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Health Condition(s) or Problem
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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
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Lay Summary
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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. (from UKCRN Portfolio)
Additional lay summaries...
Background and study aims?
Flu is a major health concern and although flu vaccination is given every year to people over the age of 65 years, a lot of people make a poor immune response to the vaccine.
It is now clear that one reason why older people can develop problems with their immune system (body?s protectio¬n mechanism to defend against microbes, bacteria, viruses) is that they carry chronic viral infections such as cytomegalovirus (CMV). The immune system has to work very hard to control these infections and this ?diverts? them away from new infections such as flu.
We propose to use drugs that fight viruses known as anti-viral drugs (often used to treat diseases such as cold sores) to lessen the strength of CMV and therefore allow the immune system to recover from fighting the virus. We anticipate that the immune system will then make a stronger response to flu vaccination.
In the first part of the study we will find the dose that works best and see how long it needs to be taken for. In the second part we will use this dose in a larger group of patients receiving their flu vaccine. We will therefore test if this treatment works well. If proven, this treatment could be valuable in a wide range of clinical conditions and could help to promote healthy ageing.
Who can participate?
To take part you need to be aged over 65 and a healthy volunteer.
What does the study involve?
Part One:
If you take part, you will be asked to give a small sample of blood taken for testing in the lab to check if you are eligible to take part in this study. If you are eligible then you will be contacted by the ASPIRE team and invited back to another clinic at your surgery. A member of the team will discuss the study with you again and check that there have been no changes to your health or any medication you are currently taking. You will then be asked to sign another consent form before donating a blood and urine sample for baseline analysis.
A computer will decide at random (like rolling a dice) what dose of the treatment drug you will be prescribed. Your GP will prescribe the medication the computer chooses for you using a standard prescription that can be collected from one of our designated pharmacies, and this medication needs to be taken every day for the prescribed length of time (three or six months).
Over the course of the next six months, your GP or practice nurse will see you at monthly intervals to complete a questionnaire, collect blood and urine samples and prescribe the following month?s medication. In addition to this, you will be seen at two follow-up clinics; nine months after entering the study and again after 12 months.
Part Two:
If you take part, you will be asked to give a small sample of blood taken for testing in the lab to check if you are eligible to take part in this study. If you are eligible then you will be contacted by the
ASPIRE team and invited back to another clinic at your surgery. A member of the team will discuss the study with you again and check that there have been no changes to your health or any medication you are currently taking. You will then be asked to sign another consent form before donating a blood sample for baseline analysis.
A computer will decide at random which type of treatment you will have. Half of the people taking part will be prescribed the medication and the other half will be prescribed a placebo capsule (a placebo tablet looks exactly the same as the active medication but contains no active drug). Your GP will prescribe the medication the computer chooses for you using a standard prescription that can be collected from one of our designated pharmacies, and this medication needs to be taken every day for the prescribed length of time (three months).
After two months an appointment will be made at your surgery to have a seasonal flu vaccination. At this point a further blood sample will be taken and questionnaire completed. Over the course of the next four mon (from ISRCTN)
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Who can enter the trial
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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
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Who cannot enter the trial
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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
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What will happen
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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
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Primary aim
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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
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Secondary Aim
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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
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Participant Information Sheet
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Not available in web format, please use the contact details below to request a patient information sheet
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Website
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Sorry, not currently available
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Recruitment Status
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Recruiting
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Nation
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England
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Location
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Birmingham
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