Thyroid Associated Orbitopathy Treatment by Methotrexate Against Triamcinolone Periocular Injections

Overview

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.

Full Title of Study: “Comparative Study on the Efficacy of Periocular Methotrexate Versus Periocular Triamcinolone Injections in Management of Thyroid Associated Orbitopathy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: July 1, 2022

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

Interventions

  • Drug: Methotrexate
    • Three periocular injections of methotrexate at week 0, week 3 and week 6.
  • Drug: Triamcinolone Acetonide
    • Three periocular injections of triamcinolone acetonide at week 0, week 3 and week 6.

Arms, Groups and Cohorts

  • Experimental: Methotrexate
    • Periocular injections of methotrexate
  • Active Comparator: Triamcinolone acetonide
    • Periocular injections of triamcinolone acetonide

Clinical Trial Outcome Measures

Primary Measures

  • Change in CAS
    • Time Frame: 2 weeks, 1 month, 3 months and 6 months
    • Mean change in clinical activity score from baseline

Secondary Measures

  • Change in proptosis
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Cairo University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Islam Youssef Swaify, AL. – Cairo University
  • Overall Official(s)
    • Haytham E. Nasr, Study Chair, Cairo University
    • Rania A. El Essawy, Study Director, Cairo University
    • Kareem B. Elessawy, Study Director, Cairo University
    • Islam Y. Swaify, Principal Investigator, Cairo University

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