An MRI Study on Muscular Diseases -Pompe Disease and Dystrophia Myotonica-

March 9, 2016 updated by: University of Aarhus

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.

Study Overview

Status

Unknown

Conditions

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.

Study Type

Observational

Enrollment (Anticipated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Aarhus C, Denmark, 8000
        • Department of Neurology, Aarhus University Hospital
      • Aarhus N, Denmark, 8200
        • MR centre, Skejby University Hospital.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients will be recruited trough their attendance to the Hospital. Pompe disease patients will be recruited from all the treating hospitals in Denmark and from the University hospital of Münster. Patients with Myotonic Dystrophy will be recruited trough their attendance at Aarhus University Hospital.

Healthy controls will be recruited from the general Danish population.

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Pompe disease
Patients will perform muscle strength measurement with dynamometer and MR-imaging. After 8 months the investigations will be repeated.
Myotonic Dystrophy
Patients will perform muscle strength measurement with dynamometer and MR-imaging. The investigations will not be repeated after 8 months.
Healthy controls
Patients will perform muscle strength measurement with dynamometer and MR-imaging. The investigations will not be repeated after 8 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle strength in Newton*meter
Time Frame: one year
Muscle strength in measured by dynamometry, and the used outcome is the "peak torque".
one year
Muscle to fat ratio
Time Frame: 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.
one year
Volume ratio
Time Frame: one year
Defined from the MR-images, is a measure for muscle quality.
one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6 minutes walking test
Time Frame: one year
Only for Pompe disease participants
one year
Forced Vital Function
Time Frame: on year
Only for Pompe disease participants
on year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Aarhus

Investigators

  • Study Chair: Henning Andersen, Professor, Aarhus University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2015

Primary Completion (Anticipated)

August 1, 2016

Study Completion (Anticipated)

September 1, 2016

Study Registration Dates

First Submitted

December 8, 2015

First Submitted That Met QC Criteria

March 9, 2016

First Posted (Estimate)

March 15, 2016

Study Record Updates

Last Update Posted (Estimate)

March 15, 2016

Last Update Submitted That Met QC Criteria

March 9, 2016

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PsDM15RMBH

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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