An MRI Study on Muscular Diseases -Pompe Disease and Dystrophia Myotonica-
- Conditions
- Glycogen Storage Disease Type 2Dystrophia Myotonica
- Registration Number
- NCT02708784
- Lead Sponsor
- University of Aarhus
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 60
- Diagnosed Pompe disease patients, whether they are in treatment with ERT or not, or Diagnosed Dystrophia Myotonica patients.
- Healthy controls, have to be sex and age-matched to patients with muscular disease.
- Age under 18 years.
- The subjects must be able to perform an MR-scanning. Moreover they have to sign and respect the MR security rules "Kontrol skema før MR undersøgelse" and "Patient information i forbindelse med MR scanning".
- The subjects must be capable of performing the muscle strength test by the Dynamometer.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Muscle strength in Newton*meter one year Muscle strength in measured by dynamometry, and the used outcome is the "peak torque".
Muscle to fat ratio one year Calculated from the MR-images, is a measure for muscle quality. The calculations are based on the signal intensity of the fat and water Dixon MR-images.
Volume ratio one year Defined from the MR-images, is a measure for muscle quality.
- Secondary Outcome Measures
Name Time Method Forced Vital Function on year Only for Pompe disease participants
6 minutes walking test one year Only for Pompe disease participants
Trial Locations
- Locations (2)
Department of Neurology, Aarhus University Hospital
🇩🇰Aarhus C, Denmark
MR centre, Skejby University Hospital.
🇩🇰Aarhus N, Denmark