Frequently Asked Questions

Click on the questions below to see the answers.

What is a clinical outcome study?

A clinical outcome study evaluates the results from a variety of tests in a group of people with a specific disease over a period of time. This type of study allows us to determine which tests are best at measuring changes that can occur in that disease. These “clinical outcomes” can then be used to assess the effectiveness of therapies during clinical trials.

What is the purpose of this clinical outcome study?

The aims of this clinical outcome study are to:

  •  Define the best tests for measuring the disease as it progresses for use in clinical trials for dysferlinopathies.
  • Collect biological samples for the identification of disease markers (indicators, signs) that will allow researchers to monitor the disease during clinical trials in a non-invasive manner.
  •  Collect accurate details about all the different forms of dysferlinopathy by measuring disease progression in a large group of people. This information will be used to help enhance patient care.
Who is taking part in this study?

Individuals wishing to take part in this study will need to have a confirmed diagnosis of LGMD2B, Miyoshi Myopathy or any other form of dysferlinopathy. This study is part of an international study involving patients from eight different countries: Australia, France, Germany, Italy, Japan, Spain, the United Kingdom and the United States of America. Relevant health information will be collected from at least 150 individuals.

How will this study benefit participants?

Participants may not personally benefit from allowing their data to be used in the study. However, it will provide important information to researchers and health professionals to help them better understand the natural history, pathogenesis and clinical outcome of LGMD2B, Miyoshi Myopathy and other dysferlinopathies, and will eventually influence the planning of future clinical trials. As this group of muscular dystrophies is very rare, we need to collect and record information from as many patients as possible. It is anticipated that evaluation of all these data across the 14 participating centers around the world will benefit patients with LGMD2B, Miyoshi Myopathy, or other forms of dysferlinopathy in the future. We believe that the development of the International Dysferlinopathy Registry, www.dysferlinregistry.org, and the information collected in the clinical outcome study will lead to a better understanding of these conditions, ensuring future optimal caring, and to the development of new and better therapies in the future. See the question "What is the International Dysferlinopathy Registry?" below for more information.

What are the risks of participation?

As this study does not involve any treatment interventions, there should be no specific risk to participants. The taking of blood samples (for standard laboratory tests or "biobanking") or skin biopsy (for "biobanking") causes no serious problems for most people, but it can cause some bleeding, bruising and/or discomfort at the injection site and may (in the case of the skin biopsy) leave a small scar. See the question "What is 'biobanking'?" below or the section on biobanking for more information.

 

The MRI/MRS scans that will be performed are commonly performed and generally safe. However, you need to be aware of the possible side effects. Some people are claustrophobic in the scanner; however, you will not be completely enclosed. The radio waves used in the MRI can cause metal and other tissues to heat up. You will therefore need to inform us if you have any of the following: surgical clips, a pacemaker or heart defibrillator, stents in the heart or arteries, an inner ear implant, a medicine infusion pump (e.g. insulin pump), a neurostimulator, a shunt in the brain, joint replacements, large metal implants, metal fragments anywhere in your body, eye, penis or breast implants, an intrauterine contraceptive device, or any body piercings. You may find that teeth fillings tingle during the scanning, but they are safe. It is also important for us to know if you have any allergies, tattoos, transdermal patches, or gun/shrapnel wounds.

What happens at each study visit?

For the clinical outcome study, participants are assessed on 6 occasions over 3 years. Each visit lasts 1 to 1 ½ days. The first visit is called the screening visit and is the visit to assess eligibility. The second visit (called the baseline visit) occurs approximately a month after the screening visit. After the baseline visit, participants are assessed again at 6 months, 12 months, 24 months and 36 months post baseline so that we can monitor disease progression. A variety of assessments are performed at each visit according to the participant’s level of ability (see below):

 

  • Medical assessment (at all 6 visits): a general physical and neurological examination (including heart and lung examination), and medical questions about symptoms, problems, medication use, etc.
  • Cardiac studies (only at baseline and 36 months): echocardiography and electrocardiography.
  • Questionnaires: quality of life & exercise questionnaires (at baseline, 12 months, 24 months, and 36 months), pregnancy questionnaire (where appropriate).
  • Physiotherapy assessment (at all 6 visits): Muscle Strength Testing (Manual Muscle Testing and Myometry), Functional/activity Testing (MFM-20, Adapted North Star Ambulatory Assessment for Dysferlin [ambulant patients only]), Brooke Upper Extremity Scale Test, Jebsen Test, Activlim Questionnaire, EK Scale [non-ambulant patients only]), and Timed Tests (ambulant patients only: timed rise from floor, 10 metre walk/run, timed up and go test, timed climb 4 steps, timed descend 4 steps, 6 minute walk test).

