Influence of Persistent CMV-infection on Immune Senescence

Sponsor

University of Zurich (Other)

Overall Status

Completed

CT.gov ID

NCT00461695

Collaborator

Division of Infectious Diseases and Hospital Epidemiology (Other)

183

Enrollment

Location

Arms

Duration (Months)

4.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recent studies indicate that persistent viral infections particularly with Cytomegalovirus (CMV) might have a negative impact on immune senescence (i.e. immunocompetence of elderly individuals). We will test this hypothesis by performing a vaccination trial in healthy elderly individuals subdivided in two groups of CMV-seropositive and CMV-seronegative individuals. All individuals will be vaccinated with the currently licensed vaccine for the prevention of TBE (FSME Immun CC) which is recommended for the general population in our area. Vaccination efficacy will be monitored longitudinally concerning the TBEV-specific antibody (TBEV-neutralization, TBEV-specific ELISA) and T cell response (ELISpot, cytokine production).

Vaccination efficacy will be compared between CMV+ and CMV- individuals and correlated with the CMV-specific immune response in CMV+ individuals.

Condition or Disease	Intervention/Treatment	Phase
Immune Senescence	Biological: Vaccination against TBEV (FSME Immun CC)	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

183 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Influence of Persistent CMV-infection on Immune Senescence Evaluated With a Prospective Vaccination Trial Against Tick-borne Encephalitis Virus in Healthy Elderly Individuals (CYTEL-Study)

Study Start Date :

May 1, 2007

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Other: CMV-seropositive Cytomegalovirus-seropositive individuals at screening (week 0). Intervention: Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.	Biological: Vaccination against TBEV (FSME Immun CC) Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.
Other: CMV-seronegative Cytomegalovirus-seronegative individuals at screening (week 0). Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.	Biological: Vaccination against TBEV (FSME Immun CC) Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.

Arm

Intervention/Treatment

Other: CMV-seropositive

Cytomegalovirus-seropositive individuals at screening (week 0). Intervention: Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.

Biological: Vaccination against TBEV (FSME Immun CC)

Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.

Other: CMV-seronegative

Cytomegalovirus-seronegative individuals at screening (week 0). Intervention: Vaccination against tick-borne encephalitis by intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.

Biological: Vaccination against TBEV (FSME Immun CC)

Intramuscular injection into the left (or right) deltoid muscle of 0.5 ml FSME Immun CC for adults (2.4 ug of formalin inactivated TBEV antigen) at time point 0, after 4 weeks and after 24 weeks.

Outcome Measures

Primary Outcome Measures

Geometric mean titer (GMT) of anti-TBEV-antibodies measured by TBEV-neutralisation assay and ELISA one month after each TBEV-vaccine administration in the group of CMV-seropositive versus CMV-seronegative individuals [One month after each TBEV-vaccine administration]

Secondary Outcome Measures

Efficacy of TBEV-vaccination in healthy elderly individuals (Geometric mean antibody titer measured by TBEV-neutralisation test). [One month after 3rd TBEV-vaccine administration]
Safety of TBEV-vaccination in healthy elderly individuals. [One month after 3rd TBEV-vaccine administration.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Age > 70 years
Healthy according to a health questionnaire (completed before screening)
TBE-Vaccination indicated (exposure to TBEV-infested ticks possible)
Capable to make an informed decision and to understand the informed consent form
Informed consent signed by patient and study physician

Exclusion criteria:

Previous exposure to TBEV (natural or vaccination)
Immunodeficiency, history of autoimmune disease or current intake of immune-modulating drugs (corticosteroids a.s.o.)
Persistent (> 3 months) pharmacological treatment with more than one drug of relevance (exception: combination antihypertensives)
Contraindication for TBEV-vaccination
Condition that would drastically interfere with clinic attendance and/or adherence to the protocol
Past medical history or current treatment for one of the following conditions: Chronic cardiac disease (Coronary heart disease, heart failure), chronic pulmonary disease (COPD), chronic kidney disease, diabetes mellitus, previous stroke, epilepsy, Parkinsons disease, dementia
Hemoglobin <12 g/l
Random plasma glucose (RPG) > 11.1 mmol/l OR fasting plasma glucose (FPG) > 6.9 mmol/l (FPG required, if RPG is 7.0-11.0 mmol/l)
Calculated Creatinin-Clearance < 50 ml/min
TBEV-serology positive