RecruitingPhase IIIInterventional

Rituximab in Graves’ disease 2

Graves’ disease (GD) is one of the more common disorders of the thyroid gland, affecting 700 young people in the UK each year. In GD, the immune system mistakenly makes antibodies that stimulate the thyroid, causing it to produce too much thyroid hormone. This can have a profound impact on physical health, quality of life, attention span and education or work performance. Treating GD is more difficult in the young because standard antithyroid drug therapy (ATD), typically using carbimazole (CBZ), is more likely to result in side-effects and less likely to result in cure when treatment is stopped. Only 1 in 4 patients will require no further treatment after 2 years of CBZ. Other treatment options if the GD recurs are surgery (total thyroidectomy) or radioactive iodine. These are associated with additional risks and greater costs in the young, necessitate life-long thyroid hormone replacement and reduced quality of life. Rituximab (RTX) medication is used to treat many immune disorders. It works by targeting blood cells that make antibodies responsible for attacking body tissues including the thyroid. A recent exploratory study in young patients with GD suggested that giving one dose of RTX in addition to standard ATD is well tolerated and may increase the likelihood of remission. We are carrying out a clinical trial throughout the UK, where 124 young people with GD, aged between 12-24 years, will be randomly allocated to one of two different groups: 1) A 2-year course of ATD 2) 1 dose of RTX as well as 2 years of ATD. Participants will not know which group they are in. They will have bloods taken to check thyroid function at 4 weeks and then every 8 weeks in the first year and 3- monthly thereafter. The visit frequency is similar to standard care. The primary outcome will be a comparison of young people in each group with normal thyroid function and who have had no further treatment 12 months after stopping ATD.

At a glance

Status

Recruiting

Phase

Phase III

Sponsor

Newcastle upon Tyne Hospitals NHS Foundation Trust

Enrolment target

124

Start

31 Jul 2025

Estimated completion

31 Oct 2026

Medical condition: Graves disease Medical condition in lay language: Graves Disease (autoimmune hyperthyroidism). Therapeutic areas: Diseases [C] - Immune System Diseases [C20]

What is this study about?

Graves' disease is a condition where your immune system mistakenly tells your thyroid gland to produce too much hormone. This can cause a range of symptoms like losing weight, feeling shaky, having a fast heart rate, and feeling hot or sweaty. It can really affect how you feel, your energy levels, and even your school or work.

Treating Graves' disease in young people can be tricky. Standard tablet medication often has side effects, and it doesn't cure everyone – only about 1 in 4 young people are cured after two years. If it comes back, options like surgery or radioactive iodine are available, but these have their own risks and mean you'd need hormone medication for life. This study is testing a different approach using a drug called rituximab.

Rituximab is already used for other immune conditions. It works by targeting specific cells in your blood that are responsible for attacking your thyroid in Graves' disease. A small study has hinted that giving just one dose of rituximab alongside the usual tablets might help more young people achieve a long-lasting normal thyroid function. This larger study aims to properly test if this is true and if it could become a new part of standard treatment.

Key takeaways

Tests if a single rituximab dose improves Graves' treatment for young people.
Compares rituximab plus tablets to tablets alone.
Aims to increase chances of normal thyroid function long-term.
Open to 12-24 year olds newly diagnosed with Graves' disease.
Involves extra hospital visits and a three-hour drip for one group.
Could lead to better standard treatments for the future.

Who may be eligible?

This study is looking for young people aged between 12 and 24 years old who have been diagnosed with Graves' disease. You would need to be starting treatment with new anti-thyroid tablets (like carbimazole or propylthiouracil) for the first time, within the last 12 weeks. Your blood tests must show that your thyroid hormones are high and that your immune system is causing the problem.

There are also some reasons why you wouldn't be able to join. For example, if you've had Graves' disease before, have a serious ongoing infection, or if your immune system is already very weak. You also can't take part if you're pregnant, planning to become pregnant during the study, or if you're breastfeeding. If you've previously taken certain strong immune-suppressing drugs, you wouldn't be suitable either.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you between 12 and 24 years old?
Have you recently been diagnosed with Graves' disease?
Are you starting anti-thyroid tablets for the first time (within the last 12 weeks)?
Are you not pregnant, breastfeeding, or planning a pregnancy during the study?
Do you not have any other severe or long-term health conditions?
Are you willing to commit to a 3-year study period?

Answer every question to see your result.

What does participation involve?

If you join this study, you'll be randomly put into one of two groups, like flipping a coin. You'll either receive the usual two-year course of anti-thyroid tablets, or you'll get the tablets plus a single treatment of rituximab.

The rituximab is given through a drip (like an IV bag) that takes about three hours. You won't know if you're getting rituximab or a salt water drip (a 'placebo') – this is so we can fairly see the drug's true effect. You'll have extra visits to the hospital compared to regular care, but we'll cover travel costs. We'll keep a close eye on your health and thyroid function throughout the study. The total study period is expected to last for three years.

Potential risks and benefits

It's important to know that we can't guarantee you'll directly benefit from taking part in this study. You might get the rituximab, or you might get the placebo, and it's possible rituximab won't be more effective than standard treatment. However, your involvement will provide vital information that could help improve future treatments for young people with Graves' disease. You'll also have closer contact with the research team, which some patients find reassuring. Potential risks include needing a cannula (a small tube in your vein) for the drip, which can be a bit painful though numbing cream will be offered. There's a very small, temporary risk of a weakened immune system from rituximab, and a very rare risk of a reaction during the drip, or a serious brain condition called PML. We will monitor you closely for all these things. If you are female, you must not become pregnant during the trial, and if you are male, your partner must not become pregnant. You can withdraw from the study at any time.

Locations (1)

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Approximate
-, England

Common questions

What is Graves' disease?

It's an autoimmune condition where your body's immune system attacks your thyroid gland, making it produce too much hormone.

What is rituximab?

It's a medication that targets specific immune cells that are involved in causing Graves' disease.

Will I definitely get rituximab?

No, you'll be randomly assigned to either receive rituximab plus standard treatment, or just standard treatment plus a salt water drip.

How long does the study last?

The study will last for three years in total, including your treatment and follow-up.

Can I stop participating if I change my mind?

Yes, you are free to withdraw from the study at any time without giving a reason.

How to find out more

Claire Wood

rigd2@newcastle.ac.uk - Official trial record

Always speak to your GP or specialist before deciding to take part in a study.