Enhancing immunity to influenza in elderly individuals through reversal of immune senescence mediated by herpes virus infection | Not Recruiting
Enhancing immunity to influenza in elderly individuals through reversal of immune senescence mediated by herpes virus infection
ASPIRE
Trial Source

Health Conditions
  • Topic: Primary Care Research Network for England, Inflammatory and Immune System
  • Subtopic: Not Assigned, Inflammatory and Immune System (all Subtopics)
  • Disease: Immunology and inflammation, All Diseases
Not Recruiting
Recruitment Status
ISRCTN24967173
Primary Trial ID Number
Summary
We intend to treat immunocompetent elderly individuals with the anti-viral drug valaciclovir in order to reduce the level of endogenous cytomegalovirus (CMV) replication. This is expected to subsequently reduce the magnitude of the CMV-specific immune response and therefore enhance immunity to other infections. This will be investigated by monitoring the immune response to influenza vaccination.
Primary Outcome Measures
  • The magnitude of the CMV-specific CD8+ T cell immune response.; Timepoint(s): Part One:
  • Screening
  • Baseline
  • Months 1,2,3,4,5,6,9,12
Secondary Outcome Measures
  • 1. Quality of Life; Timepoint(s): Part One: Baseline, Months 1,2,3,4,5,6,9,12
  • 2. The CMV viral load in urine.; Timepoint(s): Part One: Baseline, Months 1,2,3,4,5,6,9,12
  • 3. The improvement in proportion of individuals making an adequate response to seasonal flu; Timepoint(s): Part Two: 14, 21, 28, 120 days post-vaccination
  • 4. The magnitude of the CMV-specific CD4+ T cell immune response.; Timepoint(s): Part One: Screening, Baseline, Months 1,2,3,4,5,6,9,12
  • 5. The magnitude of the influenza-specific CD4+ T cell immune response.; Timepoint(s): Part Two: Baseline, Months 1 & 2, Vaccination - 14, 21, 28, 120 days post-vaccination
  • 6. The magnitude of the influenza-specific CD8+ T cell immune response.; Timepoint(s): Part Two: Baseline, Months 1 & 2, Vaccination - 14, 21, 28, 120 days post-vaccination
  • 7. The titre of the CMV-specific antibody response.; Timepoint(s): Part One: Screening, Baseline, Months 1,2,3,4,5,6,9,12
  • 8. The titre of the H1, H3 and influenza B antibodies.; Timepoint(s): Part Two: Baseline, Months 1 & 2, Vaccination - 14, 21, 28, 120 days post-vaccination
  • 9. Tolerability of the treatment.; Timepoint(s): Part One: Baseline, Months 1,2,3,4,5,6,9,12
Research Question
  • ASPIRE - A Study Promoting the Influenza Response in the Elderly. We intend to treat immunocompetent elderly individuals with the anti-viral drug valaciclovir in order to reduce the level of endogenous cytomegalovirus (CMV) replication. This is expected to subsequently reduce the magnitude of the CMV-specific immune response and therefore enhance immunity to other infections. This will be investigated by monitoring the immune response to influenza vaccination.
Design Type
Sorry, this information is not available
Ethics Approval
Leicestershire, Northamptonshire & Rutland Research Ethics Committee 1, First MREC approval date 14/02/2011, ref:11/H0406/10
Publications
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Countries of Recruitment
United Kingdom
Participant Sex
Both
Participant Age Range
Senior
Participant Type
Patient
Trial Sample Size
700
Participant Inclusion Criteria
  • 1. Aged 65 years or above (30% 65-74 yrs old, 70% aged over 75 yrs)
  • 2. Cytomegalovirus (CMV) seropositive
  • 3. CMV-specific CD8+ and CD4+ T cell response over 0.5% of T cell pool at randomisation
  • 4. Human leuckocyte antigen (HLA) type of HLA-A1, A2, B7 or B8
  • 5. Predicted epidermal growth factor receptor (eGFR) > 50ml/min
  • 6. Liver function tests (LFT) in normal range.; Target Gender: Male & Female ; Lower Age Limit 65 years
Participant Exclusion Criteria
  • 1. On the following medication : Steroids, ciclosporin, mycophenolate, probenecid, tacrolimus, theophylline
  • 2. Significant chronic illness as assessed by clinical team
  • 3. History of cardiovascular event in the last 6 months
  • 4. General practitoner (GP) considers inappropriate to take part
  • 5. Unable to provide written consent
Interventions
Valaciclovir Hydrocloride, Part One: 50 eligible patients will be randomised into five treatment arms and the optimal treatment dose and duration of valaciclovir to suppress CMV levels by 85% determined over six months of treatment and six months follow-up. Placebo, Part Two: Half of the eligible patients (110) will be randomly allocated to placebo treatment. The duration and timing of treatment will be designed to match the active treatment arm. Both arms will receive a seasonal influenza vaccine after treatment and the immune response they mount quantified. Part Two: Half of the eligible patients (110) will be randomly allocated to valaciclovir treatment. The dose, duration and timing of treatment will be determined from Part One. Both arms will receive a seasonal influenza vaccine after treatment and the immune r; Follow Up Length: 12 month(s); Study Entry : Registration and One or More Randomisations
Design Details
Sorry, this information is not available
Study Design
ASPIRE is a two-part study: Part One: Dose-finding study. Part Two: Phase II randomised controlled trial
Results Reporting
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Acronym
ASPIRE
Scientific Title
A randomised controlled trial aimed at enhancing immunity to influenza in elderly individuals through reversal of immune senescence mediated by herpes virus infection
Secondary Trial Identifying Number
10177
Website
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Study Funded By
Medical Research Council (MRC) (UK) (Grant Codes: 94820)
Funder Type
Sorry, this information is not available
Study Sponsored By
University of Birmingham (UK)
Study Also Sponsored By
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Primary Sponsor Type
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Secondary Sponsor Type
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Key Dates

Date of First Enrollment

01 Nov 2011

Recruitment End Date

01 Jan 2014

Trial End Date

01 Jan 2014

Date added to Registry

17 Aug 2011

Last Updated

27 Jun 2012