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

Phase 1Not Yet RecruitingNCT07762105

Banu Aji Dibyasakti64 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Thyroid Eye Disease Graves Ophthalmopathy Graves Orbitopathy

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Individual rectus muscle diameters

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

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

Secondary Outcomes

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: 1. reduction in clinical activity score of 2 points or more; 2. reduction in proptosis of 2 mm or more, without an increase of 2 mm or more in the fellow eye; 3. reduction in vertical palpebral fissure height of 2 mm or more, with the same proviso for the fellow eye; 4. disappearance of diplopia, or improvement by at least one Gorman grade; 5. 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.

Time frame: 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

Time frame: Baseline and every study visit to week 24

Exophthalmos, clinical

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

Time frame: Baseline and every study visit to week 24

Exophthalmos, radiological

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

Time frame: Baseline, weeks 12, 24

Vertical palpebral fissure height

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

Time frame: Baseline and every study visit to week 24

Change in LDL cholesterol

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

Time frame: Baseline, weeks 12, 24

Orbital fat volume

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

Time frame: 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

Time frame: 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

Time frame: At decompression 24th week

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts