Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04009863
Recruitment Status : Not yet recruiting
First Posted : July 4, 2019
Last Update Posted : July 8, 2019
Sponsor:
Information provided by (Responsible Party):
Dr. Lang Hung Hin, Brian, The University of Hong Kong

Brief 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.


Condition or disease Intervention/treatment Phase
Non Toxic Multinodular Goiter High Intensity Focused Ultrasound RAI Device: Echopulse Radiation: Radioactive iodine (Radioidine i131) Not Applicable

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).


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
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
Official Title: 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
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Iodine

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 Name: 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)




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. Change in World Health Organization goiter grade [ Time Frame: 12 months ]
    To compare WHO goiter grade over time between HIFU and RAIT groups

  5. Change in symptom improvement score [ Time Frame: 12 months ]
    To compare symptom improvement score (0-10) over time between HIFU and RAIT groups

  6. 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.

  7. 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.

  8. 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

  9. Compare the costs (in dollars) [ Time Frame: 12 months ]
    To compare the direct and indirect costs between HIFU and RAIT (in dollars)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04009863


Contacts
Layout table for location contacts
Contact: Hung Hin Brian Lang, MBBS(Hons) +852-22554232 blang@hku.hk

Locations
Layout table for location information
Hong Kong
Queen Mary Hospital
Hong Kong, Hong Kong
Sponsors and Collaborators
The University of Hong Kong
Investigators
Layout table for investigator information
Principal Investigator: Hung Hin Brian Lang, MBBS(Hons) The University of Hong Kong

Publications:
Royal College of Physicians. Radioiodine in the management of benign thyroid disease: clinical guidelines. Report of a Working Party. London: RCP, 2007. Available from: http://www.thyroiduk.org.uk/tuk/guidelines/Radioiodine%20guidelines%202007.pdf
Hospital Authority. 2013. Revisions to List of charges: G.N. 1488 to Gazette No. 12/2013. In Hong Kong Government Printers. Available: http://www.gld.gov.hk/egazette/english/gazette/toc.php [Accessed at 1st February 2018]

Layout table for additonal information
Responsible Party: Dr. Lang Hung Hin, Brian, Clinical Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04009863     History of Changes
Other Study ID Numbers: UW 19-016
First Posted: July 4, 2019    Key Record Dates
Last Update Posted: July 8, 2019
Last Verified: July 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Thyroid Diseases
Endocrine System Diseases
Goiter
Iodine
Anti-Infective Agents, Local
Anti-Infective Agents
Trace Elements
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs