Q: What’s the difference between screening and the trial?
A: The screening test will find out who is at risk of diabetes. The trial will find out whether the medication prevents diabetes. adAPT will only give the trial medication to children who are at risk of diabetes.
Q: What does screening involve?
A: The blood test for diabetes antibodies is made generally pain-free after using an anaesthetic cream or spray. The more antibodies found, the greater the risk of diabetes. We will be inviting children who have two antibodies or more to join the trial.
Q: Does a negative result mean no diabetes in the future?
A: The risk where no antibodies are found is very low, and certainly no greater than for an average member of the public. Although childhood diabetes is increasing rapidly, it is still a rare disease.
Q: What is the risk of diabetes to my child if only one antibody is positive in the screening test?
A: Every child has some risk of diabetes, but one antibody does not signal a big enough risk of diabetes. Only when there are two antibodies or more does the risk begin to rise. Families will be given a ‘positive’ (two or more antibodies) or ‘negative’ (fewer than two antibodies) are found in the screening test result.
Q: A little bit of knowledge may not be not be a good thing. If you find that your child has these antibodies, what can they do about it? As a parent you would say to yourself ‘OK, but what next?’
A: Understood. The aim of the trial is to prevent the onset of diabetes in those with antibodies – there is nothing else available at present. A successful trial could mean the first ever treatment to prevent childhood diabetes.
Q: Are these antibodies specific to diabetes, or can they relate to anything else?
A: The antibodies that adAPT will test are specific to diabetes.
Q: Can the blood test for antibodies be done by the GP, rather than join a trial?
A: No. Although its a reliable test, it is not used routinely because (at the moment) there is no treatment to offer if it were found to be positive. We hope that this will change once a successful treatment for preventing childhood diabetes has been found.
Q: What are the implications of a positive screening result for employment/insurance?
A: None. Insurance companies are not (currently) permitted to seek information on biomarkers such as the antibodies in the absence of disease. If this changes we will advise families who are taking part in the trial.
Q: What is a randomised controlled trial (RCT)?
A: RCTs are the gold-standard by which doctors and researchers scientifically test the effectiveness of a treatment or medicine. All prescription drugs have been subjected to one or more RCT’s to show that they are safe, and that they work.
Q: Why does it take 15 years for a new idea to get tested in a clinical trial?
A: There are many factors. Most importantly, doctors question new ideas that challenge established teaching, and need good reason to think of exploring alternatives. It also takes time to attract the funding, (RCTs can cost millions of pounds) design and write the protocol and study documents, obtain approvals from the safety and ethical committees, and set up the study sites around the country.
Q: What is meant by double-blind?
A: In an RCT neither the participants nor the research teams know who is taking the active treatment. A computer will be used to randomly allocate the participants into two groups. One group will be given the medication, and the other group a look-alike (dummy or placebo). The placebo is inactive, and nobody (only the computer) knows who’s getting what (although the research doctor can find out if this information is needed in an emergency). This approach is crucial because it means that no-one and nothing, except the trial medication, can influence the result. The outcome of the trial is known only once the allocation is decoded.
Q: Can I choose which treatment group my child joins?
A: No. In a ‘double-blind’ trial neither the participant, their family nor the doctors conducting the trial know who is receiving the active and the inactive medication. This way, it should not be possible to influence the result. Be reassured however, that the trial families will know the results before the general public, and will have access to the trial medication if the trial proves successful.
Q: What’s special about adAPT?
A: This trial is different because it proposes a fundamentally different mechanism for childhood diabetes. The mechanism may explain the sharp rise in diabetes over recent years, and adAPT will be testing it for the first time.
Q: If it doesn’t work, will the trial have been a waste of time?
A: No. Doctors will have learned a lot about diabetes, and may conclude that the new mechanism proposed is not right. Negative information can be valuable.
Q: Why should my family join adAPT?
A: We think there are two good reasons. First, the screening test will tell whether children with a brother, sister or parent with diabetes carry a similar risk to someone in the general population. Nineteen out of every 20 children screened will show no greater risk than the general population, which will be reassuring to everyone. Second, the one in 20 children screened who is at increased risk of diabetes will have the opportunity to join a trial designed to investigate a treatment that may reduce diabetes at a time when there is no other treatment available.
Q: I know there was a study where doctors gave small amounts of insulin by mouth or by injection to rest the beta cells. What is the difference between giving insulin by mouth or by injections and adAPT?
A: The trial using small amounts of insulin (DPT-1) didn’t work. Both injectable insulin and oral insulin were used in the hope that small amounts might stop the autoimmune attack thought to be responsible. adAPT is designed to reduce the demand on stressed insulin cells – a different concept.
Q: Would you continue to measure antibody levels throughout the trial?
A: Yes. A fall in the antibody levels may indicate early improvement.
Q: How long should you expect to be on the study medication?
A: Up to five years, as this would allow us to see if the treatment worked.
Q: There are no guarantees for any drug and I would have concerns taking part after my other child who has diabetes was unwell.
A: The study medication is known to be safe in children, and there are no reports of children being very ill when taking it. The Medicines and Healthcare Regulatory Authority(MHRA) and National Research Ethics Committee(REC) who are responsible for the review of medical research proposals have approved adAPT.
Q: How does the study medication work, and how is it different?
A: It reduces the demand on insulin cells, and this reduces the inflammation that stresses them. We believe that a small effect will have a big benefit. The medication works quite differently from the immune therapies that have been used to test the autoimmunity theory for type 1 diabetes.
Q: How would you describe the study drug ?
A: A fruit-flavoured liquid that will be given by oral syringe so that the dose can be adjusted as the child grows. It has a bitter taste which may be more pleasant when the medicine is stored in the fridge.
Q: If successful, this study will help other antibody-positive children likely to develop diabetes in the next five years, but will it help people in their 20’s and beyond?
A: Yes, it will provide a means of preventing type 1 diabetes in antibody positive people of all ages.
Q: When do children start to lose insulin cells?
A: We all lose beta cells, this starts when we are born, but usually the reserve is sufficient to last a lifetime. Inflammation speeds up beta cell loss, and the trial is trying to slow the loss by reducing the inflammation that accelerates it.
Q: When does the study analysis start?
A: At the end of Stage 1 (around two years after the first child is screened).
Q: How many children are there in Scotland with type 1 diabetes?
A: In 2014, the Scottish Study Group (SSG) counted more than 6,000 families in Scotland where a member under the age of 25 had type 1 diabetes.
Q: Would you consider going into schools for the study tests (given the number of visits required)?
A: No. The tests need the supervision and facilities that can only be found in a hospital clinic.
Q: A positive result may raise anxiety levels. My children have never considered they might become diabetic, and it may cause them to worry about it.
A: Understood, although many children tend not to worry about these things. The trial may provide a means of preventing diabetes.