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

NCT07762105 | Not Yet Recruiting Phase 1

• 1 other identifier: KE/FK/0253/EC/2025
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Thyroid Eye Disease; Graves Ophthalmopathy; Graves Orbitopathy

Keywords

graves orbitopapathy; thyroid eye disease; atorvastatin; statins; methylprednisolone; randomised controlled trial; orbital computed tomography; microRNA; graves ophthalmopathy

Outcome Measures

Primary Outcomes (1)

• Individual rectus muscle diameters

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

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

Secondary Outcomes (9)

• Composite ocular response

  At Week 24th

• Clinical activity score

  Baseline and every study visit to week 24

• Exophthalmos, clinical

  Baseline and every study visit to week 24

• Exophthalmos, radiological

  Baseline, weeks 12, 24

• Vertical palpebral fissure height

  Baseline and every study visit to week 24

Study Arms (2)

Methylprednisolone only

ACTIVE COMPARATOR

Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg per weeks for following six weeks

Drug: methylprednisolone (IVMP)

Methylprednisolone plus Atorvastatin

EXPERIMENTAL

Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg combined per week for following six weeks combined atorvastatin 20 mg per weeks for six months

Drug: Atorvastatin; Drug: methylprednisolone (IVMP)

Interventions

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 plus Atorvastatin

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)

Methylprednisolone only; Methylprednisolone plus Atorvastatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Banu Aji Dibyasakti: lead

Study Sites (1)

Universitas Gadjah Mada

Yogyakarta, Yogyakarta, Indonesia, Indonesia

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

Atorvastatin; Methylprednisolone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Banu Aji Dibyasakti, MD

CONTACT

+628112574789; bdibyasakti@gmail.com

Nikolaus Erik Darmawan, MD

CONTACT

+6281392133296; nikolauserikd7@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle investigator

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 13, 2026
• Study Start (Estimated): August 30, 2026
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: August 13, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)