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

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ClinicalTrials.gov Identifier: NCT02089542
Recruitment Status : Completed
First Posted : March 17, 2014
Last Update Posted : November 2, 2016
Sponsor:
Information provided by (Responsible Party):
Sheffield Teaching Hospitals NHS Foundation Trust

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.


Condition or disease Intervention/treatment Phase
Total Thyroidectomy Bilateral Neck Exploration for Primary Hyperparathyroidism Other: MB and fluorescent imaging Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Development of a Clinical Protocol to Use Intra-operative Near Infra-red Fluorescent Imaging in Thyroid and Parathyroid Surgery
Study Start Date : October 2014
Actual Primary Completion Date : June 2016
Actual Study Completion Date : October 2016


Arm Intervention/treatment
Experimental: 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
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
Other Names:
  • Methylthioninium chloride
  • Fluobeam 700 near infra-red imaging device




Primary Outcome Measures :
  1. Optimum dose of Methylene Blue [ Time Frame: 20 minutes ]
    Determine optimum dose of Methylene Blue that will enable fluorescence to be detected from the soft tissue structures in the neck


Secondary Outcome Measures :
  1. Time to peak fluorescence [ Time Frame: 20 minutes ]
    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.


Other Outcome Measures:
  1. Postoperative calcium status [ Time Frame: up to 12 weeks of surgery ]
  2. Serious adverse event [ Time Frame: up to 30 days after surgery ]

    This will include any one of the following:

    1. Death
    2. A life-threatening adverse event
    3. Inpatient hospitalisation or prolongation of existing hospitalisation
    4. A disability / incapacity
    5. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02089542


Locations
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United Kingdom
Department of General Surgery
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Sponsors and Collaborators
Sheffield Teaching Hospitals NHS Foundation Trust
Investigators
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Principal Investigator: Saba Balasubramanian, MS FRCS PhD University of Sheffield
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Responsible Party: Sheffield Teaching Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT02089542    
Other Study ID Numbers: STH17176
First Posted: March 17, 2014    Key Record Dates
Last Update Posted: November 2, 2016
Last Verified: November 2016
Keywords provided by Sheffield Teaching Hospitals NHS Foundation Trust:
thyroidectomy
parathyroid surgery
parathyroid identification
methylene blue
near infrared fluorescence
intraoperative imaging
Additional relevant MeSH terms:
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Hyperparathyroidism
Hyperparathyroidism, Primary
Parathyroid Diseases
Endocrine System Diseases
Methylene Blue
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action