Lay Statement
132nd ENMC International Workshop
Planning
steroid dosage trials in Duchenne muscular dystrophy
3rd-5th January 2005
Twenty-six
participants from Belgium, Canada, France, Italy, the
Netherlands, Sweden, the UK and the USA met in Naarden,
the Netherlands, on 3rd-5th January under the auspices
of the European Neuromuscular Centre Clinical trials
unit. The participants at the meeting comprised the
steering committee of the ENMC/ Muscle Study Group on
development of trials in DMD and members of various
working groups involved in developing aspects of the
trial protocol. The meeting was a follow up of the 124th
ENMC workshop held in April 2004 at which the initial
plans to establish a trial of corticosteroid dosage
regimes in DMD were made, and following which patient
information material on the use of steroids in DMD was
generated (http://www.enmc.org/workshops/reports.cfm?p=157).
Plans to submit
an application for a planning grant to implement a
randomised controlled trial of corticosteroid dosage
regimes are well advanced. Investigators from 14
countries have expressed an interest in joining the
trial. The basic protocol was discussed. As the
unresolved clinical question is about the relative
benefits and side effects of different steroid dosage
regimes over the long term, it was decided to test four
regimes (0.75mg/kg/day prednisone, 0.9mg/kg/day
deflazacort/ 0.75mg/kg/day prednisone 10 days on and 10
days off and 0.5mg/kg/day prednisone) over a three year
period initially with the intention to have in total a
10 year period of follow up. Children with a confirmed
diagnosis of DMD around the age of diagnosis or shortly
thereafter (4 to 7 years old) will be recruited and
randomised to one of the four arms of the trial. In
order to ensure a high degree of clinical relevance a
primary outcome measure related to muscle function (the
ability or time to get up from a lying position) was
chosen as a surrogate for the functional milestone of
ultimate interest: the loss of ability to walk
independently, which will be the primary outcome measure
for the longer follow up period. Other functional
outcomes including respiratory function will also be
measured. Side effects will be monitored and managed
essentially according to the table presented in the last
workshop report, and working groups will generate
standardised information for other areas of management
including physiotherapy support, dietetic advice, advice
on the management of behavioural problems, etc. which
will be made available through the ENMC website.
Three areas
were addressed in more detail. The first relates to
issues of health services research: quality of life,
health economics and caregiver burden. This trial
provides a unique opportunity to collect data on these
areas across a broad group of children, and choice of
the most relevant instruments is the focus of a working
group led by Michael Rose. The second area, of bone
protection, is led by Doug Biggar and Roz Quinlivan. As
the effects of steroid use on bone health is an area of
major concern, a protocol is under development to
monitor this carefully during the trial. Finally, John
Bourke is leading a group to study the effects of the
steroid regimes on cardiac function. All of these
discussions will continue after the workshop through
electronic forums hosted by the ENMC.
It is important
to note that because of the scale and of complexity of
the planned trial, this will not start for at least
another 18 months. It is not appropriate for treatment
with one of the proposed steroids regimens to be
withheld from DMD patients in the meantime.
The workshop
was organised and chaired by Kate Bushby (Newcastle upon
Tyne, UK) and Robert Griggs (Rochester, NY, USA). Other
participants were Anna Ambrosini (Milan, Italy), Anne
d'Andon (Paris, France), Corrado Angelini (Padua, Italy),
Maria Luisa Bianchi (Milan, Italy), Doug Biggar
(Toronto, Canada), John Bourke (Newcastle upon Tyne,
UK), Gunnar Buyse (Leuven, Belgium), Emma Ciafaloni
(Rochester, NY, USA), Michael Davie (Oswestry, UK),
Michelle Eagle (Newcastle upon Tyne, UK), Imelda de
Groot (Huizen, The Netherlands), Mike Haddaway (Oswestry,
UK), Elaine McColl (Newcastle upon Tyne, UK), Mike
McDermott (Rochester, NY, USA), Jerry Mendell (Columbus,
OH, USA), Phil Miller (St. Louis, USA), Lucia Morandi
(Milan, Italy), Francesco Muntoni (London, UK), Giovanni
Nigro (Naples, Italy), Shree Pandya (Rochester, NY,
USA), Roz Quinlivan (Oswestry, UK), Michael Rose
(London, UK), Thomas Sejersen (Stockholm, Sweden),
Adrian Trenholme (New Zealand), Elizabeth Vroom
(Amsterdam, The Netherlands)