ASPIRE - A study promoting the influenza response in the elderly

Flu jab being administered with elderly patientVaccination against influenza (‘flu’) is surprisingly unsuccessful, with many people failing to achieve the desired immunity after receiving their flu jab. This is a big problem in elderly individuals, for whom flu can be life-threatening. In addition the recent emergence of ‘swine flu’ has increased the danger of a new pandemic, meaning influenza remains a global health concern.

One reason that we develop immune ‘frailty’ as we age is that our bodies have to invest a lot of resources into fighting viruses that build up in us throughout our lives. One of these viruses is Cytomegalovirus, a member of the herpesvirus family.

In this clinical trial we will use medicine to reduce the amount of virus in the body, thereby decreasing the need for the body to fight this infection. We will test whether this in turn causes response to flu vaccination to improve. The study tackles a major clinical concern for UK health and could have major implications for the management of immune dysfunction in the elderly.

Design

This study is a two-phased randomised controlled trial. Part one will consist of a dose-finding study for the use of valaciclovir in suppression of the CMV-specific immune response. Once this information has been established we will implement the optimum dose and determine whether it leads to an improvement in the response to the seasonal flu vaccination in elderly people.

Aim of study

Phase I: The primary objective is to determine the efficacy of valaciclovir for reduction of both the CD4+ and CD8+ CMV-specific T cell responses.

Phase II: Aim is to assess the value of valaciclovir in the augmentation of the immune response to influenza vaccination in donors aged ≥65 years. This will then provide evidence as to whether a larger trial with clinical end points is justified.

Setting

This study will take place in the primary care setting, recruiting patients from NHS GP surgeries across Birmingham and the Black Country. Additionally, participants will be recruited from the Thousand elders groups of volunteers with the Wellcome Trust Clinical Research Facility being used to host clinics for these participants.

Target population

Healthy people aged 65 years and above, without significant chronic illness and not taking certain medication including antivirals. Patients that fill these criteria will be screened, and if their blood tests pass various laboratory tests they will be eligible.

What the samples are being used for

At screening, blood samples are being used for several assays to test for eligibility for participation in the trial. At trial time points, blood samples will be used in assays to produce primary and secondary outcomes (i.e. data that will form the results of the trial). A urine sample will also be taken at each time point, which will be used to measure the level of viral DNA.