TOMATO: Thyroid Associated Orbitopathy Treatment by Methotrexate Against Triamcinolone Periocular Injections

Sponsor

Cairo University (Other)

Overall Status

Completed

CT.gov ID

NCT05429450

Collaborator

(none)

Enrollment

Location

Arms

24.4

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Thyroid Associated Orbitopathy	Drug: Methotrexate Drug: Triamcinolone Acetonide	Phase 2

Detailed Description

Thyroid associated orbitopathy (TAO) is an autoimmune inflammatory disorder affecting the orbit in variable degrees resulting in a wide spectrum of clinical manifestations of varying severity. Common clinical manifestations include eyelid retraction (90%), exophthalmos (60%) and restricted extraocular motility (40%).

Despite being the only widely accepted effective therapy for active TAO, about 20-30% of patients may not respond adequately to corticosteroids. Another drawback is the tendency of TAO to relapse upon dose reduction or premature discontinuation of treatment. In addition, long term use of corticosteroids is associated with significant systemic adverse effects as well as ocular complications.

Other alternative treatments including immunosuppressives as mycophenolate and methotrexate or biologics as teprotumumab and rituximab have been suggested for use as steroid sparing agents or in steroid resistant patients.

In order to avoid the drawbacks associated with systemic use of corticosteroids or immunosuppressives, the periocular route of drug delivery has been resorted to with the aim of delivering the therapeutic dose to the target orbital tissue while minimizing the unwanted systemic exposure. Periocular administration of corticosteroids for management of active TAO has been evaluated in many studies, however the efficacy of periocular administration of other immunosuppressive in management of TAO haven't be assessed.

The aim of this prospective interventional double-blind randomized controlled study is to assess the efficacy and safety of periocular injections of methotrexate in the management of active, moderate to severe TAO in comparison to periocular injections of triamcinolone acetonide.

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2020

Actual Primary Completion Date :

Jul 1, 2022

Actual Study Completion Date :

Jul 15, 2022

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Change in proptosis [2 weeks, 1 month, 3 months and 6 months]
Mean change in proptosis measured in millimeters by an exopthalmometer compared to baseline proptosis
Change in lid aperture [2 weeks, 1 month, 3 months and 6 months]
Mean change in lid aperture (distance between upper and lower lid margin measured in millimeters by a ruler
Percentage of overall responders [3 months and 6 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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