People will have checks to make sure they have both diabetes mellitus and optic atrophy; a genetic test result; enough vision at the start of the study to be able to assess the effects of treatment; and safety checks.
Possible benefits of taking part
Taking part in a clinical trial can be helpful if the trial medicine works to slow down the progress of the disease. However there is no guarantee that this will happen. There may be benefits in being seen by the study team regularly, as they will monitor the Wolfram disease carefully and treat any complications if they happen.
Possible risks of taking part
Any medicine in a clinical trial may not work, and not slow down the disease; and every medicine has side effects. Sometimes these side effects may be serious or life threatening. Before deciding whether or not to take part, always read the participant information sheets carefully, and ask about possible side effects.
How will we know if a medicine works in Wolfram?
We asked patient support groups in the UK, USA, Spain, and France, to advise us what are the most important outcome measures for trials of new treatments. Each group ranked vision as the most important. This means that any treatment must slow down or stop the worsening of vision.
Prof Tamara Hershey has shown that in people with Wolfram, parts of the brain slowly get smaller with age. This is related to problems with balance. With her kind help, we are using brain scans, to check that any treatment can slow down or stop parts of the brain getting smaller.
In Wolfram, vision gets worse, and parts of the brain get smaller, over years rather than months. In order to show that a treatment works, we need to give the treatment for several years. This is why the Phase II trial of sodium valproate involves giving people the medicine for 3 years.
If it is clear that a medicine in a clinical trial is working, it is possible to stop the trial early and give everyone the medicine.
Can I take these medicines without taking part in a trial?
The medicines being used in the clinical trials are not licensed for use in Wolfram. This means that doctors are not allowed to prescribe them to treat Wolfram syndrome. The reason is that no-one has done studies to show they are safe and to show they work in Wolfram. If a person with Wolfram took one of these medicines outside a trial, and had a serious side effect, the clinical trial would automatically be stopped. If this were to happen, we would never know if these medicines may work in Wolfram.
Future plans for studies
If Dr Urano’s safety study of Dantrolene shows that it is safe, he will then apply for a Phase II study to see if it works in Wolfram. The design of this study will be similar to the Sodium Valproate study above.
We are also seeking European Medicines Agency advice about the design of a Phase III clinical trial comparing Dantrolene Sodium to Valproate and in combination in Wolfram. If this is funded, it will start after the current studies have finished. It will recruit up to 140 people with Wolfram worldwide.
We are very grateful to the following people who gave us their time and helped with this research update letter:
A. Profs Hershey, Marshall, Hamel, Mlynarski, Esteban, OrCAD, Dias, Wright.
B. Wolfram Study Groups in Washington and Birmingham Universities, Boyd Consultants.
C. St. Louis Children’s, Barnes Jewish, Birmingham Children’s, and University Hospital Birmingham
D. Our fantastic family support groups Snow and Ellie White Foundations, Wolfram syndrome UK, Spanish and French associations, Wellchild.