Frequently Asked Questions (FAQs) about this study:
What is the aim of the FOR-DMD study?
The FOR DMD study will look at the benefits and side effects of the three most widely prescribed steroid treatments for Duchenne muscular dystrophy (DMD). The type of steroids commonly prescribed for DMD are called corticosteroids. Corticosteroids are a type of drugs similar to natural hormones produced by the adrenal glands. They reduce inflammation and suppress the immune response. Corticosteroids are currently the only medicine that might stabilise or even increase muscle strength in DMD boys over a limited period of time, although the response and benefits may vary from boy to boy. The main corticosteroids that are used in DMD are Prednisone (or Prednisolone) and Deflazacort. These are not “anabolic steroids” (or “glucocorticoids”) which are what athletes use illegally to build up muscle – these do not have an effect in Duchenne muscular dystrophy.
We will compare three different treatment groups:
- Daily prednisone
- Daily deflazacort
- Intermittent prednisone (10 days on alternating with 10 days off).
The study is randomised (your child’s treatment group will be decided randomly, as in drawing names from a hat or tossing a coin) and double-blind which means that neither participants nor their doctors will know which group the boy is in (though the doctor can find out if necessary, such as in a medical emergency).
All three steroid treatments are commonly used in boys with DMD and are known to be beneficial. Benefits include an increase in the length of time that boys could continue to walk, reduction in the development of curvature of the spine, a longer time of adequate breathing, and possibly protection against the development of heart problems. However we do not yet know which of the three treatments has the most benefit and most tolerable side effects. Therefore, this is a trial of present day steroid use which is needed because the practice of prescribing steroids currently varies a lot between doctors. This means that patients may not receive the best possible treatment and management of side effects. In this study, all study participants will be receiving treatment with steroids and will be managed in line with the recognized standards of care.
Who is eligible to be in this study?
To be in this study your child must have a confirmed diagnosis of DMD by genetic test showing a mutation (deletion, duplication or point-mutation) in the dystrophin gene. He must be aged between 4 and 7 years old and have not previously been treated with oral steroids (eg tablets or liquid solution). Previous or current treatment with steroids by inhaler (eg for asthma) or as an ointment (eg for eczema) would not preclude your child from taking part in the study.
Where will this study take place?
This study will take place in at least 40 muscle centres in the US, Canada, UK, Germany and Italy; other countries may also be included later. A list of sites that will be taking part in the study will be available soon. The lead investigators are Prof R Griggs at Rochester NY (US) and Prof K Bushby at Newcastle University (UK).
What will happen during the study?
If you are interested in the study please discuss it with your doctor locally. Your doctor will direct you to your nearest recruiting site. If your child appears to be eligible, he will be invited to visit the study site for a screening visit. At this appointment the study will be explained to you and your child in detail and, with your consent, some tests will be performed to ensure your child meets all the necessary requirements to participate in this study. If these tests confirm that your child is suitable for the study, you will be asked to visit the study site again and your child will be given the study drug. After this visit, you and your boy will visit the study site 3 and 6 months later and then every 6 months after that. There will be a total of around 8-13 visits depending on when your child is enrolled in the study. At each visit, your child will be assessed to monitor benefits and side effects of corticosteroids.
We expect your child will be in the study for between three and five years. We hope that participants will be able to find a muscle clinic that is taking part in the study reasonably close to where they live and that the study visits will be part of their routine follow up.
Is there any funding to help pay for travel?
No – after the screening visits, the frequency of clinic / hospital visits should not be any more than is usual for follow up in DMD
Will I or my boy get paid for participating in this study?
Will I have access to the drug/treatment once the study has ended?
Yes, your doctor will discuss treatment options at the end of the study to decide the best steroid treatment plan for your child.
Both Prednisolone and Deflazacort are available on prescription in Europe. Deflazacort is currently not available in US and we have had discussion with the American Regulatory Authorities to see if it could become available if the study showed it to be better than the other treatments.
Will participating in this study prevent my child from taking part in other clinical trials?
We are aware that trials of other potential new therapies may start during the course of the study. As steroid treatment is part of the normal standard of care in DMD we do not believe that being in this study would prevent your child from being in another study later if there was one that he was eligible for. We hope that the majority of participants will finish the whole trial, however as with any clinical study you are entitled to withdraw your child from this study at any time if you no longer wish your child to take part.
What are the allowed visit windows?
The allowable windows are ± 14 days for visits at months 3 and 6 (T3 and T6) and ± 30 days for all subsequent (6 monthly) visits. For phone calls the window is (+/- 7 days) during the first 6 months following the baseline visit, then (+/- 14 days) for subsequent calls.
All visit dates and windows are calculated from the ACTUAL baseline visit date (not the target baseline visit date on CRF01). Therefore subsequent visit target dates remain based on the actual baseline date, regardless of whether some previous visits have occurred early or late.
If visits occur out with these windows, this will represent a protocol deviation and therefore should be avoided if at all possible; persistent deviations may constitute a serious breach of protocol, requiring notification to regulatory and ethical authorities.
Do screening procedures need to be repeated if the boy had them recently performed as part of his standard of care?
This should be discussed with the Chief Medical Monitor (Dr Michela Guglieri) on a case by case basis. Procedures will not usually need to be repeated if they have been performed within 90 days of baseline. Please note that if a procedure was performed as part of the subject’s standard care, the PI should confirm that the procedure was performed under the same criteria required by the study protocol and that all requested parameters have been collected and reported, in order to complete the appropriate eCRF.
Does Ulna Length need to be measured and documented for all subjects (inclusive of those that can stand straight) at each visit?
No, ulna length does not need to be measured in boys who are able to stand straight. It will be measured (together with height) only when the boy stands on his tiptoes (and is unable to put the heels down) and it will become the sole, indirect, measure of height when the boy is not able to stand any longer.
Should the “musculoskeletal” section of the physical examination be completed as normal (since it is normal for DMD) or as abnormal (since it is abnormal for someone without DMD?)
If a subject shows signs of DMD as expected for a boy of his age with this condition, the musculoskeletal section of the physical examination should be completed as “abnormal” – comment: DMD – non clinically significant .
No details of the DMD clinical signs should be reported on eCRF 21 as these will be recorded as part of the subject medical history.
Changes from baseline which are compatible with natural course of DMD should not be recorded. However, any clinical signs (or changes when compared to baseline) of DMD which are unexpected (e.g. more severe than expected for subject age) should be recorded. Any worsening should be reported as Adverse Event (CRF30).
Will families be provided with a diary to document Adverse Events, concomitant medications and any other / problems?
No. Although we appreciate that this would be very useful, diaries are not provided as part of the FOR DMD study. Please also note that anything we distribute to the subject must be approved by the relevant Research Ethics Committee/Institutional Review Board. If your clinic typically provides some sort of diary for boys on steroids regardless of trial participation, that is acceptable (i.e. it is considered “standard practice”). Otherwise, families can be encouraged to report events on their own calendars or diaries and bring these to clinic where study staff can report the events on the study worksheet and eCRF.
Can the eye check be performed by a subject local optician or do the boys need to be seen by a specialist at the hospital?
The eye check can be performed by any qualified eye care practitioners and is not required to be carried out by an Ophthalmologist at the hospital. However, the person performing the test must be aware of the study requirements and the specific clinical question as reported in eCRF 26. A written report of the assessment is required as source data.
BIOBANK and BONE DMD
Have sites been provided with Tubes and vials for Biobanking?
No. Sites should use their own tubes and vials for Biobanking samples. Please contact us if you have any issues with this. Sites have been provided with vials for BONE DMD urine and blood samples only.
Should Biobanking and BONE DMD samples be sent centrally right after collection?
No. Biobank and BONE DMD samples only need to be sent centrally once a year. Sites will be contacted by us when shipment is due with details for shipment arrangement. Cost for shipments will be covered by FOR DMD. Please note, Biobank and BONE DMD samples will be delivered to two different centres (in two different countries) and therefore samples cannot be packed together!
Biobank samples only need to be sent to the Newcastle BioBank (UK) once a year. Cost for shipments will be covered by FOR DMD, however sites are required to provide their own dry ice. Sites should contact us if they anticipate any issue with this.
BONE DMD urine and blood sample will be shipped to Maria Luisa Bianchi in Italy as soon as baseline samples have been collected from 2-3 subjects at the site (and approximately 6 months after first baseline visit at the site) and annually thereafter. Cost of shipment via courier will be covered by Maria Luisa Bianchi and dry ice will be provided by the courier.
Why should I consider participating in this study?
While no personal benefit to participants can ever be guaranteed from being in a clinical trial, there are other benefits, including
- Allowing you to play an active role in the DMD research
- Access to medical specialists that might not normally be available to your boy
- Access to high standard medical care and management in DMD
- Contributing to the better understanding of DMD and what the best steroid treatment is
All participants will be getting active drug (there is no placebo group) and will be followed up and managed during the trial according to current standards of care.
What should I do if I decide I want to take part in this study?
We hope for recruitment to start in the Autumn of 2012. Further information on how to contact sites will be available in the near future, but if you are interested, speak to your doctor or local muscle specialist to see if they are planning on taking part or they have more information and contact details of sites who are taking part.
Who is funding this study?
This study is funded by the US National Institutes of Health(NIH)National Institute of Neurological Disorders and Stroke (NINDS)
Where can I learn more about this study?
You can learn more about this study at www.DuchenneConnect.org, www.muscular-dystrophy.org and www.for-dmd.org. It will be listed on www.clinicaltrials.gov nearer the recruitment start date.