 

We are also collecting blood samples and performing “Magnetic Resonance” (MR) investigations:

 

  • Blood samples: at baseline visit and then annually (at 12 months, 24 months, 36 months), blood will be collected for standard laboratory tests.
  • MRI scans and MRS measurements: at baseline visit and then annually (at 12 months, 24 months, and 36 months), MRI and MRS investigations will be done to assess the overall patterns and extent of muscle damage in upper and lower limbs (MRI), and to evaluate the energy levels within your muscles and how they respond to exercise (MRS).  For more information about MRI and MRS, see the question "What are magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)?" below.


An optional part of the clinical outcome study involves the collection of biological samples for "biobanking." For more information on "biobanking," see the question "What is 'biobanking'?" below. Please note that NO muscle biopsy will be taken for this study. For more information, see the collected information section of this website.

What are magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS)?

MRI/MRS are special imaging/measurement techniques that use powerful magnets, radio waves and computers to produce detailed images (or scans) or measurements of the different tissues of the human body in a non-invasive way (without the need for a biopsy). MRI gives information about the structure of the body (the distribution of water and fat), while MRS gives biochemical information about the tissues in the body. These techniques do not use X-rays and do not cause pain or discomfort.

 

The entire scanning session (MRI and MRS) takes approximately 2-3 hours and you will need to lie on your back on a moveable table, which slides inside the cylindrically shaped scanner. The scanner is open ended and you will not be completely enclosed at any time. A radiographer will operate the scanner from behind a window, but will be able to hear and see you during the scanning. You will be given a call button to hold during the scanning, which you can press to get the radiographer’s attention, should you need assistance. Please note that there will be someone to help you on and off the table if needed. It takes several minutes for each image to be taken, and it is important to lie still and breathe gently during the process.

 

The machine is noisy and will make a loud knocking or buzzing sound throughout the scanning. However, we will provide you with ear plugs and headphones which will help block a lot of the sound out. You will be able to eat and drink as usual before the scanning and will not need to take any special precautions. The risks of MRI/MRS are explained in the question "What are the risks of participation?" above.

Where is the study being done?

The study is being conducted in 14 centers across the USA, Europe, Japan, and Australia. Click here for the complete list of locations.

Is this study testing a treatment or drug?

No, the study does not involve any treatment interventions.  However, the outcome measures identified in this study are needed for the development and success of future clinical trials. In addition, the information gained in this study will provide a better understanding of the disease, ensure optimal care and treatment, and will lead to new and better therapies.

What information is being collected and what investigations will be carried out?

For the clinical outcome study, medical, physiotherapy and MRI/MRS assessments are being performed, according to each participant's level of ability, on 6 occasions over 3 years. These assessments include:

 

  • Heart, lung and neurological examinations - all visits
  • Measurements of muscle strength/functionality - all visits
  • Echocardiography and electrocardiography - 2 visits
  • Magnetic Resonance (MRI/MRS) investigations - 4 visits
  • Questionnaires to evaluate activity/quality of life - 4 visits
  • Standard laboratory tests on blood samples - 4 visits

 

For more information about the study visits, see the collected information section of this website.

Who is participating?
  • Over 200 ambulant and non-ambulant participants age 10 and older.
  • Participants have confirmed diagnosis of dysferlinopathy proven either by the identification of two pathogenic dysferlin mutations OR one pathogenic dysferlin mutation AND documented dysferlin protein expression levels in the disease range as assessed by immunoblot on either blood or muscle protein extract
Who is collecting the information, when and how, and who will be able to see it?

A medical doctor/ specialist nurse and physiotherapist at the clinic will carry out the medical and physiotherapy assessments at each of the 6 clinic visits and collect the associated information on designated report forms. MRI/MRS scanning will be carried out by MR experts, possibly on different days that are close to the clinic visits. All the collected data will be stored in a secure database. If the participant consents blood and skin samples will also be taken for storage in the MRC Neuromuscular Centre BioBank. See the question "What is 'biobanking'?" below for more information.

What is "biobanking"?

There have been large advances in the study of human genetics in recent years, which has opened up new perspectives in the field of scientific research on diagnostic tools and treatment strategies for many different diseases. These research studies involve the study of human biological material, such as blood serum, blood plasma, DNA, RNA, fibroblasts (cultured cells) from skin, muscle tissue, etc. To enable researchers across the world to have access to quality human biological material for rare diseases, collections or "banks" were created that store biological samples donated by patients suffering from all kinds of diseases. The EuroBioBank, www.eurobiobank.org, is a European network of "banks" that store biological material from patients with rare diseases. Individuals donating biological samples for a "biobank" will not receive any financial benefit from any future treatments that may be developed from research involving their samples.

What biological samples will be collected for “biobanking” in this clinical outcome study?

