Clinical trial NCT02089542: Intra-operative Infra-red Fluorescent Imaging in Thyroid and Parathyroid Surgery
Official title: Development of a Clinical Protocol to Use Intra-operative Near Infra-red Fluorescent Imaging in Thyroid and Parathyroid Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Total Thyroidectomy
Bilateral Neck Exploration for Primary Hyperparathyroidism
Keywords: thyroidectomy
parathyroid surgery
parathyroid identification
methylene blue
near infrared fluorescence
intraoperative imaging
Lead sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
Sponsor class: OTHER
First posted: 2014-03-17
Enrollment: 41
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: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Optimum dose of Methylene Blue
timeFrame: 20 minutes
Secondary outcomes:
measure: Time to peak fluorescence
timeFrame: 20 minutes
Other outcomes:
measure: Postoperative calcium status
timeFrame: up to 12 weeks of surgery
measure: Serious adverse event
timeFrame: up to 30 days after surgery
Locations:
city: Sheffield
country: United Kingdom
facility: Department of General Surgery
state: South Yorkshire
Study officials:
affiliation: University of Sheffield
name: Saba Balasubramanian, MS FRCS PhD
role: PRINCIPAL_INVESTIGATOR
References: