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

Rrelapsed Graves' Disease Clinical Trial

— HIFURGD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02685514
• Other study ID #: UW16-015
• Status: Completed
• Phase: N/A
• First received: February 14, 2016
• Last updated: November 9, 2016
• Start date: October 2015
• Est. completion date: April 2016

Study information

• Verified date: November 2016
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ß-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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graves Disease
• Rrelapsed Graves' Disease

Intervention

Device:
• HIFU Graves
The HIFU treatment technique will be applied to the recruited participants

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (13)

Cooper DS. Antithyroid drugs. N Engl J Med. 2005 Mar 3;352(9):905-17. Review. — View Citation

Esnault O, Franc B, Chapelon JY. Localized ablation of thyroid tissue by high-intensity focused ultrasound: improvement of noninvasive tissue necrosis methods. Thyroid. 2009 Oct;19(10):1085-91. doi: 10.1089/thy.2009.0121. — View Citation

Esnault O, Franc B, Ménégaux F, Rouxel A, De Kerviler E, Bourrier P, Lacoste F, Chapelon JY, Leenhardt L. High-intensity focused ultrasound ablation of thyroid nodules: first human feasibility study. Thyroid. 2011 Sep;21(9):965-73. doi: 10.1089/thy.2011.0141. — View Citation

Esnault O, Franc B, Monteil JP, Chapelon JY. High-intensity focused ultrasound for localized thyroid-tissue ablation: preliminary experimental animal study. Thyroid. 2004 Dec;14(12):1072-6. — View Citation

Esnault O, Rouxel A, Le Nestour E, Gheron G, Leenhardt L. Minimally invasive ablation of a toxic thyroid nodule by high-intensity focused ultrasound. AJNR Am J Neuroradiol. 2010 Nov;31(10):1967-8. doi: 10.3174/ajnr.A1979. — View Citation

Huh JY, Baek JH, Choi H, Kim JK, Lee JH. Symptomatic benign thyroid nodules: efficacy of additional radiofrequency ablation treatment session--prospective randomized study. Radiology. 2012 Jun;263(3):909-16. doi: 10.1148/radiol.12111300. — View Citation

Korkusuz H, Happel C, Koch DA, Gruenwald F. Combination of Ultrasound-Guided Percutaneous Microwave Ablation and Radioiodine Therapy in Benign Thyroid Disease: A 3-Month Follow-Up Study. Rofo. 2016 Jan;188(1):60-8. doi: 10.1055/s-0041-106538. — View Citation

Kovatcheva R, Vlahov J, Stoinov J, Lacoste F, Ortuno C, Zaletel K. US-guided high-intensity focused ultrasound as a promising non-invasive method for treatment of primary hyperparathyroidism. Eur Radiol. 2014 Sep;24(9):2052-8. doi: 10.1007/s00330-014-3252-4. — View Citation

Kovatcheva RD, Vlahov JD, Shinkov AD, Borissova AM, Hwang JH, Arnaud F, Hegedüs L. High-intensity focused ultrasound to treat primary hyperparathyroidism: a feasibility study in four patients. AJR Am J Roentgenol. 2010 Oct;195(4):830-5. doi: 10.2214/AJR.09.3932. — View Citation

Kovatcheva RD, Vlahov JD, Stoinov JI, Kirilov GG, Krivoshiev SG, Arnaud F, Ortuno C, Drüeke TB. High-intensity focussed ultrasound (HIFU) treatment in uraemic secondary hyperparathyroidism. Nephrol Dial Transplant. 2012 Jan;27(1):76-80. doi: 10.1093/ndt/gfr590. — View Citation

Watanabe N, Narimatsu H, Noh JY, Yamaguchi T, Kobayashi K, Kami M, Kunii Y, Mukasa K, Ito K, Ito K. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease. J Clin Endocrinol Metab. 2012 Jan;97(1):E49-53. doi: 10.1210/jc.2011-2221. — View Citation

Yip J, Lang BH, Lo CY. Changing trend in surgical indication and management for Graves' disease. Am J Surg. 2012 Feb;203(2):162-7. doi: 10.1016/j.amjsurg.2011.01.029. — View Citation

Zhou YF. High intensity focused ultrasound in clinical tumor ablation. World J Clin Oncol. 2011 Jan 10;2(1):8-27. doi: 10.5306/wjco.v2.i1.8. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	The pain assessment (scoring 1-10) after treatment	Patient pain score immediately after HIFU treatment.	6 months	Yes
Secondary	Incidence of local or general adverse events	The incidence rate of local or general adverse events after completion of HIFU treatment session.	6 months	Yes