Donating samples for "biobanking" involves that if you specifically consent, blood will be collected from you once a year (4 times in total) to obtain serum and plasma, some more blood will be collected only at the beginning of the study to extract DNA and RNA, and a skin biopsy will be taken only once (at the beginning of the study) to culture fibroblasts. These samples will be stored in the MRC Neuromuscular Centre BioBank (which is part of the EuroBioBank) for use in future approved research projects. The skin tissue itself will be discarded once the fibroblast cells have been grown. See the question "What is 'biobanking'?" above or the section on biobanking for more information.

Is donating "biobanking" samples required for participation in the clinical outcome study?

No, donating the blood samples and/or the skin sample for "biobanking" is not required, in the sense that you can participate in the clinical outcome study with or without donating any biological samples for "biobanking," or with donating only the blood samples or only the skin sample. Please note that choosing not to donate these samples will not affect your participation in the other parts of the clinical outcome study. See the question "What is 'biobanking'?" above or the section on biobanking for more information."

What is a skin biopsy?

A skin biopsy involves taking a small piece of skin with a little round shaped knife with a diameter of 3.5 or 4 mm. It is usually done under local anesthetic with an anesthetic cream or lidocaine injected into the skin. There is no specific risk to this procedure, but it can cause some bleeding and/or discomfort at the biopsy site and may leave a small scar.

What will happen with the samples stored for "biobanking"?

The samples stored in the EuroBioBank will be stored in a secure laboratory that is part of the EuroBioBank and belongs to the MRC Neuromuscular Centre BioBank in Newcastle. All the stored samples will be marked with a code and only selected staff will be able to de-code the samples to identify the name and date of birth of a sample’s donor. The only other patient information that will be attached to the samples will be the clinical and genetic diagnosis, and the age. This is all anonymous information, which will be entered in a sample “catalogue” that is publicly accessible from the EuroBioBank website, www.eurobiobank.org. This catalogue will allow researchers to view what samples are potentially available for their research. Researchers wishing to receive biological samples from the Newcastle part of EuroBioBank, must obtain approval from the MRC BioBank. The samples collected from this clinical outcome study will have a special code, which will indicate that they are linked to the International Dysferlinopathy Registry (see the question "What is the International Dysferlinopathy Registry?" below for more information), www.dysferlinregistry.org, through which additional valuable clinical information can be requested. Samples will be kept in the EuroBioBank for an indefinite period of time, unless the patient requests withdrawal of their samples.

When did the study start and how long will the study last?

The study began recruiting in the fall 2012 and recruitment continued until October 2014. It is anticipated that the last participant will have their final visit in Dec 2017.

How long is the study and how often will I have to go?

The study involves 6 visits over 3 years.  The visits are screening, baseline (approximately one month after the screening visit) and then 6 months, 12 months, 24 months, and 36 months post baseline.

What if I have started the study but then want to withdraw?

You have the right to withdraw from the study and to have your stored samples withdrawn from the EuroBioBank at any time without being asked to give a reason. This will not affect your care in any way. You can also take part in the clinical outcome study without donating samples to the EuroBioBank.

Who is running the study?

Oversight and funding for the clinical outcome study for dysferlinopathy (estimated at 2.5 million USD) is provided by the Jain Foundation, www.jain-foundation.org.  The study is led and coordinated across all sites by Prof. Kate Bushby and her study team at Newcastle University, with Newcastle upon Tyne Hospitals NHS Foundation Trust being the responsible hospital for the study.  Below is the contact information for the study leaders:

 

Jain Foundation Representative: 

Laura Rufibach, PhD 

Director of Research and Clinical Strategies

Jain Foundation

9725 Third Avenue NE

Suite 204

Seattle, Washington 98115

United States of America

Tel: +1-425-882-1492

Email:  Lrufibach@jain-foundation.org   

Overall Priniciple Investigator:

Prof. Kate Bushby, MD

Institute of Genetic Medicine

Newcastle University

International Centre for Life

Central Parkway

Newcastle upon Tyne

NE1 3BZ, United Kingdom

Tel: +44 (0)191 241 8737

Email: Kate.Bushby@newcastle.ac.uk

 

Study Project Manager:

Heather Hilsden

Institute of Genetic Medicine

Newcastle University

International Centre for Life

Central Parkway

Newcastle upon Tyne

NE1 3BZ, United Kingdom

Email:  Heather.Hilsden@newcastle.ac.uk

 

Who should I contact with questions?

If you have any questions about the clinical outcome study for dysferlinopathy, please contact us by emailing contact@dysferlinoutcomestudy.org or by contacting the your study site.

Why do I need to complete all 6 visits?

If you do not complete all 6 visits, your data will not be able to be used in the final analysis.