Can shingles vaccination reduce the risk of heart attacks, brain hemorrhage and dementia?

The purpose of the DAN-ZOSTER study is to investigate whether the shingles vaccine Shingrix® can reduce the risk of heart attacks, brain hemorrhage, cardiovascular death, and dementia in people aged 65 years or older.

If you have any questions, you can find answers at the bottom of the page under Questions and Answers. You are also welcome to call us at 88 30 01 02 on weekdays between 9:00 a.m. and 3:00 p.m.

Shingles (herpes zoster) occurs when the varicella-zoster virus — which remains in the body after childhood chickenpox — becomes active again later in life. The risk increases with age and may cause a painful rash and, for some, long-lasting nerve pain or other complications requiring medical attention. Some research suggests that shingles may be associated with an increased risk of heart attack, stroke or brain hemorrhage, and possibly also an increased risk of developing dementia. Several studies also suggest that the shingles vaccine may reduce these risks, but large, well-designed studies are needed to determine this with certainty. Vaccination is the most effective way to prevent shingles. Shingrix® is approved in Denmark and provides strong protection against the disease. The DAN-ZOSTER study will examine whether vaccination — in addition to preventing shingles — may also reduce the risk of serious cardiovascular events and dementia in people aged 65 years and above.

Who can participate in the study?

You can participate in the study if you are 65 years of age or older. You cannot participate if you have previously been diagnosed with dementia or if you are being treated with immunosuppressive medication for a chronic inflammatory rheumatic disease or if you have already received a shingles vaccine. It is a requirement for participating in the study that you understand Danish or English.

How the study works

You sign up for the DAN-ZOSTER trial here on this website by clicking the “Participate in the study here” button further down the page.

The trial takes place at all DLVS vaccination clinics across Denmark. If you choose to take part, you will be randomly assigned to one of two groups:

  1. The vaccination group, who will receive the Shingrix® vaccine, and
  2. The control group, who will not receive a vaccine as part of the trial.

 

The vaccine is given in two doses, 2–6 months apart. Therefore, when you sign up, you must book two appointments at the same time so that the full vaccination schedule is planned from the beginning. Only half of participants will receive the vaccine, but both appointments must be reserved before randomisation.

Once you have clicked “Participate in the study here” further down this page and booked your two appointments, you can give consent to participate in one of two ways:

  1. Online: You give electronic consent immediately. Randomisation happens right afterwards, and you will be informed straight away whether you have been assigned to the vaccination group or the control group.
  2. Consent in person at the clinic: You book your two appointments but wait to give consent until you attend the clinic for the first time. Here you will receive oral information and provide consent, after which randomisation takes place on site. If you are assigned to the vaccination group, you can receive your first dose at this same visit. If you are assigned to the control group, no vaccines will be given. (Please note: Two appointments must be booked through this website before it is possible to attend the clinic and give consent. It is not possible to turn up and give consent without having booked two appointments through this website.)

 

If you have questions, you can find answers at the bottom of the page under “Questions and answers.” You are also welcome to call us on 88 30 01 02 on weekdays between 9:00 a.m. and 3:00 p.m.

I confirm that I have read the participant information and watched the information video

Questions and answers:

The trial is open and you can sign up, book appointments, and if you wish, provide consent already now.

You can participate in the study no matter where you live in Denmark. The shingles vaccination will be given at all DLVS vaccination centres across the country. You can choose the vaccination centre closest to you when booking your appointment.

You sign up by registering as a participant here on our website. Once your registration has been received, you can book appointments for the study visits at a location close to you. After booking, you will have the option to sign the consent form electronically from home. If you choose to do so, the randomisation—deciding whether you will receive the shingles vaccine or not—will take place immediately. Only those assigned to the vaccination group need to attend their study visits.

It is also possible to book appointments and then provide consent in person at the clinic. In that case, the randomisation will be carried out during the study visit.

Yes. Participation in the study is entirely voluntary. You can cancel your appointment at any time if you no longer wish to take part.

Because this is a randomized study, about half of those who sign up will receive a shingles vaccine (Shingrix®) free of charge. Participation is therefore an opportunity to contribute to important knowledge that can help evaluate the vaccine.

Since DAN-ZOSTER is a randomized study, about half of the participants will receive the Shingrix® vaccine, while the other half will be placed in the control group and will not receive the vaccine as part of the study.

A control group is essential for comparing vaccination with no vaccination. It allows researchers to examine whether vaccination against shingles may influence the risk of conditions such as heart attack, stroke, bleeding in the brain, other cardiovascular events, and dementia, as well as to assess the safety profile of the vaccine in a scientifically sound way.

If you are assigned to the control group, you still contribute important information to the study, even though you do not receive the vaccine as part of the research.

If you are assigned to the vaccination group, you will receive the Shingrix® vaccine at one of our clinics. After each vaccination, you will be observed briefly in case you feel unwell due to the vaccine. If this happens, our healthcare staff will be ready to assist you.

