A Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Relapsed Graves' Disease

Study Overview
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Brief Summary
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To evaluate the short-term efficiency and safety of HIFU treatment in the relapsed Graves' disease.

Detailed Description
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Grave's disease is the most common cause of hyperthyroidism and affects approximately 2% of women and 0.2% of men in the population. The use of antithyroid drugs (ATD) has been the first-line of treatment for Graves' disease in many centers for decades, and its use has been increasing worldwide. One reason for this is that it may induce remission, whereas radioiodine (RAI) and surgery often lead to hypothyroidism and other complications in addition to hospitalization and radiation exposure. However, ATD use is also associated with increasing risk of some adverse minor effects such as skin rash, gastric intolerance, and arthralgia in 5% of patients. Furthermore, major adverse events, such as agranulocytosis and hepatotoxicity may be life-threatening but are rare (<0.5% of cases). These usually occur during the first three to six months of treatment, and tend to be associated with high ATD doses. Therefore, the recommended duration of ATD treatment is generally not longer than 12-24 months. However, despite adequate medical treatment, up to 50-70% of patients with Graves' disease would relapse or recur and therefore, a more definitive approach using RAI treatment or thyroid surgery is eventually needed for the resolution of hyperthyroidism. Although RAI is considered safe and easy to manage, particularly in patients without Grave's ophthalmopathy (GO), subclinical and overt hypothyroidism may occur months or even years after the administration of RAI. Hence, long-term follow-up of thyroid function and GO as well as management of thyroxine replacement is necessary. Similarly, although surgery is the main therapeutic strategy, it carries a 2%-10% risk of complications such as hypocalcemia, transient or permanent recurrent laryngeal nerve palsy, bleeding, or postoperative infection. In view of these, various nonsurgical, minimally invasive treatment alternatives have been developed at specialized treatment centers. High-intensity focused ultrasound (HIFU) is a noninvasive procedure that involves application of a focused high-energy ultrasound beam for thermal tissue ablation inside the targeted zone, with minimal effect on the surrounding tissue. This method has been applied for treatment of a variety of medical conditions such as uterine fibroids and prostate, breast, pancreatic, and liver tumors. A favorable outcome also has been observed in patients with primary or secondary hyperparathyroidism. HIFU has also been proposed for thyroid nodule ablation . In a human feasibility study, 25 patients were treated 2 weeks before a scheduled thyroidectomy. Pathologic analysis demonstrated targeted tissue destruction of 2%-80% without any damage to neighboring structures. To the investigators knowledge, studies of follow-up after HIFU ablation of Graves' disease have not been published, except for one report where two patients received a combination of microwave ablation and RAI. Thus, the purpose of this prospective study is to assess the short-term efficacy and safety of US-guided HIFU ablation for the treatment of relapsed Graves' disease.

Official Title
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A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Relapsed Graves' Disease

Conditions
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Rrelapsed Graves' Disease

Intervention / Treatment
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* Device: HIFU Graves


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age older than 18 years; relapsed Graves' disease despite an adequate ATD treatment for 18 months or more; HIFU accessibility of the targeted area (distance between the skin and the anterior surface of the nodule less than 10 mm; with no interference of the collarbone with HIFU unit movements); normal thyrotropin concentration before procedure; on at least 2-week of β-blockade prior to HIFU; and absence of vocal cord immobility at laryngoscopy. Exclusion Criteria: patients who prefer or indicated for surgery; head and/or neck disease preventing hyperextension of the neck; history of thyroid cancer or other malignant tumors in the neck region; history of neck irradiation; severe Grave's ophthalmopathy (GO); large compressive goiter; pregnancy or lactation; and any contraindication related to intravenous moderate sedation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIFU Graves<br>Applying the High intensity Focused Ultrasound treatment to the relapsed Graves' disease Patients. | Device: HIFU Graves<br>* The HIFU treatment technique will be applied to the recruited participants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission rate of Graves' disease after one successful course of HIFU | To evaluate the remission rate of relapsed Graves' disease after 6 months of HIFU treatment | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The pain assessment (scoring 1-10) after treatment | Patient pain score immediately after HIFU treatment. | 6 months | 
| Incidence of local or general adverse events | The incidence rate of local or general adverse events after completion of HIFU treatment session. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIFU, Graves' disease, treatment