HIFU vs RAI in the Relapsed Graves' Disease

NCT03013257 | Completed DMC

• 1 other identifier: UW 16-565
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

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 treatment option for patients who are indicated for RAI but do not wish to have it because of one reason or another. HIFU appears to induce a faster disease remission and lessen the need of deferring pregnancy and radiation precautions because of the absence of radioactivity.

Conditions

Graves Disease

Keywords

Relapsed Graves' disease; High Intensity Focused Ultrasound; RAI

Outcome Measures

Primary Outcomes (1)

• Rate of remission

  Stating of biochemically euthyroid and hypothyroid without ATDs after 6 months of treatment

  6 months

Secondary Outcomes (9)

• Incidence of treatment-related morbidities from day-0 to post 2-week

  2 weeks

• Change in auto-antibodies

  6 months

• Change in total thyroid volume

  6 months

• Change in eye disease activity

  6 months

• Satisfaction score after treatment

  6 months

Study Arms (2)

High Intensity Focused Ultrasound

EXPERIMENTAL

Try to use the machine 'Echopulse' with High Intensity Focused Ultrasound to treat the relapsed Graves' disease

Device: Echopulse

Fixed-dose radioiodine-131

NO INTERVENTION

Using the traditional treatment, fixed-dose radioiodine-131, to treat the relapsed Graves' disease

Interventions

Echopulse DEVICE

Replacing HIFU for the Graves' disease patients who traditionally have RAI to remission

Also known as: High Intensity Focused Ultrasound (HIFU)

High Intensity Focused Ultrasound

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of GD based on standard clinical criteria (elevated thyroid hormone levels, suppressed TSH, positive TSHR auto-antibody, diffuse goiter ± high RAI uptake).
• Aged between 18 and 70 years old at the time of informed consent
• Have had at least one GD relapse. A relapse is defined as recurrent or persistent hyperthyroidism despite completing a continued course of ATDs for 18 months or more.
• Indicated for RAI treatment
• Valid consent is obtained

You may not qualify if:

• Prefer or have clear indications for surgery (such as those with large compressive goiter, suspected or documented thyroid malignancy, wishing to become pregnant within 6 months or with moderate to severe GO).
• Have pre-existing vocal cord palsy
• Are unable to move or extend their neck
• Have either right, left or central (isthmic) lobe measuring \>30ml in volume on pre-treatment USG volumetry (see later)
• Have concomitant thyroid nodules which are either indeterminate, suspicious of malignancy or proven malignant on fine needle aspiration cytology (FNAC).
• Have active or severe Graves ophthalmopathy (GO)
• Are pregnant, lactating or planning for pregnancy within 6 months
• Have any medical conditions that would make them too ill to undergo intravenous sedation or treatment
• Any condition that is unstable or can jeopardize the safety of the patients and their compliance to the study

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, 852, Hong Kong

Location

Related Publications (22)

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  PMID: 19652233 BACKGROUND

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  PMID: 26612446 BACKGROUND

• Palit TK, Miller CC 3rd, Miltenburg DM. The efficacy of thyroidectomy for Graves' disease: A meta-analysis. J Surg Res. 2000 May 15;90(2):161-5. doi: 10.1006/jsre.2000.5875.

  PMID: 10792958 BACKGROUND

• Von Hofe SE, Dorfman SG, Carretta RF, Young RL. The increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter. J Nucl Med. 1978 Feb;19(2):180-4.

  PMID: 627898 BACKGROUND

• Leslie WD, Ward L, Salamon EA, Ludwig S, Rowe RC, Cowden EA. A randomized comparison of radioiodine doses in Graves' hyperthyroidism. J Clin Endocrinol Metab. 2003 Mar;88(3):978-83. doi: 10.1210/jc.2002-020805.

  PMID: 12629071 BACKGROUND

• Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM; European Group on Graves' Orbitopathy (EUGOGO). Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol. 2008 Mar;158(3):273-85. doi: 10.1530/EJE-07-0666. No abstract available.

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  PMID: 22999130 BACKGROUND

Related Links

• Hong Kong Radiation Ordinance Chapter 303
• Revisions to List of charges: G.N. 1488 to Gazette No. 12/2013

MeSH Terms

Conditions

Graves Disease

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Study Officials

• Hung Hin, Brian Lang, MBBS(Hons)

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Associate Professor

Study Record Dates

• First Submitted: January 4, 2017
• First Posted: January 6, 2017
• Study Start: April 25, 2017
• Primary Completion: April 30, 2020
• Study Completion: June 30, 2020
• Last Updated: May 18, 2022

Record last verified: 2022-05

Locations

HK (1)