Thyroid Associated Orbitopathy Treatment by Methotrexate Against Triamcinolone Periocular Injections (TOMATO)

Comparative Study on the Efficacy of Periocular Methotrexate Versus Periocular Triamcinolone Injections in Management of Thyroid Associated Orbitopathy

The study objective is to investigate the efficacy and safety of periocular injections of methotrexate in management of patients with active moderate to severe thyroid associated orbitopathy in comparison to periocular injections of triamcinolone acetonide.

Study Overview

• Status: Completed
• Conditions: Thyroid Associated Orbitopathy
• Intervention / Treatment: Drug: Methotrexate; Drug: Triamcinolone Acetonide

Detailed Description

Recruited subjects will be randomized such that one orbit receives 3 periocular injections of methotrexate and the contralateral orbit receives 3 periocular injections of triamcinolone acetonide at day 0, week 3 and week 6. All study subjects will be followed up for 6 months where outcome measures are assessed at 2 weeks, 1month, 3 months and 6 months after last injection

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Cairo university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Bilateral moderate to severe thyroid associated orbitopathy.
2. Clinical Activity score (CAS) ≥ 3.
3. Duration of thyroid associated orbitopathy < 2 years

Exclusion Criteria:

1. Sight threatening thyroid associated orbitopathy (dysthyroid optic neuropathy or exposure keratopathy) in any eye.
2. Glaucoma patients or those known to be steroid responders
3. Presence of orbital infections or any infection in nearby structures as paranasal sinusitis or dental abscess
4. Pregnancy
5. Previous orbital or lid surgeries
6. History of steroid therapy (oral, intravenous or periocular) or other immunosuppressive therapy within the previous 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Methotrexate; Periocular injections of methotrexate	Drug: Methotrexate; Three periocular injections of methotrexate at week 0, week 3 and week 6.
Active Comparator: Triamcinolone acetonide; Periocular injections of triamcinolone acetonide	Drug: Triamcinolone Acetonide; Three periocular injections of triamcinolone acetonide at week 0, week 3 and week 6.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in clinical activity score (CAS)	Mean change in clinical activity score from baseline. CAS is a 10-point score (0-10) with disease considered active if CAS is >3.	2 weeks, 1 month, 3 months and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in proptosis	Mean change in proptosis measured in millimeters by an exopthalmometer compared to baseline proptosis	2 weeks, 1 month, 3 months and 6 months
Change in lid aperture	Mean change in lid aperture (distance between upper and lower lid margin measured in millimeters by a ruler	2 weeks, 1 month, 3 months and 6 months
Percentage of overall responders	A participant is considered an overall responder if 2 or more of the following: Improvement of CAS ≥ 2 points.; Improvement of proptosis ≥ 2 mm.; Improvement of lid aperture ≥ 2 mm.; Improvement of soft tissue signs ≥ 1 grade; Improvement of EOM ductions	3 months and 6 months

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Chair: Haytham E. Nasr, Cairo university; Study Director: Rania A. El Essawy, Cairo university; Study Director: Kareem B. Elessawy, Cairo university; Principal Investigator: Islam Y. Swaify, Cairo university

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): July 15, 2022

Study Registration Dates

• First Submitted: June 18, 2022
• First Submitted That Met QC Criteria: June 18, 2022
• First Posted (Actual): June 23, 2022

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 17, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Methotrexate; Triamcinolone; Thyroid associated orbitopathy; Grave's orbitopathy; Periocular injections
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Graves Ophthalmopathy; Thyroid Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Triamcinolone; Methotrexate; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate
• Other Study ID Numbers: MD-139-2020

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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