Clinical Trial: HIFU vs RAI in the Relapsed Graves' Disease

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomized, Open-label, Parallel-group Study to Explore the Efficacy of High-intensity Focused Ultrasound (HIFU) Versus Fixed-dose Radioiodine-131 in the Treatment of Relapsed Graves' Disease

Brief Summary:

Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies to the thyrotrophin (TSH) receptor on thyroid follicular cells. It is the most common cause of hyperthyroidism and approximately 3% of women and 0.5% of men develop GD in their lifetime.

RAI has been shown to be a cost-effective and safe therapy in patients with GD but with some disadvantages. In addition, despite its proven efficacy and safety, many patients do not wish to undergo RAI because of radiation fear and prefer to either continue ATDs or have surgery.

High-intensity focused ultrasound (HIFU) is a non-invasive procedure that involves the application of a high-energy focused beam for thermal tissue ablation within a targeted zone. Similar to the principle of RAI (i.e. using ionizing radiation to ablate thyroid parenchyma and cause GD remission), we postulated that the heat energy generated from HIFU could also be used to ablate the thyroid parenchyma and cause GD remission. The idea of using heat energy to ablate thyroid parenchyma minimally invasively was recently reported using radiofrequency ablation but to our knowledge, we are one of the first (if not the first) group to propose using HIFU energy to ablate thyroid parenchyma as a definitive treatment for relapsed GD.

Having obtained ethical approval, a pilot study was conducted to examine the efficacy and safety of HIFU as a treatment for relapsed GD. In the pilot study, all patients underwent a safe and successful HIFU ablation for relapsed GD. Based on the results of the pilot study, we hypothesize that a single HIFU treatment to the thyroid gland may be as effective as our standard outpatient fixed-dose of RAI (370MBq) in causing remission of GD at 6-month. If our hypothesis turns out to be true, HIFU could become a

Detailed Summary:

Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies to the thyrotrophin (thyroid stimulating hormone [TSH]) receptor on thyroid follicular cells. It is the most common cause of hyperthyroidism and approximately 3% of women and 0.5% of men develop GD in their lifetime1. In our locality, like Europe and Japan, antithyroid drugs (ATDs) such as carbimazole or propylthiouracil have been preferred over radioactive iodine (RAI) and surgery as the initial treatment of GD2-4. This is because ATDs are relatively easy to administer, could induce disease remission (30-70%) and avoid life-long thyroid hormone replacement, operative risks and radioactivity2-4. However, because of possible side-effects, they are only recommended for a period of 12 to 18 months. Taking ATDs for a longer period does not seem to increase the chance of remission5. Therefore, currently, once the disease has relapsed after a 18-month of ATD treatment, more definitive treatment modalities like RAI or surgery are indicated. Regarding to which is more preferable, surgery is usually advised in patients with large compressive goiter (>80g), suspected or documented thyroid malignancy, planning to become pregnant within 6 months and moderate to severe Graves' ophthalmopathy (GO)2-4. As a result, most patients without these conditions are considered for RAI2-4.

RAI has been shown to be a cost-effective and safe therapy in patients with GD4,6,7. In North America, clinical endocrinologists favor RAI as the initial treatment for GD2-4. However, since RAI is usually prescribed on an outpatient basis, it is necessary to consider nearby individuals' exposure doses and formulate radiation precautions carefully8. Other disadvantages include its slow induction of euthyroidism, potential worsening of GO and deferral of pregnancy2-4. Although various dosing techniques have been descri
Sponsor: The University of Hong Kong

Current Primary Outcome: Rate of remission [ Time Frame: 6 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Incidence of treatment-related morbidities from day-0 to post 2-week [ Time Frame: 2 weeks ]
  To examine any treatment-related morbidities after the treatment within 2 weeks.
• Change in auto-antibodies [ Time Frame: 6 months ]
  To examine the changes of anti-thyroid and TSHR after 6 months of treatment
• Change in total thyroid volume [ Time Frame: 6 months ]
  To measure the change in size of total thyroid volume after 6 months of treatment
• Change in eye disease activity [ Time Frame: 6 months ]
  To examine the change in eye disease activity (CAS) with 6 months.
• Satisfaction score after treatment [ Time Frame: 6 months ]
  To measure the satisfaction score (1-10) after treatment
• The pain assessment after treatment [ Time Frame: 6 months ]
  The pain assessment (scoring 1-10) after treatment
• Change in Quality of life [ Time Frame: 6 months ]
  To examine the change in qualitfy of life with SF-12 scores from baseline to 2-month and 6-month
• The medical costs [ Time Frame: 6 months ]
  To evaluate the cost of different treatments including direct medical costs (including treatment, investigations, unplanned readmission and visits) and indirect costs (such as number of days before returning to normal activities and work). Medical costs will be based on the latest Government Gazette.
• The effectiveness of HIFU treatment [ Time Frame: 6 months ]
  The effectiveness of HIFU will be quantified by quality-adjusted left years (QALYs), which will be calculated as the product of the average duration of that stage and SF-6D preference value (i.e. from SF-12) for the particular health state.

Original Secondary Outcome: Same as current

Information By: The University of Hong Kong

Dates:
Date Received: January 4, 2017
Date Started: May 2017
Date Completion: June 2019
Last Updated: April 28, 2017
Last Verified: April 2017