Clinical trial NCT02685514: A Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Relapsed Graves' Disease
Official title: A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Relapsed Graves' Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rrelapsed Graves' Disease
Keywords: HIFU
Graves' disease
treatment
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2016-02-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the short-term efficiency and safety of HIFU treatment in the relapsed Graves' disease.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Remission rate of Graves' disease after one successful course of HIFU
timeFrame: 6 months
Secondary outcomes:
measure: The pain assessment (scoring 1-10) after treatment
timeFrame: 6 months
measure: Incidence of local or general adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: The University of Hong Kong
name: Hung Hin, Brian Lang, MBBS(Hons)
role: PRINCIPAL_INVESTIGATOR
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