All follow-up will be conducted through nationwide Danish health registries and by accessing information in your electronic medical record. When the study has been completed, you will be able to find information about the results at the following link: https://minvaccination.dk/forskning/resultater

Because this is a randomized study, approximately half of those who enroll will be assigned to the control group, which will not receive the Shingrix® vaccine as part of the study. Having a control group is essential, as it allows us to compare Shingrix® vaccination with no vaccination — both in terms of possible effects on cardiovascular disease and dementia, and in relation to side effects. If you are assigned to the control group, you still contribute important knowledge to the study, even though you do not receive the vaccine.

If you provide electronic consent from home, you will immediately be informed whether you have been assigned to the vaccination group or the control group. If you are assigned to the control group, you do not need to attend any study visits, and no further action is required from you.

If you are assigned to the control group during the randomisation (meaning you will not receive the Shingrix® vaccine as part of the study), you still have the option to be vaccinated outside the study if you wish. Your participation in the control group does not limit your ability to receive the Shingrix® vaccine in any other way.

We expect to recruit approximately 162,000 participants for the study.

You can still take part in the trial even if you have previously had shingles. It is possible to get shingles more than once, and even if you have previously had an outbreak, you can develop it again. The shingles vaccine reduces the risk of a new outbreak in people who have previously had shingles.

You can cancel your appointment at any time and without giving a reason. To do so, simply call us at 88 30 01 02.

Shingles is caused by reactivation of a virus that can lead to a painful rash and long-lasting nerve pain, and it affects older adults more frequently. Recent research suggests that shingles may also be linked to an increased risk of heart attacks, bleeding in the brain, and dementia. Shingrix® is an approved vaccine that effectively prevents shingles. Some studies also suggest that the vaccine may reduce the risk of cardiovascular disease and dementia, but this is far from certain.

The purpose of the DAN-ZOSTER study is therefore to investigate whether vaccination with Shingrix® in people aged 65 years and older can reduce the risk of these serious health outcomes.

The study will take place at the clinics of Danske Lægers Vaccinations Service (DLVS) and is organised by the research unit at the Department of Cardiology, Herlev and Gentofte Hospital. The pharmaceutical company GlaxoSmithKline (GSK) has donated the Shingrix® vaccines and funded other expenses related to the study. GSK is a co-sponsor of the trial, which in this study means that GSK has contributed to the development of the study protocol, and that in the event of side effects, these are reported to the manufacturer of the vaccine (GSK).

 DLVS is a private company and may have a financial interest in the trial.

Vaccination can lead to both benefits and side effects. Most side effects after Shingrix® are mild and temporary, while serious side effects are rare. The most common side effects include redness, swelling and tenderness at the injection site, fatigue, headache, muscle pain, fever, chills, nausea, vomiting or diarrhoea. More serious reactions occur infrequently, and very serious side effects are very rare.

Shingrix® is an approved vaccine and is already used in Denmark and abroad to prevent shingles.

If you feel unwell after receiving the vaccine, the healthcare staff at our clinics are ready to assist you. If any complications arise afterwards, the principal investigator will ensure that you receive the appropriate medical attention.

We encourage all participants to read the leaflet “Your rights as a research participant in clinical trials involving medicines”, which has been prepared by the National Committee on Health Research Ethics, as well as the participant information document.

You do not receive payment for participating, and we do not offer any discount for taking part in the study. If you are assigned to the vaccination group, you will receive the shingles vaccine free of charge as part of the study. Participation in the study is completely free.

The shingles vaccine is approved by the European Medicines Agency to prevent shingles (herpes zoster) and long-lasting pain after shingles (postherpetic neuralgia). It can be given to adults aged 50 and older, as well as to adults aged 18 and older who have an increased risk of developing shingles.

In Denmark, the vaccine is reimbursed for people aged 50 and older who are being treated with immunosuppressive medication for a chronic inflammatory rheumatic disease. For everyone else, the vaccine is available at their own cost. Participation in this study is free of charge.

To understand participants’ health conditions, relevant registry data will be collected for up to 10 years before the start of the study and up to the day of the study visit. During the study, additional health information will be collected to monitor the vaccine’s effectiveness and safety.

The data collected may include: Diagnosis codes, Viral test results, Previous vaccinations, Hospital admissions, Deaths. Medical contacts. Registry data will be collected for all participants, including those in the control group.

Confirmation required

The target group for DAN-ZOSTER is individuals aged 65 years or older who have not already been vaccinated against shingles, have not been diagnosed with dementia, and do not have a chronic inflammatory rheumatic disease treated with immunosuppressive medication.

To continue, please confirm the following:
 
  1. That you can understand spoken and written Danish or English
  2. That you have not been diagnosed with dementia
  3. That you have not previously been vaccinated against shingles
  4. That you do not have a chronic inflammatory rheumatic disease (e.g. rheumatoid arthritis) that is treated with immunosuppressive medication. If you only take pain-relieving medication (e.g. paracetamol or ibuprofen), this does not apply to you

I confirm all of the above