Total Thyroidectomy Versus Thionamides in Patients With Moderate-to-Severe Graves' Ophthalmopathy

Prospective Randomized Clinical Trial of Total Thyroidectomy (Tx) Versus Thionamides (Anti-Thyroid Drugs) in Patients With Moderate-to-Severe Graves' Ophthalmopathy - a 1-year Follow-up

Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO.

Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months.

Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

Study Overview

• Status: Unknown
• Conditions: Graves Ophthalmopathy; Graves Disease; Graves' Ophthalmopathy Worsened
• Intervention / Treatment: Drug: Antithyroid Drug; Procedure: Total thyroidectomy

Detailed Description

Introduction: Graves disease (GD) is characterized by thyrotoxicosis and goiter, arising through circulating autoantibodies that bind to and stimulate the thyroid hormone receptor (TSHR). Graves' ophthalmopathy (GO) is characterized by inflammation, expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered: anti-thyroid drugs (ATD) (thionamides), radioactive iodine (RAI) and total thyroidectomy (Tx). There is currently no consensus on the treatment of Grave's disease and GO.

Objective: To examine the difference in the outcome of GO in patients with moderate-to-severe GO, who receive Tx versus further ATD after suffering their first relapse of GO or in which GO stays the same following the initial decrease in ATD therapy after 6 months.

Methods: This prospective randomized clinical trial with observer blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: CAScore/NOSPECS score, superonasal index measurements via ultrasound and quality of life score.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Surgery and Department of Ophthalmology Medical University Vienna
    • Contact: Lindsay Brammen, MD; Phone Number: +4314040056210; Email: lindsay.brammen@meduniwien.ac.at
    • Contact: Philipp Riss, MD; Phone Number: +4314040056210; Email: philipp.riss@meduniwien.ac.at
    • Principal Investigator: Philipp Riss, MD
    • Principal Investigator: Guido Dorner, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. GD and GO onset < 12 months
2. no previous GD treatment other than antithyroid drugs (ATD)
3. first relapse after decrease of antithyroid medication within 4-6 months
4. GO treatment with glucocorticoids based on the Kahaly scheme
5. patients under ATD with normal thyroid function or subclinical hyperthyroid function and moderate-to-severe GO
6. clinically active inflammation according to CAScore (>3/7)
7. informed consent

Exclusion Criteria:

1. GD and GO onset > 12 months
2. more than one relapse of GO longer than 6 months from diagnosis
3. previous GD treatment by RAI or surgery
4. SNI greater than 7.0
5. urgent orbital decompression surgery
6. loss of vision
7. loss of visual field
8. loss of color vision
9. patients not receiving glucocorticoids for GO
10. cytological findings of postsurgical histopathological results suspicious for malignancy
11. pregnancy or breast-feeding
12. contraindication to GC
13. halt of GC therapy
14. Patients with diabetes mellitus
15. age below 18 years
16. no informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Thyroidectomy; Total thyroidectomy	Drug: Antithyroid Drug; Antithyroid drug; Other Names: Thiamazol; Propylthiouracil
ACTIVE_COMPARATOR: Antithyroid drug; Thiamazol, Propylthiouracil	Procedure: Total thyroidectomy; Operation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle index (MI) from ultrasound measurements	Muscle index (MI) from ultrasound measurements	12 months
Thyroid antibodies	Thyroid antibodies	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CAScore/NOSPECS score	CAScore/NOSPECS score	12 months
Superonasal index measurements via ultrasound	Superonasal index measurements via ultrasound	12 months
Quality of life score	Quality of life score	12 months

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Philipp Riss, MD, Medical University Vienna; Principal Investigator: Guido Dorner, MD, Medical University Vienna

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): March 1, 2017
• Primary Completion (ANTICIPATED): February 1, 2019
• Study Completion (ANTICIPATED): June 1, 2019

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: February 22, 2017
• First Posted (ACTUAL): February 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 22, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Eye Diseases; Graves Ophthalmopathy; Graves Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Propylthiouracil; Antithyroid Agents
• Other Study ID Numbers: 1839/2015; 2015-003515-38 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No