Clinical trial NCT02658552: A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Benign Thyroid Nodules
Official title: A Prospective Evaluation of High Intensity Focused Ultrasound (HIFU) in the Treatment of Benign Thyroid Nodules
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Benign Thyroid Nodules
Keywords: HIFU
Benign thyroid nodule
Low risk
New treatment
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2016-01-20
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the short-term efficacy of high intensity focused ultrasound (HIFU) in the treatment of benign thyroid nodules

Detailed description: Background:

Thyroid nodules are very common worldwide. In an iodine-replete population like Hong Kong, the estimated prevalence of a clinically palpable thyroid nodule, is close to 5% while the prevalence of ultrasonically detectable nodules could be up to 67%. With the frequent use of computed tomography, carotid ultrasound studies and positron emission scans nowadays, many small, non-palpable thyroid nodules are incidentally detected. The use of high intensity focused ultrasound MRI guided or ultrasound guided have been used to treat different types of soft tissue cancer like prostate cancer, liver cancer and breast cancer. This device has been tried in a clinical study where patients with thyroid nodules, who were already scheduled for thyroidectomy, were treated using HIFU in order to evaluate the safety and feasibility of the device and to better determine the treatment parameters and effect.

The results showed that the overall safety of the treatment was satisfactory and the lesions produced by the HIFU shots in the nodule were precise. This pilot study was extended to a clinical trial where patients with a benign thyroid nodule were treated. Twenty-one patients were treated in this study versus 11 controls. No serious adverse events (SAE) have occurred. A patient with a toxic thyroid nodule was also treated with the HIFU device (Theraclion, France). The treatment was well tolerated and biologic euthyroidism was achieved at 3 months (TSH, 1.91 mIU/L) and was maintained at 6, 12, and 18 months. At 12 and 18 months, the treated nodule was barely seen as a nonvascularized hypoechoic scar. Thyroid scintigraphy showed a recovery of the thyroid iodine uptake.

Since November 1st 2007, this HIFU device (Theraclion, France) has been CE marked for HIFU treatment of neck pathologies. 11 patients with primary hyperparathyroidism have been treated and followed. The mean follow-up is 9.5 months (1-28 months).

Symptomatic hypocalcaemia was not observed in any patient after HIFU treatments or during follow-up. A prospective monocenter study was performed in Bulgaria for the treatment of benign solid thyroid nodule by US-Guided HIFU. Twenty thyroid nodules were treated during one HIFU session. The mean ± standard deviation nodule volume was 4.96 mL ± 2.79 at the start of the study. Nodule volume had decreased to 3.05 mL ±1.96 at the 3-month follow-up examination (n = 20, P \< .001), and reached 2.91 mL ± 2.43 by the 6-month follow-up examination (n = 16, P \< .001). By then, the mean volume reduction was 48.7% ± 24.3 (P\< .001). Minor transient complications such as subcutaneous edema and mild skin redness were observed in two patients. Another monocenter study was performed in Germany in 2014. Ten patients with one thyroid nodule each were treated by HIFU. Three months after the procedure, thyroid nodule volume was significantly reduced by 48.8% (median) and a shrinkage up to 75% of the volume was observed. In terms of safety, no serious side effect related to the procedure was reported.

Objectives:

The present study is aimed to explore the followings:

1. To evaluate the efficacy of the HIFU for the treatment of benign thyroid nodules using assessment of patient experience and adverse event reporting.
2. To evaluate the tolerance of HIFU in the treatment of benign thyroid nodules.
3. To determine the location parameters associated with optimal efficiency tissue ablation.

The procedure schedule comprises:

* An first visit (V0)
* The HIFU session (D0)
* A visit at 1, 3 and 7 days after HIFU session (D1, D3, D7)
* A visit at 3 and 6 months (M3, M6).
* At each visit: any local and/or general adverse event will be documented in case report form (CRF).

Ultrasound measurement of the treated nodule (in 3 dimensions) will be performed at each scheduled visit.

The treatment procedure of Echopulse consists of five treatment steps:

* Pre-treatment ultrasonography
* Positioning
* Planning
* Generation of HIFU treatment pulses in the volume defined above; power setting is achieved on regularly spaced sites subsets.
* Post-treatment visualization and final report. The parameters of HIFU treatment will be part of the clinical study data base. When an HIFU session is prematurely interrupted, the reason of interruption will be recorded in the CRF (adverse event, technical failure, others).

Study duration will lbe 6 months for each patient, counting from the post-HIFU day.

Eligibility criteria: Inclusion Criteria:

* Male or female patient 18 years or older.
* Patient presenting with at least one thyroid nodule with no signs of malignancy:

  1. Non suspicious clinically and at ultrasonography imaging
  2. Benign cytological diagnosis at fine needle aspiration biopsy in the last 6 months
  3. Normal serum calcitonin
  4. No history of neck irradiation
* Serum TSH and free T4 levels within the normal range
* Targeted nodule deemed to be accessible and eligible to HIFU
* Absence of vocal cord paresis at laryngoscopy
* Nodule greatest diameter between ≥10 - 20mm as measured by ultrasound
* Composition of the targeted nodule(s) : predominantly solid
* Patient is mentally competent and has given informed consent.

Exclusion Criteria:

* Head and/or neck disease that prevents extension of neck
* Known history of thyroid cancer or other malignant tumors in the neck region
* History of neck irradiation
* Intranodular macrocalcification inducing a shadow in the thyroid significant enough to preclude HIFU treatment
* A nodule next to the posterior margin of the lobe with distance \<15mm
* Pregnant or lactating woman
* Any contraindication to the assigned analgesia/anaesthesia.

Primary outcomes:
measure: The changing volume of benign thyroid nodule after HIFU treatment
timeFrame: 6 months
measure: The changing greatest dimension of benign thyroid nodule after HIFU treatment
timeFrame: 6 months
Secondary outcomes:
measure: The pain assessment (scoring 1-10) after treatment
timeFrame: 6 months
measure: Incidence of local/ or general adverse events
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
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