Evaluation of Metabolic Predictors of Influenza Vaccine Immune Response in the Singapore Elderly Population - the DYNAMIC Trial

Study Overview
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Brief Summary
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The trial aims to evaluate role of metabolic factors including systemic 25-OH D and diabetes in the adaptive immune response (haemagluttination inhibition titer) to influenza vaccine in the elderly. The influenza vaccine administered in this study will be licensed trivalent inactivated influenza vaccine. Elderly who are age above 65 including those with co-morbidities such as diabetes mellitus will be included. The study has its inclusion and exclusion criteria to determine eligibility for participation.

Detailed Description
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Novel, effective influenza vaccination strategies are needed in the elderly who have the highest rate of influenza-related morbidity and mortality. Vaccine efficacy in the elderly is reduced due to immunosenescence and/or, inflamm-aging. This phase IV clinical trial in 240 participants aims to evaluate metabolic predictors of influenza-vaccine specific immune response in a multi-ethnic elderly community cohort in Singapore. Specifically, our novel approach is to evaluate the immunomodulatory roles of vitamin D, diabetes and other metabolic predictors. This study has translational implications (e.g. using vitamin D as an 'adjuvant', evaluating biomarkers of vaccine efficacy) to enhance influenza vaccine immunogenicity in the vulnerable elderly. Potential benefit: there is a possibility the vaccine may prevent influenza illness or influenza related complication that might have otherwise occurred. This study will contribute to body of knowledge of impact of metabolic factors (vitamin D, DM status) on influenza vaccine immune response, and will be the first study of its kind to be done in an Asian elderly population. Potential risks related to the blood draw and local/systemic side effects from influenza vaccine are anticipated to be minimal.

Official Title
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Evaluation of Metabolic Predictors of Influenza Vaccine Immune Response in the Singapore Elderly Population- the DYNAMIC Trial

Conditions
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Immune Response, Elderly, Vitamin D Deficiency, Metabolic Disease, Influenza Vaccine, Diabetes Mellitus

Intervention / Treatment
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* Biological: Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 65 and above at time of enrollment (up to age 100) and able to give informed consent Determined by medical history, physical examination, and clinical judgment to be generally healthy, with no immunosuppressive conditions and having stable current medical conditions. Subjects with preexisting, stable disease, defined as not requiring significant change in therapy or hospitalization for worsening of disease 12 weeks prior to receipt of study vaccine are eligible. A change in dose or therapy within a treatment category (e.g., change from one non-steroidal anti-inflammatory drug to another) is allowed. A change to a new therapy category (e.g., surgery or addition of a new pharmacological class) is only allowed if it is not caused by worsening disease. Is eligible for seasonal influenza vaccine Is available for all planned study visits Is willing to follow study procedures Able to follow study procedures (questionnaires, blood draws, vaccination) in the opinion of the investigator Exclusion Criteria: A change to a new therapy category caused by worsening disease is considered significant and will disqualify subject from participating in the study Subjects reporting any symptoms suggestive of influenza, influenza-like illness, or respiratory illness Vaccination with any licensed or experimental influenza vaccine within the past 10 months Intent to receive any other investigational vaccine or agent during the course of the study Intent to receive other licensed vaccines during the course of the study (does not apply for pandemic or post-exposure prophylaxis scenario History of severe adverse reaction associated with an influenza vaccine Allergic to egg proteins (egg or egg products) and chicken proteins Known or suspected immunodeficiency or receiving treatment with immunosuppressive therapy including cytotoxic agents in past 6 months e.g., transplant recipients on active immunosuppression, patients with cancer, HIV, or autoimmune disease. Long-term systemic corticosteroid therapy (prednisolone ≥ 7.5mg/day or equivalent for more than 2 consecutive weeks within the past 3 months) Note: If systemic corticosteroids have been administered short term for treatment of an acute illness, subjects will be excluded from the study until corticosteroid therapy had been discontinued for at least 30 days. History of Guillain-Barré syndrome Serious chronic medical condition including: metastatic malignancy, severe chronic obstructive pulmonary disease requiring supplemental oxygen, CKD stage 3 and above, end stage renal disease with or without dialysis, clinically unstable cardiac disease, or any other disorder that in the investigator's opinion should preclude the subject from participating in the study Bariatric surgery, GI malabsorption disorders Recurrent Falls (≥2 falls in the past 12 months) Osteoporosis with or without pathological fractures Current or recently completed high dose vitamin D supplementation within the past 3 months (defined as daily cholecalciferol dose of 2000 IU or higher, weekly 50,000 IU or intramuscular calcitriol) Receipt of any blood products, including immunoglobulin, within six months of study enrollment Donated blood within last 58 days Current anticoagulant therapy or a history of bleeding diathesis (including thrombocytopenia with platelet count < 50,000) that would contraindicate intramuscular (IM) injection (Note: antiplatelet drugs such as aspirin and clopidogrel are permitted) Moderate or severe acute illness/infection (according to investigator judgement) on the day of vaccination, or febrile illness (temperature ≥ 37.5°C). A prospective subject should not be included in the study until the condition has resolved or the febrile event has subsided. Any medical condition that would, in the opinion of the investigator, interfere with the evaluation of the study objectives

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ≥ 65 Years old<br>Healthy community-dwelling elderly (men and women) age 65 and above who are eligible for influenza vaccine and fulfil inclusion and exclusion criteria | Biological: Influenza Vaccine<br>* Inactivated Trivalent Influenza Vaccine (IIV3) 2017 containing: A (H1N1): an A/Michigan/45/2015 (H1N1) - like virus (new strain); A (H3N2): an A/Hong Kong/4801/2014 (H3N2) - like virus; B/Brisbane/60/2008 - like virus<br>* Other names: Influvac(R) SH 2017;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response measure | Haemagglutination inhibition (HAI) titer for each of the three influenza vaccine strains in response to influenza vaccine at day 28 compared to baseline (pre-vaccination) titer | Day 0 to Day 28 post vaccination |