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

NCT ID: NCT02089542

Last Updated: 2016-11-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-31
• Study Completion Date: 2016-10-31

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.

Conditions

Total Thyroidectomy; Bilateral Neck Exploration for Primary Hyperparathyroidism

Keywords

thyroidectomy; parathyroid surgery; parathyroid identification; methylene blue; near infrared fluorescence; intraoperative imaging

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

MB and fluorescent imaging

Intervention Type: OTHER

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

Interventions

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

Intervention Type: OTHER

Other Intervention Names

Methylthioninium chloride; Fluobeam 700 near infra-red imaging device

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sheffield Teaching Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Saba Balasubramanian, MS FRCS PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sheffield

Locations

Department of General Surgery

Sheffield, South Yorkshire, United Kingdom

Countries

United Kingdom

Other Identifiers

STH17176

Identifier Type: -

Identifier Source: org_study_id