Thyroid Eye DiseasePhase 1SEMAR-TEDNCT07762105
Study of Atorvastatin and Its Effects in Clinical and Radiological Aspects in Patients With Moderate-to-Severe Thyroid Eye Disease
A Phase 1 study testing Atorvastatin and methylprednisolone (IVMP) in people with Thyroid Eye Disease and Graves Ophthalmopathy, run by Banu Aji Dibyasakti at 1 site in Indonesia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Thyroid Eye Disease, Graves Ophthalmopathy, Graves Orbitopathy
- What is being tested?
- Atorvastatin and methylprednisolone (IVMP)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteIndonesia
- Study dates
- 30 Aug 2026to 30 Sep 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Indonesia1 site
Universitas Gadjah Mada
Yogyakarta, Yogyakarta, Indonesia
Banu Aji Dibyasakti, MD, +628112574789, bdibyasakti@gmail.com
Nikolaus Erik Darmawan, MD, +6281392133296, nikolauserikd7@gmail.com
About this study
Official 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
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.
- Being tested
- Atorvastatin, methylprednisolone (IVMP)
- Keywords
- graves orbitopapathy, thyroid eye disease, atorvastatin, statins, methylprednisolone, randomised controlled trial, orbital computed tomography, microRNA, graves ophthalmopathy
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
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)
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Atorvastatin; Drug: methylprednisolone (IVMP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Individual rectus muscle diameters
The primary outcome is measuring the rectus muscle diameters using Coronal CT, per muscle, both orbits
Measured: At the first week,12th week, and 24th week from starting point of treatment
Secondary outcomes (9)
Composite ocular response
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.
Measured: At Week 24th
Clinical activity score
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
Measured: Baseline and every study visit to week 24
Exophthalmos, clinical
Measurement of clinic exophthalmos using Hertel exophthalmometer, fixed base setting, single masked assessor
Measured: Baseline and every study visit to week 24
Exophthalmos, radiological
Exophthalmos measured from Interzygomatic line to posterior corneal surface, axial CT
Measured: Baseline, weeks 12, 24
Vertical palpebral fissure height
Palpbral fissure height measured using millimetre ruler, primary position of gaze, masked assessor
Measured: Baseline and every study visit to week 24
Change in LDL cholesterol
Using the Enzymatic colorimetric assay; used in the prespecified mediation analysis
Measured: Baseline, weeks 12, 24
Orbital fat volume
Using Segmentation at -200 to -30 HU, ITK-SNAP v4.2.0
Measured: Baseline, weeks 12, 24
Transcript levels in peripheral blood
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
Measured: Baseline, weeks 12, 24
Transcript levels in orbital tissue
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
Measured: At decompression 24th week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2026
- Study start30 Aug 2026 (estimated)
- Primary completion30 Jul 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Eye DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Banu Aji Dibyasakti
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Banu Aji Dibyasakti, Gadjah Mada University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07762105
- Sponsor's protocol ID
- KE/FK/0253/EC/2025
- Acronym
- SEMAR-TED
- Status last verified
- Aug 2026
- First submitted
- 30 Jul 2026
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: To keep the privacy of participants information
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07762105
- Acronym / sponsor ID
- SEMAR-TED / KE/FK/0253/EC/2025
- Keywords
- graves orbitopapathy, thyroid eye disease, atorvastatin, statins, methylprednisolone, randomised controlled trial, orbital computed tomography, microRNA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Banu Aji DibyasaktiUniversity, hospital or other
- Study start
- 30 Aug 2026 (estimated)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 13 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylprednisolone only | Active comparator | Drug: methylprednisolone (IVMP)Experimental group recieve methylprednisolone injection 500 mg per week for six weeks followed by methylprednisolone 250 mg per weeks for following six weeks |
| Methylprednisolone plus Atorvastatin | Experimental | Drug: Atorvastatin, Drug: methylprednisolone (IVMP)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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtorvastatinModerate-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. | Drug | Methylprednisolone plus Atorvastatin |
| methylprednisolone (IVMP)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) | Drug | Methylprednisolone only, Methylprednisolone plus Atorvastatin |
Primary outcome
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
9 secondary outcomes
Composite ocular response
Time frame: At Week 24th
Clinical activity score
Time frame: Baseline and every study visit to week 24
Exophthalmos, clinical
Time frame: Baseline and every study visit to week 24
Exophthalmos, radiological
Time frame: Baseline, weeks 12, 24
Vertical palpebral fissure height
Time frame: Baseline and every study visit to week 24
Change in LDL cholesterol
Time frame: Baseline, weeks 12, 24
Orbital fat volume
Time frame: Baseline, weeks 12, 24
Transcript levels in peripheral blood
Time frame: Baseline, weeks 12, 24
Transcript levels in orbital tissue
Time frame: At decompression 24th week
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
- Individual participant dataSharing planned: No. To keep the privacy of participants information
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atorvastatin and methylprednisolone (IVMP) in people with Thyroid Eye Disease and Graves Ophthalmopathy, run by Banu Aji Dibyasakti at 1 site in Indonesia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 13 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Indonesia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Banu Aji Dibyasakti, MD (+628112574789, bdibyasakti@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Individual rectus muscle diameters (time frame: At the first week,12th week, and 24th week from starting point of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2026.