Background

Graves’ disease (GD), is the name for the condition in which your immune system attacks your thyroid gland and this causes overactivity. In its mild form, GD is conventionally treated with antithyroid tablets or radioactive iodine therapy, with satisfactory patient outcomes. However, around 25% of  individuals with GD have severe Graves’ disease, characterised by either rampant thyroid overactivity and debilitating symptoms which are resistant to conventional antithyroid tablets, significant thyroid enlargement (goitre), or involvement of the eyes (known as  thyroid eye disease or Graves’ orbitopathy) or the skin of the legs/feet (known as  thyroid dermopathy).  These symptoms may occur simultaneously in the same individual and usually predict that conventional treatment will not be successful and that there will be unsatisfactory treatment outcomes.

 

Individuals with severe GD typically undergo surgery both on their thyroid and more than once for correction of thyroid eye disease. Despite the best current treatments that doctors have to offer, residual facial disfigurement following Graves’ orbitopathy is common, and this has a huge social and societal impact. A less invasive treatment with better outcomes for such individuals is desperately needed.

 

Graves’ disease is directly caused by circulating auto-antibodies (known as TRAbs) that stimulate the thyroid to become overactive but also directly influence development of Graves’ orbitopathy. TRAbs are produced by plasma cells in the body and levels are markedly elevated in severe GD.  A better understanding of these TRAb-producing plasma cells in individuals with GD is essential, especially as we now have a drug (Daratumumab) which can potentially control these plasma cells. Daratumumab, at high doses, has been shown to be safe and successful at treating myeloma (a form of plasma cell cancer). We also need to determine whether Daratumumab, at much  lower doses, can reduce TRAb levels and impact on the severity and/or progression of Graves’ disease.

 

We would like your views about a research study that we are planning in the future. We need to know what you think now so we can make the study better for the participants and to get information from it that matters most for patients.

 

For the first part of this study we will obtain samples (blood, thyroid gland, bone marrow and neck lymph glands) from patients with varying severity of GD to have a better understanding of these TRAb-producing plasma cells before, during and after conventional GD treatment.

 

The second part of the study will involve 2 groups of patients with severe GD allocated to either receiving 2 infusions of low dose Daratumumab or placebo (saline) 2 weeks apart. Conventional treatment with antithyroid tablets and eye treatment will continue in both groups.  The main aim of this study is to determine how effectively Daratumumab can reduce TRAb levels.

Questions:      Please state your views about these statements: consider how you would feel if this study was being offered to you today. 

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* 1. I think the current treatment options for my Graves’ disease are:

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* 2. For the first part of the study: a fine needle sample from the thyroid gland and neck nodes can be obtained under ultrasound guidance and this can occasionally be uncomfortable but generally well tolerated.  A bone marrow sample is obtained with a needle from the pelvic bone at the base of the spine. The bone is numbed with local anaesthetic but pain can be felt for only a few seconds when taking the sample with the needle.
I would be happy to provide a blood sample:

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* 3. I would be happy to provide a thyroid/neck node sample

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* 4. I would be happy to provide a bone marrow sample

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* 5. I would be happy to provide a bone marrow sample during a general anaesthesia if I was being put to sleep for surgery on my thyroid or my eyes anyway.

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* 6. For the second part of the study: participants will be asked to attend the trials unit at RVI for 5 study visits over a period of 3 months. The infusions will last for 3 hours during 2 of the visits. The other visits will last 30 to 40 minutes.

I would be happy to attend for the duration of the study.

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* 7. I would volunteer for the study if I read about it in the local newspaper

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* 8. I would volunteer for the study if I read about it online through a patient forum or the British Thyroid Foundation.

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* 9. I would volunteer for the study if I heard about it through broadcast media (radio/TV)

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* 10. I would volunteer for the study only if my own doctor (GP) suggested it.

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