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The Immune Response to Influenza Vaccinations in Elderly Individuals

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ClinicalTrials.gov Identifier: NCT03266237
Recruitment Status : Completed
First Posted : August 30, 2017
Last Update Posted : August 30, 2017
Sponsor:
Collaborators:
National University, Singapore
Agency for Science, Technology and Research
Sanofi Pasteur, a Sanofi Company
Information provided by (Responsible Party):
National University Hospital, Singapore

Brief Summary:
The aim of this study is to characterize the immune profile of frail and healthy aged individuals and investigate their immune responsiveness including the response to influenza vaccine over an 18-month period. The project will include a longitudinal study to define immune signatures and multi-parameter profiles associated with frailty and may lead to the identification of predictive markers of evolution to frailty and Immunosenescence in the elderly.

Condition or disease Intervention/treatment Phase
Influenza Drug: Vaxigrip® Phase 4

Detailed Description:
With better healthcare available and improved accessibility, people are living longer. However, a majority of older persons cannot be considered to be aging well. Approximately 70% of those aged 85 years or older require frequent long hospitalizations because of their increased susceptibility to infections, cancers, dementia, and other age-related health problems, along with overall loss of function and autonomy associated with old age. Previous studies have shown that vaccination against influenza, which significantly reduces all-cause mortality in the elderly (65 years and older), was less immunogenic and effective with age. Frailty, a geriatric syndrome associated with low functional activity, weight loss, exhaustion, disability, decreased resilience to stressors, has been shown to increase risk for adverse outcomes and death. Better understanding the relationship between aging and waning immune responsiveness will enable the development of strategies to improve response to vaccination in the elderly and reduce morbidity and eventually mortality associated with age related complications and outcomes such as infectious diseases or frailty. A comprehensive analysis of the immune phenotype and function after antigenic challenge in older individuals would be a unique approach to understand (i) the potential associations between aging, impaired immune function and transition to frailty, (ii) which components of the immune system are altered with aging (innate vs adaptive immunity) and (iii) if early and/or late immune responses are preferentially altered with aging and frailty.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Multi-parameter Immune Profile Associated With the Humoral Response to Influenza Vaccine, Vaxigrip® in Healthy and Frail Elderly Subjects Aged 65-90 Years in Singapore
Study Start Date : December 2013
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Flu Flu Shot

Arm Intervention/treatment
Experimental: Healthy Adult
Healthy adult participants aged 21-40 years will be vaccinated with Vaxigrip® influenza vaccine
Drug: Vaxigrip®
To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.

Experimental: Healthy Elderly
Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
Drug: Vaxigrip®
To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.

Experimental: Healthy Elderly Pre-Frail
Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
Drug: Vaxigrip®
To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.

Experimental: Healthy Elderly Frail
Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
Drug: Vaxigrip®
To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.




Primary Outcome Measures :
  1. The Immune Responsiveness of Elderly Subjects when Administered Influenza Vaccination as Measured by HAI [ Time Frame: 18-month period ]
    Hemagglutination Inhibition (HAI) titer


Secondary Outcome Measures :
  1. Cellular Immune Response and Inflammatory Profile of elderly subjects when administered influenza vaccination - Flu-Specific T cells [ Time Frame: 18 months ]
    % Flu-specific T cells out of total PBMCs

  2. Flu-Specific B Cell Response [ Time Frame: 18 months ]
    No. of flu-specific B cells quantified out of 1x105 PBMCs

  3. Inflammatory Markers [ Time Frame: 18 months ]
    Quantitative (pg/mL analyte, picogram of analyte per milliliter of plasma)


Other Outcome Measures:
  1. Clinical Assessments of the elderly subjects - Weight [ Time Frame: 18 months ]
    Quantitative Weight (kg, kilograms)

  2. Clinical Assessments of the elderly subjects - Height [ Time Frame: 18 months ]
    Quantitative Height (m, meters)

  3. Clinical Assessments of the elderly subjects - BMI [ Time Frame: 18 months ]
    Quantitative BMI (weight and height will be combined to report in kg/m2)

