HIFU Ablation vs Fixed-dose RAI-131 Therapy in Moderate-sized Non-toxic MNG
Condition: Non Toxic Multinodular Goiter; High Intensity Focused Ultrasound; RAI
MeSH terms: Goiter
Study type: Interventional

Summary: 
      After obtaining informed consent, eligible subjects will be assigned randomly into either
      High intensity focused ultrasound group (HIFU) or Radioactive iodine (131I) therapy group
      (RAIT). After treatment, they will be followed up for 4 visits (1-month, 3-month, 6- month,
      12-month of post treatment). At each visit, they will have physical examination, regular
      blood test and questionnaire to evaluate their quality of life. The collected data will be
      used to compare the effectiveness between HIFU and RAIT for non-toxic multi-nodular goiter
      (NMNG). The primary purepose is to find out the best non-invasive way in treating NMNG.

      For HIFU, you may experience:

        1. Mild bruising and redness at the site of treatment

        2. Edema of the skin tissue

        3. Pain/discomfort during the procedure

        4. Skin burns but rare (<1%)

        5. Vocal cord paresis on the side of the treated lobe but rare (<1%)

        6. Unintentional damage to the surrounding tissue (outside the planned treatment area).

      For RAIT, you may experience neck tenderness or sore throat in the following few days as
      developing moderate inflammation in the thyroid and producing discomfort in the neck or
      throat area. Your symptoms may turn worse for first few week, but will improve over weeks.
    

Detailed description: 
      Non-toxic multinodular goiter (NMNG) is a condition referred to as a nodular enlargement of
      the thyroid gland due to the presence of two or more nodules without clinical hyper- or
      hypothyroidism. It is undoubtedly one of the most common thyroid disorders worldwide and it
      is estimated that more than 5% of the female population have a clinically-palpable NMNG
      (1,2).

      Although the majority of NMNGs do not cause symptoms and therefore, do not require any
      intervention other than simple surveillance, some can cause local pressure symptoms and
      cosmetic concerns over time (1-3).

      For NMNGs that cause symptoms, the most widely-accepted treatment has been surgical resection
      either in the form of a hemithyroidectomy or total thyroidectomy. Despite being safe when
      done in experienced hands, surgery is associated with complications such as recurrent
      laryngeal nerve injury and hypoparathyroidism, both of which can be permanent. In addition, a
      general anesthesia is almost inevitably required when surgery is performed. As a result,
      non-surgical thermal ablation techniques have been increasingly recognized as an alternative
      treatment in symptomatic NMNG (4). These ablation techniques utilize thermal energy to cause
      shrinkage of adenomatous nodules and thereby, relieve symptoms. Types of ablation include
      radiofrequency, laser and microwave ablations and more recently, high intensity focused
      ultrasound (HIFU). Regardless of which ablation technique, they have all been shown to not
      only induce significant nodule shrinkage but also alleviate symptoms (4-6). Radioactive
      iodine (131I) therapy (RAIT) is another promising non-surgical alterative which is
      recommended in patients who refuse or have contraindications for surgery. Despite being a
      less recognized treatment in both Asia and North America, this treatment has increasingly
      been adopted. In some European countries such as Denmark and Netherlands, it has replaced
      surgery as the treatment of choice in moderately-sized NMNG as recommended in
      recently-published clinical practice guidelines (1,7,8). However, RAIT has limitations. For
      example, it is less applicable in very large-sized NMNG (>100 mL) because large goiters tend
      to have a lower radioiodine uptake leading to suboptimal shrinkage. Also considerable
      inconsistency in goiter shrinkage has been reported (7). With our population getting older
      and the general public placing a greater emphasis on preserving organ function and
      lessinvasive treatments, non-surgical treatment alternatives will have an increasing role in
      the future treatment of NMNG. To our knowledge, it remains unknown whether one particular
      treatment modality is superior over the other modality because there has not been any direct
      comparison between the two modalities. Only one previous study compared treatment efficacy
      between laser ablation and RAIT. However, it mainly focused on the treatment of toxic thyroid
      nodules (9). To enhance treatment efficacy, a recent study reported promising results of
      combining the effect of thermal ablation and RAIT (10).
    

Intervention name(s): Echopulse; Radioactive iodine (Radioidine i131)
Intervention type(s): Device; Radiation
Intervention description(s): Echopulse is a real-time US-guided High-intensity focused ultrasound (HIFU) system, the HIFU session 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; Radioactive iodine (RAI) is a radioactive form of iodine that for ablation in thyroid disease (i.e. Graves' disease or few thyroid cancer)
Other intervention name(s): High Intensity Focused Ultrasound (HIFU)
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: group 1 is for HIFU treatment, group 2 is for RAI treatment
Masking: None (Open Label)
Primary purpose: Health Services Research