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NCT Number: NCT07762105

Study of Atorvastatin and Its Effects in Clinical and Radiological Aspects in Patients With Moderate-to-Severe Thyroid Eye Disease

The trial tests the hypothesis that, in adults with active, moderate-to-severe Graves' orbitopathy, 24 weeks of oral atorvastatin 20 mg daily added to a standard 12-week course of intravenous methylprednisolone produces a greater reduction in extraocular muscle size than intravenous methylprednisolone alone, and that any such reduction is accompanied by lower expression of TSH receptor, IGF-1 receptor, PDGF receptor, PI3K/AKT and miR-155 transcripts, and higher expression of miR-146a. The prespecified direction for miR-146a follows its reported suppression in CD4+ T cells in active disease [26]. Reported directions of change are compartment-specific and not unanimous, so the transcript analyses are exploratory.

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Key information

Conditions

Thyroid Eye Disease Autoimmune Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Endocrine System Diseases Exophthalmos Eye Diseases Eye Diseases, Hereditary Genetic Diseases, Inborn Goiter Graves Disease Graves Ophthalmopathy Graves Orbitopathy Hyperthyroidism Immune System Diseases Orbital Diseases Thyroid Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 to 75 years inclusive
  • Graves' orbitopathy graded moderate-to-severe by EUGOGO criteria
  • Active disease, clinical activity score ≥ 3 of 7
  • Rehabilitative orbital decompression anticipated after completion of glucocorticoid therapy, on the usual clinical grounds
  • Able to attend weekly infusion visits and complete follow-up to week 48
  • Written informed consent given
  • For women of childbearing potential, agreement to use effective contraception until week 24

Exclusion criteria

  • Sight-threatening disease at screening: dysthyroid optic neuropathy or corneal breakdown
  • Any other autoimmune disease requiring systemic immunosuppresion
  • Known hypersensitivity to atorvastatin or to any statin
  • Current or recent (within 3 months) use of any lipid-lowering drug
  • Any contraindication to orbital decompression
  • Any independent indication for lipid-lowering therapy: established atherosclerotic cardiovascular disease, more than one cardiovascular risk factor (diabetes mellitus, hypertension, obesity), or LDL cholesterol ≥ 190 mg/dL
  • Systemic glucocorticoid or immunosuppressive treatment for orbitopathy within the preceding 3 months
  • Previous orbital irradiation or orbital surgery
  • Alanine or aspartate aminotransferase > 3 × upper limit of normal, or creatine kinase > 5 × upper limit of normal, at screening
  • Estimated glomerular filtration rate < 30 mL/min/1.73 m²
  • Pregnancy at screening (confirmed by a negative test before randomisation) or breastfeeding
  • Concomitant treatment with a strong CYP3A4 inhibitor
  • Any condition that, in the opinion of the investigator, would prevent completion of the trial

Treatment and study plan

atorvastatin

Drug

Moderate-to-severe Graves' orbitopathy at a tertiary referral centre in Yogyakarta, Indonesia, will be allocated 1:1 to intravenous methylprednisolone (500 mg weekly for six weeks, then 250 mg weekly for six weeks) with oral atorvastatin 20 mg daily for 24 weeks.

methylprednisolone (IVMP)

Drug

Moderate-to-severe Graves' orbitopathy at a tertiary referral centre in Yogyakarta, Indonesia, will be allocated 1:1 to intravenous methylprednisolone (500 mg weekly for six weeks, then 250 mg weekly for six weeks)

Primary outcomes

  1. Individual rectus muscle diameters

    Time frame: At the first week,12th week, and 24th week from starting point of treatment

    The primary outcome is measuring the rectus muscle diameters using Coronal CT, per muscle, both orbits

Secondary outcomes

  1. Composite ocular response

    Time frame: At Week 24th

    A participant is a responder if at least two of the five criteria below are met in the more affected eye, with no deterioration in any of them in either eye:

    • reduction in clinical activity score of 2 points or more;
    • reduction in proptosis of 2 mm or more, without an increase of 2 mm or more in the fellow eye;
    • reduction in vertical palpebral fissure height of 2 mm or more, with the same proviso for the fellow eye;
    • disappearance of diplopia, or improvement by at least one Gorman grade;
    • improvement in best-corrected visual acuity of 0.1 logMAR or more, this being the step on the logMAR chart closest to the 0.2-decimal criterion used in STAGO.

  2. Clinical activity score

    Time frame: Baseline and every study visit to week 24

    7-item EUGOGO scale, masked assessor

    Score :

    • Minimum score 0 and maximum score 7 at first meeting
    • Maximum score 10 at follow up meeting Higher score has worse outcome

  3. Exophthalmos, clinical

    Time frame: Baseline and every study visit to week 24

    Measurement of clinic exophthalmos using Hertel exophthalmometer, fixed base setting, single masked assessor

  4. Exophthalmos, radiological

    Time frame: Baseline, weeks 12, 24

    Exophthalmos measured from Interzygomatic line to posterior corneal surface, axial CT

  5. Vertical palpebral fissure height

    Time frame: Baseline and every study visit to week 24

    Palpbral fissure height measured using millimetre ruler, primary position of gaze, masked assessor

  6. Change in LDL cholesterol

    Time frame: Baseline, weeks 12, 24

    Using the Enzymatic colorimetric assay; used in the prespecified mediation analysis

  7. Orbital fat volume

    Time frame: Baseline, weeks 12, 24

    Using Segmentation at -200 to -30 HU, ITK-SNAP v4.2.0

  8. Transcript levels in peripheral blood

    Time frame: Baseline, weeks 12, 24

    TSH-R, IGF-1R, PDGF-R, PI3K/AKT, miR-146a, miR-155; qRT-PCR, fold change relative to GAPDH for the messenger RNA targets and to U6 snRNA for the microRNA target

  9. Transcript levels in orbital tissue

    Time frame: At decompression 24th week

    TSH-R, IGF-1R, PDGF-R, PI3K/AKT, miR-146a, miR-155; qRT-PCR, fold change relative to GAPDH for the messenger RNA targets and to U6 snRNA for the microRNA targets; specimen taken at rehabilitative decompression

Study contacts

Contact information is provided by the study sponsor or research team.

Banu Aji Dibyasakti, MD

CONTACT

[email protected]

+628112574789

Nikolaus Erik Darmawan, MD

CONTACT

[email protected]

+6281392133296

Sponsors and collaborators

Lead sponsor

Banu Aji Dibyasakti

Other

Registry information

Official study title

Adjunctive Atorvastatin in Moderate-to-severe Thyroid Eye Disease (SEMAR-TED: Structural, Biomarker Expression and Muscle Endpoints of Atorvastatin): Study Protocol for a Randomised, Open-label, Assessor-masked Controlled Trial

Acronym: SEMAR-TED

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 13, 2026
Registry last updated
Aug 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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