HIFU Ablation vs Fixed-dose RAI-131 Therapy in Moderate-sized Non-toxic MNG

May 19, 2022 updated by: Dr. Lang Hung Hin, Brian, The University of Hong Kong

A Randomized, Open-label, Parallel-group Study to Determine the Efficacy of Sequential High-intensity Focused Ultrasound (HIFU) Ablation Versus Fixed-dose Radioiodine-131 Therapy in Moderate-sized Non-toxic Multinodular Goiter

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

156

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have a moderate-sized NMNG. The dimension of the largest nodule cannot exceed 50mm in diameter. Also on USG volumetry, the total combined volume of the three largest nodules (i.e. the largest nodule volume + second largest nodule volume + third largest nodule volume) or in short, TNV cannot exceed 80 mL or cm^3.
  • The NMNG has to benign. Each nodule within the goiter will be carefully evaluated on USG by an experienced clinician to look for suspicious features for malignancy. Suspicious-looking nodules will be biopsied by USG-guided FNAC. Only nodules with Bethesda II on FNAC will be considered benign.
  • Aged between 18 and 70 years old at the time of informed consent.
  • Have genuine cosmetic and/or pressure symptoms.
  • Have to have normal serum free T4 (FT4) and thyroid-stimulating hormone (TSH) levels.

Exclusion Criteria:

  • Have a non-toxic diffuse goiter or a NMNG with the largest nodule < 20mm in diameter.
  • Prefer or have a clear indication for thyroidectomy (such as rapidly growing, compressive goiter or suspected or documented thyroid malignancy).
  • Have a pre-existing vocal cord palsy.
  • Unable to tolerate even slight neck extension during HIFU ablation.
  • Pregnant, lactating women or women wishing to become pregnant within 6 months.
  • Previous thyroid surgery or neck irradiation.
  • Family history of non-medullary thyroid carcinoma.
  • Have any medical conditions that would make them too ill to undergo treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: HIFU on NMNG
The patients with non-toxic multinodular goiter are assigned to have high intensity focused ultrasound treatment.
Device: Echopulse
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
Other Names:
  • High Intensity Focused Ultrasound (HIFU)
Active Comparator: RAI on NMNG
The patients with non-toxic multinodular goiter are assigned to have radioactive iodine (i131) treatment.
Radiation: Radioactive iodine (Radioidine i131)
Radioactive iodine (RAI) is a radioactive form of iodine that for ablation in thyroid disease (i.e. Graves' disease or few thyroid cancer)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The absolute change in Thyroid nodule volume (TNV) after sequential HIFU treatment and a fixed-dose (370MBq) RAIT after 12 months.
Time Frame: 12 months
To compare the absolute change in Thyroid nodule volume (in cm^3) after sequential HIFU treatment and a fixed-dose (370MBq) RAIT after 12 months.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in total thyroid volume (TTV) (in cm^3)
Time Frame: 12 months
To compare the absolute change in TTV between HIFU and RAIT groups
12 months
Change in the largest/dominant nodule dimensions
Time Frame: 12 months
To compare the change in the largest/dominant nodule dimensions (in cm) between HIFU and RAIT groups
12 months
Incidence of treatment-related morbidities after HIFU/RAIT
Time Frame: 12 months
To compare incidence of treatment-related morbidities and hypothyroidism between HIFU and RAIT groups
12 months
Change in World Health Organization goiter grade
Time Frame: 12 months
To compare WHO goiter grade over time between HIFU and RAIT groups
12 months
Change in symptom improvement score
Time Frame: 12 months
To compare symptom improvement score (0-10) over time between HIFU and RAIT groups
12 months
Change in pressure symptom score
Time Frame: 12 months
To assess the changes in pressure symptom score (by Visual Analogue Scale, VAS, scoring from 0-10, 0 is for no pressure and 10 is for the maximum pressure feeling as subjects' view) over time between the HIFU and RAIT groups.
12 months
Change in quality of life
Time Frame: 12 months
To assess the changes in quality of life (QOL) using by "12-Item Short Form Survey (SF-12) (VERSION 2.0)" between the two treatment groups. SF-12 is scoring 70 in total, the higher score represent higher quality of life.
12 months
Change in patient satisfaction
Time Frame: 12 months
To assess the changes in patient satisfaction (by Visual Analogue Scale, VAS, scoring from 0-10, 10 is for the maximum score representing well satisfaction) between the two treatment groups
12 months
Compare the costs (in dollars)
Time Frame: 12 months
To compare the direct and indirect costs between HIFU and RAIT (in dollars)
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Investigators

  • Principal Investigator: Hung Hin Brian Lang, MBBS(Hons), The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2020

Primary Completion (Actual)

February 20, 2022

Study Completion (Actual)

April 30, 2022

Study Registration Dates

First Submitted

June 26, 2019

First Submitted That Met QC Criteria

July 3, 2019

First Posted (Actual)

July 5, 2019

Study Record Updates

Last Update Posted (Actual)

May 20, 2022

Last Update Submitted That Met QC Criteria

May 19, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 19-016

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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