococcal polysaccharide vaccines as part of recommended clinical care.	Biological: Seasonal influenza and pneumococcal polysaccharide vaccines; Vaccination
Healthy Control subjects; Any gender, aged 65 years and over. No known renal disease and eGFR 60ml/min or greater. Not immunosuppressed. To receive both seasonal influenza and pneumococcal polysaccharide vaccines as part of recommended clinical care.	Biological: Seasonal influenza and pneumococcal polysaccharide vaccines; Vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving adequate humoral response to either vaccine	as assessed by vaccine-specific serum IgG levels	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who maintain protective antibody titres to either vaccine at 6 months after vaccination	as assessed by vaccine-specific serum IgG levels	6 months
Relationship between eGFR and immune cell subsets following vaccination	investigatory outcome - will be assessed using flow cytometric techniques and established biochemical laboratory eGFR testing	6 months
Relationship between eGFR and reported infection rates	as assessed using established biochemical laboratory eGFR testing and participant reported infection-related events	6 months

Collaborators and Investigators

• Sponsor: University of Birmingham
• Collaborators: Wellcome Trust; University Hospital Birmingham NHS Foundation Trust
• Investigators: Principal Investigator: Lorraine Harper, University of Birmingham

Publications and helpful links

General Publications

• Wall N, Godlee A, Geh D, Jones C, Faustini S, Harvey R, Penn R, Chanouzas D, Nightingale P, O'Shea M, Richter A, Moss P, Cunningham A, Harper L. Latent Cytomegalovirus Infection and Previous Capsular Polysaccharide Vaccination Predict Poor Vaccine Responses in Older Adults, Independent of Chronic Kidney Disease. Clin Infect Dis. 2021 Aug 16;73(4):e880-e889. doi: 10.1093/cid/ciab078.

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: August 25, 2015
• First Submitted That Met QC Criteria: August 27, 2015
• First Posted (Estimate): August 28, 2015

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Immune System Diseases; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: RG_14-216