Clinical trial NCT03331172: HIFU Reapplication in Benign Nodules
Official title: Efficacy and Safety of High Intensity Focused Ultrasound (HIFU) Reapplication in Benign Thyroid Nodules That Had Less-than Adequate Shrinkage Following Single-session HIFU Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Thyroid Nodule
Keywords: HIFU
thyroid nodule
Benign
Reapplication
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2017-11-06
Enrollment: 28
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: High Intensity Focused Ultrasound (HIFU) is a new approach in treating benign thyroid nodule without surgery. It is proven effective and safe relative to traditional surgery. From previous HIFU studies, it caused shrinkage of thyroid nodule up to 70% from original size. Unfortunately, 5-10% of nodule do not shrink. Those which do not shrink are usually large in size and therefore a second HIFU treatment may help. This study is going to evaluate the efficacy and safety of reapplication HIFU after the first single HIFU session in 6 months.

The study will be carried out in the following steps:

1. Recruit subject from the clinic according to the study criteria.
2. Arrange the reapplication HIFU treatment within 3 months.
3. Arrange 4 visits after the HIFU treatment in Post 7 days, Post 1 month, Post 3 months, and Post 6 months; Data collection will be in these 4 visits through the questionnaire or interview by research assistant
4. The subjects will have further health management with the same team after the study.

Detailed description: Thyroid nodules are common and although most are benign and remain relatively static in size, some can grow and become large and cause local symptoms over time. In such scenario, thyroidectomy is usually indicated. However, surgery is not only associated with complications but also with high cost and general anesthesia. As a result, there has been a growing interest in exploring less invasive, non-surgical technique for benign thyroid nodules. For solid or predominantly-solid (\<30% cystic areas) thyroid nodules, thermal ablation techniques have been shown to be highly effective in causing nodule shrinkage and alleviating symptoms in the long-term. To date, numerous thermal ablation techniques have been described and they include radiofrequency ablation (RFA), percutaneous laser ablation (PLA), microwave ablation and more recently, high intensity focused ultrasound (HIFU). HIFU is now considered the least invasive technique as there is no need for needle insertion into the target lesion during treatment. It works by utilizing focused ultrasound energy to generate heat and induce thermal ablation beneath the skin and other tissue layers. Recent studies (including several from our group) have shown that it is effective in not only inducing significant nodule shrinkage but also in alleviating nodule-related symptoms.

However, despite its overall success, approximately 10 - 15% of solid or predominantly solid nodules do not shrink adequately (i.e. \<50% shrinkage from baseline in the first 6-12 months). Although the exact reason why some nodules do not respond remains unclear, it is noted that the majority of these less responsive nodules are larger in size / volume and so, a second or reapplication of ablation might be required to cause further shrinkage and improvement in symptoms \[11\]. However, the role of HIFU reapplication in nodules with less-than-adequate response (\<50% at 6 months) remains undefined. As a result, the present study is aimed to the feasibility and safety of HIFU reapplication in nodules with shrinkage \<50% of baseline volume 6 months after single-session HIFU treatment.

Eligibility criteria: Inclusion Criteria:

* patients age older than 18 years,
* a nodule that has previously been completely treated by single-session HIFU ablation but has not responded adequately (i.e. \<50% volume reduction from baseline after 6 months),
* a benign nodule without signs of malignancy (e.g, nonsuspicious clinical and US appearance, benign results at cytologic examination performed in the last 6 months, normal serum calcitonin level),
* a nodule measuring on US greater than or equal to 10 mm in three orthogonal dimensions,
* less than 30% of the targeted nodule comprising cystic area,
* HIFU accessibility of the targeted nodule (distance between the skin and the anterior surface of the nodule less than 17 mm, with no interference of the collarbone with HIFU unit movements)
* normal thyrotropin concentration and
* absence of vocal cord immobility at laryngoscopy.

Exclusion Criteria:

* head and/or neck disease preventing hyperextension of the neck,
* history of thyroid cancer or other malignant tumors in the neck region,
* history of neck irradiation,
* intranodular macrocalcifications inducing a shadow substantial enough to preclude treatment with HIFU,
* nodules next to the posterior margin of the thyroid lobe with anteroposterior diameter less than 15 mm,
* pregnancy or lactation,
* any contraindication related to intravenous moderate sedation in the first HIFU treatment.

Primary outcomes:
measure: Change in thyroid nodule volume (mL)
timeFrame: 6 months
Secondary outcomes:
measure: The efficacy of reapplication HIFU after the first single session in 6 months
timeFrame: 6 months
measure: The safety of reapplication HIFU after the first single session in 6 months
timeFrame: 6 months
measure: The rate of vocal cord palsy in reapplication HIFU after the first single session in 6 months
timeFrame: 6 months
measure: The cosmetic score (in 0-10) of reapplication HIFU after the first single session in 6 months
timeFrame: 6 months
measure: The pain score (in 0-10) of reapplication HIFU after the first single session in 6 months
timeFrame: 6 months
measure: The satisfactory (in 0-10) of reapplication HIFU after the first single session in 6 month
timeFrame: 6 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
affiliation: The University of Hong Kong
name: Hung Hin, Brian Lang, MBBS (Hons)
role: PRINCIPAL_INVESTIGATOR
References:
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