  4. Clinical Assessments of the elderly subjects - DXA [ Time Frame: 18 months ]
    Quantitative Dual-Energy X-Ray Absorptiometry (DXA) scan: Standardized Muscle Index (appendicular lean mass / height-squared); T-score based on Bone Mineral Density BMD (appendicular lean mass and height will be combined to report in g/cm2)



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Aged ≥ 65 years and <90 years on the day of inclusion for the elderly group, and ≥ 21-<40 for the adult group.
  2. Informed consent form has been signed and dated.
  3. Able to attend all scheduled visits and to comply with all trial procedures.
  4. Living at home.
  5. Able to walk without personal assistance and no other physical limitations that can limit participation.
  6. Recruited from the cohort in Singapore Longitudinal Ageing Study-II (SLAS-II), as well as from sites in West Jurong and from Outpatient clinics at National University Hospital (NUH).

Exclusion Criteria:

  1. Participation at the time of study enrollment (or in the 4 weeks preceding trial vaccination) or planned participation during the present trial period in another clinical trial investigating vaccine, drug, medical device, or medical procedure.
  2. Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following trial vaccination, including influenza vaccination. However, 23-valent pneumococcal vaccine and tetanus vaccine will be allowed during this time window.
  3. Receipt of an influenza vaccine within the 6 months preceding the trial vaccination or planned influenza vaccination during the trial.
  4. Known or suspected congenital or acquired immunodeficiency or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
  5. Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components or a history of a life-threatening reaction to Vaxigrip® or to a vaccine containing any of the same substances.
  6. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
  7. Current alcohol or drug addiction.
  8. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
  9. Identified as an Investigator or employee of the Investigator or study centre with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse) of the Investigator or employee with direct involvement in the proposed study.
  10. Severe audio-visual impairment.
  11. Dementia, severe cognitive impairment (MMSE <18), major depression or other psychotic disorders.
  12. Progressive, degenerative neurologic disease: e.g. Alzheimer's disease.
  13. Rapidly progressive or terminal illness under palliative care with life expectancy less than 12 months.
  14. Primary severely muscle/joint disorders resulting in physical disability interfering with the physical performance tests needed for the study.
  15. Hospital admission in the past 6 weeks.
  16. (Relevant for the healthy young adults subjects group). Subject is pregnant (or positive urine pregnancy test), or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be postmenopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination).
  17. Self-reported thrombocytopenia, contraindicating intramuscular vaccination
  18. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding vaccination, contraindicating intramuscular vaccination upon investigator's judgement.

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): NCT03266237


Locations
Singapore
Moral Neighbourhood Link @ Telok Blangah
Singapore, Singapore, 090003
National University Hospital
Singapore, Singapore, 119228
THK Seniors Activity Centre @ Henderson (Satellite 93)
Singapore, Singapore, 150093
Moral Neighbourhood Link (Bukit Merah View)
Singapore, Singapore, 150118
THK Seniors Activity Centre @ Beo Crescent
Singapore, Singapore, 160044
SARAH Senior Activity Centre
Singapore, Singapore, 160105
THK Seniors Service @ Taman Jurong
Singapore, Singapore, 610337
TaRa @ Jurong Point, Jurong West Central 2
Singapore, Singapore, 648886
Outpatient Clinic, St Luke's Hospital
Singapore, Singapore, 659674
Sponsors and Collaborators
National University Hospital, Singapore
National University, Singapore
Agency for Science, Technology and Research
Sanofi Pasteur, a Sanofi Company
Investigators
Principal Investigator: Professor Paul Anantharajah Tambyah, MD National University, Singapore

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National University Hospital, Singapore
ClinicalTrials.gov Identifier: NCT03266237     History of Changes
Other Study ID Numbers: 2012/01214
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: August 30, 2017
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Publication of the data in peer-reviewed journals
Supporting Materials: Study Protocol
Time Frame: five years approx
Access Criteria: through a research agreement

Keywords provided by National University Hospital, Singapore:
Influenza
Influenza Virus Vaccines
Vaxigrip
Respiratory Tract Infections
Orthomyxoviridae Infections
Frailty
Aging
Safety
Immunogenicity

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs