Glycogen Storage Disease Type 2 Clinical Trial
Official title:
Function, Structure and Quality of Striated Muscles in Patients With Muscular Diseases - an MRI Study on Pompe Disease and Dystrophia Myotonica
The aim of the project is to develop new Magnetic Resonance (MR) imaging techniques for
better diagnosis and monitoring of patients with muscular disorders.
Muscle quality in patients with Late Onset Pompe Disease (Acid Maltase Deficiency type 2)
and in patients with Myotonica Dystrophy will be evaluated, by determining muscle strength
in relation to muscle size and muscle strength in relations to fat-muscle ratio.
The investigators focus on the rare Glycogen Storage Disease type 2 (Pompe Disease), a
genetic disease characterized by gradual replacement of muscular tissue with glycogen and
fat, resulting in loss of muscle mass and muscle strength. Pompe disease is of particular
interest since a new drug has recently been developed and approved for this, hitherto
untreatable, condition. This treatment is expensive, and it is therefore of great importance
to have objective methods of examination to monitor the disease and the effects of the
treatment.
Until now, monitoring has been based primarily on physical test such as the 6 min walking
test and isokinetic dynamometry. These methods may not be sensitive enough to detect changes
for shorter periods in slowly progressing-diseases. New MRI techniques may be useful for
monitoring in myopathies.
The other disease the investigators are focusing on is Myotonic Dystrophy, because of its
great similarities with Pompe Disease. As with Pompe disease, the muscular tissue slowly
degenerate and fat infiltrations occur.
Hypothesis
In this study, the investigators want to test the following hypotheses:
- Intrinsic muscle strength in patients with Pompe disease and Myotonic Dystrophy is
linear correlated with muscle to fat volume ratios from MR images.
- Disease grade in patients with Pompe disease and Myotonic Dystrophy corresponds to the
extent of fat proliferation in the muscles of the lower extremities.
- Intrinsic muscle strength is a more specific and sensitive method to reveal the effects
of enzyme replacement treatment in patients with Pompe than the 6 minutes-walking-test.
Methods Fifteen patients with LOPD from Denmark and from Germany (Münster), 15 patients with
Myotonic Dystrophy and 30 controls are included.
The MR protocol includes the special T1 weighted sequence DIXON (1x1x3mm3; TR: 5.31ms TE:
2.46ms) enabling acquisition of muscle and fat images at 3 Tesla (Magnetom-Skyra, Siemens
AG, Erlangen, Germany). The MR scans will consist of 400 axial slices covering from L1 to
the ankle resulting in a total scan time of 22½ minutes.
Muscle strength will be measured by isokinetic dynamometry. The measurement will be done
using the Biodex System 3 PRO Dynamometer (Biodex Medical Systems Inc. NY, USA) for which a
standardized protocol has been developed.
Maximal isokinetic strength of extensors and flexors of the dominating arm and extensor and
flexors at the knee, ankle and hip of the non-dominant lower extremity will be measured.
There are no known side effects related to MR-scanning. During the examination, the subjects
will wear headphones in order to reduce the high sounds that come from the scanning machine.
The scan is painless and there is no use of contrast. The only disadvantage is that the
person has to lie motionless for 20-30 minutes. There are some security rules to respect in
order to avoid accidents due to metals being attracted by the machine's strong magnetic
field.
No side effects are associated to muscle strength measurement with the Dynamometer.
However, weak patients may be a bit tired after the examination, as they have to perform
some movements using all their force.
Statistics Comparison between baseline and visits will be performed using conventional
statistic methods as unpaired t-test or non-parametric tests such as Wilcoxon signed-rank
test. In variation analyses of several groups ANOVA and ANCOVA will be used. A significant
difference of p-values below 0.05 has to be determined, to determine the validity of the
findings. With a significant level of 5% a power calculation estimated a needed sample size
of 14 patients, with a power of 90%. The calculation is based on an expected decrease in
muscle volume compared to fat (1.2 vs 0.95 with a standard deviation of 0.2). The power
calculation is an estimate, but compared to a similar studyxiii the sample size includes an
extra 3 subjects. Given the rare condition of PD, inclusion of patients will continue even
if the required minimum is not achieved.
The same statistics calculation will be used for patients with Dystrophia Myotonica, who are
included in the study because of its great similarities with Pompe Disease.
Perspectives If MRI imaging is a sensitive method with high specificity for the assessment
of muscle quality in myopathies, this technique may be used for diagnosis and continuous
validation of the proper treatment of patients with Pompe disease and with related muscular
diseases.
Clinical trial: Day one. Patients with Pompe Disease and Dystrophia Myotonica The patients
will come to the neurological department of Aarhus University Hospital at Nørrebrogade.
Their muscle-strength will be measured by the Dynamometer; these measurements will take
approximately 2 hours.
In addition, Pompe patients will undergo the 6 min walking test, the vital capacity and
negative inspiration/expiration tests, the sit-to-stand test as well as a structured
neurological examination. This will take about 1 hour.
After the first part of the examinations, the patients will be driven, by the hospital
minibus, to the MR center at Skejby University Hospital, where the MR-scanning will be done.
The total timeframe for the scanning, included change of clothes, information and scanning,
will take 1,5 hours. In case that it´s not possible to make the physical examinations and
the scanning on the same day, the scanning will take place another day, within the following
7 working days.
Healthy controls The control subjects will be received at the neurological department of
Aarhus University Hospital at Nørrebrogade. Their muscle-strength will be measured by the
Dynamometer; the measurements will take approximately 2 hours. Afterwards, they will be
driven, by the hospital minibus, to the MR center at Skejby University Hospital, where the
MR-scanning will be performed. The total time for the scanning, included changes of clothes,
information and scanning, will take 1,5 hours. In case that it´s not possible to perform
both the physical examinations and the scanning on the same day, the scanning will take
place another day, within the following 7 working days.
Clinical trial: day 2 After 8 months, patients with Pompe disease will come for new
investigations. The same examinations, as described above, will be performed.
;
Time Perspective: Cross-Sectional
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N/A |