Intra-operative Infra-red Fluorescent Imaging in Thyroid and Parathyroid Surgery

Total Thyroidectomy Clinical Trial

Official title:

Development of a Clinical Protocol to Use Intra-operative Near Infra-red Fluorescent Imaging in Thyroid and Parathyroid Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02089542
• Other study ID #: STH17176
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 13, 2014
• Last updated: November 1, 2016
• Start date: October 2014
• Est. completion date: October 2016

Study information

• Verified date: November 2016
• Source: Sheffield Teaching Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

Reliable identification of parathyroid glands is critical to the success of thyroid and parathyroid surgery. In thyroid surgery, inadvertent injury to parathyroid glands may cause temporary or permanent hypoparathyroidism (low calcium levels needing long term treatment). In parathyroid surgery, early identification of normal and/or enlarged parathyroid glands helps in deciding on the extent of surgery and increases the chances of postoperative normal calcium levels.

Methylene Blue (Methylthioninium chloride, MB) is a dye that when given intravenously in high doses, is taken up differently by thyroid and parathyroid tissue. It is currently used during parathyroid surgery by some surgeons to help identify enlarged parathyroid glands by visual examination alone. Such visual examination is unhelpful in the identification of 'normal' parathyroid tissue. MB exhibits fluorescent properties in the near-infrared range (light just beyond the visible spectrum). This can be picked up by an appropriate imaging system. This has potential to identify and differentiate between 'normal' parathyroid, 'abnormal' parathyroid and thyroid tissue during surgery.

The investigators have established the feasibility of the intra-operative use of a near infra-red fluorescent imaging device called Fluobeam® and demonstrated the ability of this device to pick up near infra-red fluorescence from human tissue after administration of intravenous MB. Animal experiments have shown that doses as low as 0.1mg/kg of MB given intravenously enable fluorescent visualisation of thyroid and parathyroid glands.

This study will aim to optimise the dose and timing of administration of MB in human thyroid and parathyroid surgery and to develop a protocol which would then subsequently be assessed for effectiveness in a multi-centred randomized controlled setting.

Description:

Around 13,000 thyroid and parathyroid operations are performed per year in England for both benign and malignant disease. Reliable identification of parathyroid glands is critical to the success of thyroid and parathyroid surgery. In thyroid surgery, inadvertent injury to parathyroid glands may cause temporary or permanent hypoparathyroidism (low calcium levels needing long term treatment); the latter is associated with significant long term problems. In parathyroid surgery, early identification of normal and/or enlarged parathyroid glands helps in deciding on the extent of surgery and increases the chances of postoperative normal calcium levels.

Methylene Blue (Methylthioninium chloride, MB) is a dye that when given intravenously in high doses, is taken up differently by thyroid and parathyroid tissue. It is currently used during parathyroid surgery by some surgeons to help identify enlarged parathyroid glands by visual examination alone. At these doses, there is a risk of adverse effects from administration of MB. Such visual examination is unhelpful in the identification of 'normal' parathyroid tissue. MB is not currently used in surgery for thyroid pathologies. MB exhibits fluorescent properties in the near-infrared range (light just beyond the visible spectrum). This can be picked up by an appropriate imaging system. This has potential to identify and differentiate between 'normal' parathyroid, 'abnormal' parathyroid and thyroid tissue during surgery.

The investigators have established the feasibility of the intra-operative use of a near infra-red fluorescent imaging device called Fluobeam® and demonstrated the ability of this device to pick up near infra-red fluorescence from human tissue after administration of intravenous MB. Animal experiments have shown that doses as low as 0.1mg/kg of MB given intravenously enable fluorescent visualisation of thyroid and parathyroid glands.

This study will aim to optimise the dose and timing of administration of MB in human thyroid and parathyroid surgery and to develop a protocol which would then subsequently be assessed for effectiveness in a multi-centred randomized controlled setting.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: October 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

-All patients undergoing either a total thyroidectomy or bilateral neck exploration for PHPT in Sheffield Teaching Hospitals NHS Foundation Trust

Exclusion Criteria:

• Patients undergoing re-do procedures

• Patients unable to understand spoken and written English

• Patients unable to give adequate informed consent

• Patients with a history of intolerance or sensitivity to MB

• Patients with known G6PD deficiency

• Patients on serotonin reuptake inhibitors

• Patients undergoing surgery for thyroglossal cyst and

• Patients undergoing thoracic exploration; either alone or in combination with a neck exploration

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bilateral Neck Exploration for Primary Hyperparathyroidism
• Hyperparathyroidism
• Hyperparathyroidism, Primary
• Total Thyroidectomy

Intervention

Other:
• MB and fluorescent imaging
Single arm study for the development of a protocol stipulating the optimum dose and time to peak near infra-red fluorescence from intraoperative injection of low dose Methylthioninium chloride

Locations

Country	Name	City	State
United Kingdom	Department of General Surgery	Sheffield	South Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Sheffield Teaching Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Postoperative calcium status		up to 12 weeks of surgery	No
Other	Serious adverse event	This will include any one of the following: Death; A life-threatening adverse event; Inpatient hospitalisation or prolongation of existing hospitalisation; A disability / incapacity; A congenital anomaly in the offspring of a participant The reporting period for Serious Adverse Events will be from the time of induction of anaesthetic until 30 days after the day of surgery. Important medical events that may not result in death, be life-threatening, or require hospitalisation may be considered a serious adverse event when, based upon appropriate medical judgment, they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. All adverse events will be assessed for seriousness, expectedness and causality.	up to 30 days after surgery	Yes
Primary	Optimum dose of Methylene Blue	Determine optimum dose of Methylene Blue that will enable fluorescence to be detected from the soft tissue structures in the neck	20 minutes	No
Secondary	Time to peak fluorescence	Time to peak fluorescence at varying doses of Methylene Blue will be assessed during the observation period, which will be a maximum of twenty minutes.	20 minutes	No