The Immune Response to Influenza Vaccinations in Elderly Individuals

Influenza Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03266237
• Other study ID #: 2012/01214
• Status: Completed
• Phase: Phase 4
• First received: September 20, 2016
• Last updated: August 27, 2017
• Start date: December 2013
• Est. completion date: May 2016

Study information

• Verified date: October 2016
• Source: National University Hospital, Singapore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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.

Locations

Country	Name	City	State
Singapore	Moral Neighbourhood Link (Bukit Merah View)	Singapore
Singapore	Moral Neighbourhood Link @ Telok Blangah	Singapore
Singapore	National University Hospital	Singapore
Singapore	Outpatient Clinic, St Luke's Hospital	Singapore
Singapore	SARAH Senior Activity Centre	Singapore
Singapore	TaRa @ Jurong Point, Jurong West Central 2	Singapore
Singapore	THK Seniors Activity Centre @ Beo Crescent	Singapore
Singapore	THK Seniors Activity Centre @ Henderson (Satellite 93)	Singapore
Singapore	THK Seniors Service @ Taman Jurong	Singapore

Sponsors (4)

Lead Sponsor	Collaborator
National University Hospital, Singapore	Agency for Science, Technology and Research, National University, Singapore, Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Clinical Assessments of the elderly subjects - Weight	Quantitative Weight (kg, kilograms)	18 months
Other	Clinical Assessments of the elderly subjects - Height	Quantitative Height (m, meters)	18 months
Other	Clinical Assessments of the elderly subjects - BMI	Quantitative BMI (weight and height will be combined to report in kg/m2)	18 months
Other	Clinical Assessments of the elderly subjects - DXA	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)	18 months
Primary	The Immune Responsiveness of Elderly Subjects when Administered Influenza Vaccination as Measured by HAI	Hemagglutination Inhibition (HAI) titer	18-month period
Secondary	Cellular Immune Response and Inflammatory Profile of elderly subjects when administered influenza vaccination - Flu-Specific T cells	% Flu-specific T cells out of total PBMCs	18 months
Secondary	Flu-Specific B Cell Response	No. of flu-specific B cells quantified out of 1x105 PBMCs	18 months
Secondary	Inflammatory Markers	Quantitative (pg/mL analyte, picogram of analyte per milliliter of plasma)	18 months