Frequently Asked Questions

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.

The outcome measures identified in this study are needed for the development and success of future clinical trials. In addition, the information collected in this study will provide a better understanding of dysferlinopathies, ensuring optimal care and treatment is being provided for people with these conditions, and will hopefully lead to new and better therapies.

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.

For the clinical outcome study, you will be assessed on 6 occasions over 3 years.  Each visit will likely last one entire day, possibly two.  The first visit will be a screening visit to assess eligibility.  Once you are determined to be eligible, the second visit (baseline) will likely occur a month or so after the screening visit.  After the baseline visit, you will be assessed again at 6 months, 12 months, 24 months and 36 months post baseline.  A variety of assessments will be performed at each visit according to your 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 will also collect blood samples and perform “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.

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.

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.

• All ambulant and non-ambulant patients age 10 and older.

• Patients with 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. If you do not have dysferlin mutations identified, the Jain Foundation sponsors the necessary tests. Please contact Esther Hwang, Director of Patient Relations and Diagnostics, by email at ehwang@jain-foundation.org or by phone at (425) 882-1440.

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 database that is linked to the International Dysferlinopathy Registry, www.dysferlinregistry.org. If you have specifically consented for it, then blood and skin samples will also be taken for storage in the MRC Neuromuscular Centre BioBank. See the questions "What is the International Dysferlinopathy Registry" and "What is 'biobanking'?" below for more information.

The information in the registry/database will be subject to the regulations on data protection (national laws related to EU directive 95/46) and will be confidential. Your data will not be made available to employers, governmental organizations, insurance companies or educational institutions, nor to your spouse, other family members or your doctor, unless you have given explicit consent to do so. The results of the clinical outcome study will be published, but you will not be able to be identified from the information published. Through a designated Registry Oversight Committee, academics, pharmaceutical companies and other third parties will be able to submit applications to access selected registry/database data that are anonymised and can comprise genetic and clinical data. Upon approval, these data will be provided to the requesting party in the form of a written data-analysis report, but no direct access to the registry/database will be given to them.

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.

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.

No, the study and all related assessments are free for all participants.  Funds are also available for the participant and a helper if necessary to travel to the nearest study center.

The study will begin recruiting patients in fall 2012.

You do not have to agree to take part in this study or to donate samples (blood and/or skin) for the EuroBioBank; your participation and donation are completely voluntary. If you do not wish to participate or donate, your care will not be affected in any way. You can also take part in the clinical outcome study without donating samples to the EuroBioBank.

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. If you choose to withdraw from the study, we will not use any data already collected about you. You can also request to have your study data be completely anonymised by having them disconnected from the International Dysferlinopathy Registry, www.dysferlinregistry.org.

All the collected data will be stored in a database that is linked to the International Dysferlinopathy Registry, www.dysferlinregistry.org. See the question "What is the International Dysferlinopathy Registry?" above for more information.

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: